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Project

Biomedical Research Center SAS

International Projects

A4L_ACTIONS - Alliance for Life Sciences: From Strategies to Actions in Central and Eastern Europe

Aliancia pre živé vedy: od stratégií k činom v strednej a východnej Európe

Duration: 1. 5. 2021 - 30. 4. 2024
Program: Horizont 2020
Project leader: prof. RNDr. Pastoreková Silvia DrSc.
Annotation:Research and innovation (R&I) plays a pivotal role in addressing Europe’s societal challenges including ensuring health and wellbeing of the citizens. Differences still persist in R&I performance between countries despite significant investments. In the health sector, the R&I gap can profoundly affect the quality of health and life of European citizens. Continuing the success of Alliance4Life, the EU-funded A4L_ACTIONS project aims to tackle the health R&I gap by improving the culture, governance, recognition and innovation potential of the health research-performing institutions in the lower-performing Central and Eastern European countries. This will help increase their attractiveness and pave the way for collaborations with advanced European countries.
Project web page:https://alliance4life.ceitec.cz

DE-PASS - DE-PASS Determinants of Physical Activities in Settings

DE-PASS Determinanty pohybovej aktivity v modernej spoločnosti

Duration: 22. 7. 2020 - 21. 4. 2024
Program: COST
Project leader: prof. MUDr. Ukropcová Barbara PhD.

Epigenotoxicity of nanomaterials

Epigenetická toxicita nanomateriálov

Duration: 1. 1. 2020 - 31. 12. 2022
Program: Medziakademická dohoda (MAD)
Project leader: RNDr. Gábelová Alena CSc.
Annotation:Progress in the field of material science and nanotechnology has opened the door for ground-breaking innovations in biomedicine and diverse industrial applications, some of which are closely linked with our everyday life. Nanotechnology provides great benefits; however, little is known as yet about the potential risks posed by nanomaterials (NMs) exposure to human health and to the environment. Numerous toxicology studies have demonstrated that NMs might possess serious risks to humans. On the other hand, epigenetic, disease-related consequences of exposure to nanomaterials are poorly understood. Epigenetic modifications, a non-genotoxic mechanism of toxicant-induced health effects, are significantly modulated by the long-term effects of environmental factors including NMs. Comprehensive assessment of epigenetic toxicity in vitro and in vivo therefore allows a more objective evaluation the NMs 'contribution' to development of multifactorial diseases or an increased incidence of cancer. Moreover, understanding the epigenetic effects of NMs can help to produce `safe by design` nanomaterials and avoid potential health hazard.

EVA-GLOBAL - European Virus Archive GLOBAL

Európsky vírusový archív GLOBAL

Duration: 1. 1. 2020 - 31. 12. 2023
Program: Horizont 2020
Project leader: RNDr. Klempa Boris DrSc.
Project web page:https://www.european-virus-archive.com/

TVISTOFF - Tick-Virus Interactions Shape persistence and Transmission OF Flavivirus pathogen in tick vector

Interakcie medzi kliešťom a vírusom ovplyvňujú perzistenciu a prenos vírusu kliešťovej encefalitídy v kliešťoch

Duration: 1. 9. 2021 - 31. 8. 2023
Program: Horizont 2020
Project leader: RNDr. Koči Juraj PhD.
Annotation:In Europe, tick-borne encephalitis virus (TBEV) causes tick-borne encephalitis, the most important viral life-threatening disease transmitted by ticks. Interactions among the virus, tick and host are inseparable and paramount for a successful circulation of TBEV in an enzootic cycle. Nevertheless, research in this area has predominantly focused on TBEV pathogenesis in vertebrate hosts. Limited knowledge on virus-tick interactions points out to lack of systematic studies and warrants research implementing novel virus-tick models. Therefore, the goal of this fellowship is to investigate the roles of molecular factors of TBEV virulence and tick neurosecretory compounds in adaptation and transmission of TBEV. The innovative concept involves a development of fluorescently labelled TBEV mutants by reverse genetics, implementation of host-free artificial membrane tick feeding system, and characterising components of tick neuroendocrine systems. The interdisciplinary approach of interconnecting the applicant's unique skills in tick physiology and bacterial tick-borne pathogens, expertise of the host group in arbovirology and capacity of partner group in physiology of tick neuroendocrine systems will be instrumental in widening knowledge on virus-tick interactions. Developed tools and obtained results will provide invaluable foundation for research of other neglected tick-borne viruses. Taking together, this fellowship will enable the applicant to reintegrate into the host organisation in his home country, to carry out innovative research, and ultimately to reach professional maturity as an independent investigator.

HF-MetaB - Metabolic therapy of heart failure: which role for B vitamins

Metabolická terapia srdcového zlyhania: úloha vitamínov B

Duration: 1. 4. 2020 - 31. 3. 2023
Program: ERANET
Project leader: RNDr. Zahradníková, ml. Alexandra PhD.
Annotation:Heart failure (HF) is a major cause of death worldwide. It is clear that profound modulations of energy metabolism are involved in the development of HF. This includes a drop in the cardiac levels of energy carrier compounds, ATP, Phosphocreatine, and nicotinamide adenine dinucleotide (NAD+), a major coenzyme in glycolysis and mitochondrial ATP generation. In this respect we previously showed, in a mouse model of cardiac pressure overload, the protective effect of diet supplementation with two vitamins (B12/B9) stimulating the mitochondrial biogenesis pathways, or with nicotinamide riboside (NR), a recently characterized vitamin B3 which is a NAD+ precursor. Inasmuch as these treatments were given before the appearance of the first symptoms of HF in these studies, we propose here to test the efficiency of a treatment with a cocktail of these 3 B vitamins in symptomatic HF in mice to propose an eventual curative use of these vitamins. Our primary aim will be to assess the impact of treatment on survival, exercise capacities, cardiac function, mitochondrial respiration and dynamics, calcium metabolism and metabolic fluxes. In a translational perspective toward clinics, we will also assess the impact of this vitamins B cocktail in the context of standard of care of HF (β-blocker, ACE inhibitor). Finally, it is critically important to consider the sex differences in treatment of HF. Therefore the second aim of the presented project is to compare the effect of the treatment in males and females that differ as regards alteration in mitochondrial and calcium metabolism in HF.

MEDBIODOSE - Molecular Markers for Biological Dosimetry in Radiation Oncology, Cancer Risk, Assesment and Optimizing Cancer Therapy

Molekulárne markery pre biologickú dozimetriu v radiačnej onkológii a hodnotenie rizika vzniku a optimalizácie liečby rakoviny

Duration: 19. 9. 2017 - 9. 7. 2023
Program: IAEA
Project leader: doc. Ing. Beliaev Igor DrSc.
Annotation:Cytogenetic analysis remains the only standard method for biological dosimetry. It is generally accepted that new molecular markers associated with biological dosimetry and cancer risks should be established and dependence of these risks on conditions of irradiation such as dose should be verified. Relevant cellular model systems are needed to verify and predict these risks. Hematopoietic stem cells (HSC) are the major target of leukemogenesis and also most relevant cellular model for assessing cancer risk associated with ionizing radiation. Usually, characteristic chromosomal translocations resulting in so-called preleukemic fusion genes (PFG) arise prenatally in HSC as a first key event in multistage process of leukemogenesis. DNA double-strand breaks (DSB) are critical DNA damage resulting in PFG. CD34+ HSC stem cells from umbilical cord blood (UCB) will be studied in comparison to lymphocytes. The project will focus on the low dose range (≤10 cGy) to which people is usually exposed in aircrafts during flights, at security controls (airports) and during medical investigations (such as computer tomography and mammography). The data will be also obtained in higher dose range to find out whether the low dose effects can be extrapolated from the higher doses. This project will validate possible molecular markers for estimation of low-dose effects in HSC and lymphocytes which may be used in biodosimetry and cancer epidemiological studies. Possible correlation of constitutive and induced DNA damage and apoptosis will be analyzed in hematopoietic cells of ALL and AML patients. The obtained data will be correlated with immunophenotype, presence of PFG and clinical outcome such as treatment response, minimal residual disease (MRD), risk group, side effects. If some correlations will be established it may provide new strategy for optimizing cancer therapy.
Project web page:https://www.iaea.org/newscenter/news/new-crp-applications-of-biological-dosimetry-methods-in-radiation-oncology-nuclear-medicine-diagnostic-and-interventional-radiology-e35010

Myokines and metabolically active molecules in the pathogenesis of idiopathic inflammatory myopathies

Myokíny a metabolicky aktívne molekuly v patogenéze idiopatických zápalových myopatií

Duration: 1. 5. 2021 - 31. 12. 2024
Program: Iné
Project leader: prof. MUDr. Ukropcová Barbara PhD.

UNMET - UNveiling the MEchanism(s) underlying the switch to mania during antidepressant treatment: The role of glutamate

Odkrytie mechanizmov zodpovedných prešmyk z depresie do mánie počas antidepresívnej liečby: úloha glutamátu

Duration: 1. 7. 2019 - 31. 8. 2023
Program: ERANET
Project leader: prof. PharmDr. Ježová Daniela DrSc.

SynaDev - Regulation of synaptic proteins in transgenic mouse model of neurodevelopmental disorder

Regulácia synaptických proteínov v transgénnom modeli vývinového ochorenia

Duration: 1. 1. 2020 - 31. 12. 2022
Program: Iné
Project leader: doc. RNDr. Bakoš Ján PhD.
Annotation:The heterogeneity and the progression of the neurodevelopmental disorders are associated with alterations in synaptic proteins. However specific developmental changes of the distribution of cell adhesion molecules and scaffolding proteins in relation to the pathology of Prader-Willi syndrome and Schaaf-Yang syndrome is not known. Therefore, the aim of the project is to analyze synaptic proteins and scaffolding proteins in various developmental stages of Magel2-deficient mice. French team created a Magel2-knockout mouse model and showed that the mutant pups suffer from lack of sucking initiation right after birth (in males and females) and show autistic behavior in adulthood. This model is widely accepted as a model of human Prader-Willi syndrome, in which Magel2 is deleted, and Schaaf-Yang syndrome, presenting point mutations of Magel2. Slovak research team together with French partners will closely collaborate to analyze synaptic proteins among them neurexins and neuroligins in various brain regions. Studying the role of synaptic proteins in the process of early brain maturation can reveal potential relationship between synaptic proteins and altered behavioral phenotype. We will bring relevant data on the role of synaptic proteins in the pathogenesis of disorders of the central nervous system.

RESCUER - Resistance under treatment in breast cancer

Rezistencia po liečbe u karcinómu prsníka

Duration: 1. 8. 2020 - 31. 5. 2024
Program: ERANET
Project leader: Mgr. Cihová Marína PhD.
Annotation:The concept behind this project is that by computational algorithms and mathematical modelling integrating data from clinical trials, ex vivo experimental models, and tumor molecular data at multiple levels will lead to the identification of drivers of resistance. These will be incorporated into patient-specific therapeutic regimens in a systems medicine approach. A leading edge of RESCUER is combining state-of-art mathematical modeling to data obtained from clinical trials and cutting-edge cell models to discover patientspecific therapeutic regimens. The efficacy in overcoming resistance will be evaluated by treating patient-derived xenograft (PDX) models derived from treatment resistant breast cancer (BC) patients prior to forthcoming clinical trials aimed to enroll patients with resistant tumors will be designed. The investigation and discovery of effective treatments for subclasses of BC can be performed only upon a deep understanding of intra-patient and inter-tumor heterogeneity and of the mechanisms of treatment resistance

RyRinHeart - RyRinHeart - Discovery of Ryanodine Receptor Inhibitors for Heart Diseases

RyRinHeart - Vývoj inhibítorov ryanodínového receptora pre srdcové ochorenia

Duration: 1. 1. 2020 - 31. 12. 2022
Program: Bilaterálne - iné
Project leader: Ing. Zahradníková Alexandra DrSc.
Annotation:Cardiac ryanodine receptors (RyR2) control the pumping function of the heart by regulating calcium release required for cardiac myocyte contraction. Many heart diseases are accompanied by disorders of calcium release. These disorders could be suppressed by drugs that prevent unwanted RyR2 activity. The aim of this project is to develop specific inhibitors, adapted to the structure of cardiac RyR2, with the potential to treat calcium handling disorders in heart disease. We will use our original knowledge of the structure of RyR2 to identify loci in the 3D-structure of RyR2 that reduce its activity by ligand binding. This will allow us to design and synthesize RyR2 inhibitors. We will test their efficacy in experiments monitoring RyR activity. The in situ efficacy of selected agents, most promising for regulation of RyR2 function, will be tested on isolated cardiac myocytes and finally on the hearts of healthy animals and animals with heart disease. Methodologically, the project is based on two pillars: molecular structure simulations, molecular dynamics, and computer-assisted drug design, the main body of expertise being the Turkish side, and a wide range of experimental and theoretical methods of studying ion channel function and calcium signalling (biochemical and electrophysiological methods, confocal microscopy, mathematical modelling of dynamics of intracellular processes), where expertise will be provided by the Slovak side. The project aims to contribute to the solution of a serious medical problem using advanced technologies, original expertise and new approaches developed in collaborating laboratories.
Project web page:http://confolab.sav.sk/ovsb/projekty/aktivne-projekty/jrp-2019-836-ryrinheart/

VISION - Strategies to strengthen scientific excellence and innovation capacity for early diagnosis of gastrointestinal cancer

Stratégia ako posilniť excelentnosť a inovačnú kapacitu na včastnú diagnostiku rakoviny gastrointestinálneho traktu

Duration: 1. 10. 2019 - 30. 6. 2023
Program: Horizont 2020
Project leader: RNDr. Gábelová Alena CSc.
Annotation:The main objective of VISION is to strengthen excellence and innovation capacity of the Biomedical Research Center of the Slovak Academy of Sciences (BMC SAV). Close cooperation with four European leading research institutions will enhance the credibility, competitiveness, and recognition of BMC SAV, contribute to overcome existing gaps in oncology research and reinforce the capacity for early diagnostics and innovative treatment approaches. Beyond increased scientific performance, the collaborative approach may help to identify factors contributing to an extremely high incidence of colon and pancreatic cancer in Slovakia.
Project web page:http://vision.savba.sk

TBFV - TBFVnet: surveillance and research on tick-borne flaviviruses

TBFVnet: sledovanie a výskum flavivírusov prenášaných kliešťami

Duration: 1. 7. 2020 - 31. 1. 2024
Program: Iné
Project leader: RNDr. Klempa Boris DrSc.

Role of the CA IX ectodomain in tumor growth and metastasis

Úloha ektodomény CA IX v nádorovom raste a metastázovaní

Duration: 11. 11. 2014 - 31. 12. 2022
Program: Iné
Project leader: prof. RNDr. Pastoreková Silvia DrSc.
Annotation:This project is aimed at understanding the role of the CA IX ECD in tumor growth and metastasis in vivo using mouse models. We intend to evaluate growth of tumor xenografts (following subcutaneous implantation of tumor cells) and colonization of lungs (following injection of tumor cells into the tail vein) in absence and presence of the recombinant CA IX ECD. In addition, we plan to evaluate potential therapeutic targeting of CA IX ECD through analysis of the anticancer effect of antibodies binding to different regions of the ectodomain, including M75 and VII/20. Particularly M75 is of great interest, because the N-terminal PG region, to which M75 binds, was recently found to be involved in cell adhesion and spreading, the processes contributing to metastatic dissemination. On the other hand, MAb VII/20 binds to the central CA catalytic domain and was previously shown to reduce the growth of primary tumors, but its effect on metastasis has not been examined so far. Thus, we expect that the project will allow us to dissect the role of ECD in metastasis and propose antibody-based therapeutic strategies to reduce metastatic growth.

VACCELERATE - VACCELERATE - European Corona Vaccine Trial Accelerator Platform

VACCELERATE - Európska platforma na akceleráciu klinického skúšania vakcín proti novému koronavírusu

Duration: 28. 1. 2021 - 27. 1. 2024
Program: Horizont 2020
Project leader: prof. RNDr. Pastoreková Silvia DrSc.
Annotation:The COVID-19 pandemic has underscored the need for concerted efforts towards vaccine development in Europe. The EU-funded VACCELERATE project creates a platform connecting all European vaccine development stakeholders. VACCELERATE maps clinical trial and laboratory sites across Europe and identifies the best locations for conducting Phase 2 and 3 vaccine trials. A Volunteer Registry provides access to trial participants. The network coordinates laboratory support and provides standardised assays and trial protocols. VACCELERATE identifies and shares emerging public health questions, provides answers through its own clinical trials, and lends expertise and tangible support to vaccine developers from industry and academia. With these efforts, VACCELERATE partners are creating a network ready to face emerging pandemics and enhance vaccine development capacity in Europe.
Project web page:https://vaccelerate.eu

In silico and in vitro investigation of novel nuclear retinoid X receptor (RXR) ligands as potential anti-tumour agents.

Výskum in silico a in vitro nových ligandov nukleárnych retinoidných X receptorov ako potenciálnych protinádorových látok

Duration: 1. 5. 2020 - 30. 4. 2023
Program: Iné
Project leader: Ing. Brtko Július DrSc.

National Projects

Use of microfluidic systems for risk assessment of xenobiotics

Využitie mikrofluidných systémov na hodnotenie rizika xenobiotík

Duration: 1. 1. 2021 - 31. 12. 2024
Program: VEGA
Project leader: RNDr. Šramková Monika PhD.
Annotation:Microfluidic systems coupled with different cell types offer an alternative platform for the risk assesment of different xenobiotics in order to simulate physiological conditions, improve testing, and reduce the animal use. Liver and kidney cells play a key role in the detoxification and elimination of xenobiotics and their metabolites, and represent two primary targets of the toxic effect of xenobiotics. In the present project we will use various in vitro conditions (monolayer, 3D spheroids, Transwell inserts) to evaluate the biological effect of selected xenobiotics (aflatoxin B1, ifosfamide) and gold nanoparticles, including an advanced in vitro system (IVTech), which will enable liver-kidney co-cultivation in a bioreactor to better simulate in vivo conditions. By combining biological, molecular methods, as well as imaging techniques and analytical tests, we gain new valuable knowledge about the interaction of individual tissues, the metabolism of xenobiotics and their effect on the relevant tissue.

Development of Monoclonal antibodies of Rickettsiae and their employment in diagnosis assay

Vývoj monoklonálnych protilátok Rickettsiae a ich využitie v diagnostike

Duration: 1. 1. 2019 - 31. 12. 2022
Program: VEGA
Project leader: Mgr. Quevedo Diaz Marco PhD.
Annotation:Rickettsioses are zoonotic infections caused by members of the genus Rickettsia. Rickettsial illnesses share common clinical manifestations, such as fever, malaise, exanthema, the presence or absence of an inoculation eschar, and lymphadenopathy. The reported incidence of these diseases has increased during the previous decade in Europe. In our region, Mediterranean Spotted Fever and TIBOLA(caused by Rickettsia conorii and Rickettsia slovaca respectively) continue to be the most prevalence rickettsial diseases. Due to many similar symptoms with commonly occurring infections, its clinical diagnosis is very challenging. No rapid laboratory tests are available to diagnose rickettsial diseases early in the course of illness; serological assays still remain an indispensable tool in their diagnosis. In our previous work, we were able to detect new biomarkers for diagnosis of rickettsioses. The principal aim of this study is generate specific antibodies against biomarkers (eg. Lipopolysaccharide and proteins) for de

Enhancement of endocannabinoid signaling as a promising target for the treatment of stress-related psychiatric disorders

Zvýšenie endokanabinoidnej signalizácie ako perspektívny terč pre liečbu psychických porúch podmienených stresom

Duration: 1. 1. 2022 - 31. 12. 2025
Program: VEGA
Project leader: RNDr. Hlaváčová Nataša PhD.

LEBRE - Multidrug resistance of leukemia cells - Phenotype caused by interference of multimodal molecular reasons

Viaclieková rezistencia u leukemických buniek - fenotyp spôsobený interferenciou viacerých molekulárnych príčin

Duration: 1. 7. 2020 - 30. 5. 2024
Program: APVV
Project leader: Ing. Brtko Július DrSc.

Development of a lateral flow assay for the diagnosis of zoonotic disease: Q fever.

Vývoj testu na báze laterVývoj testu na báze laterálneho toku (“lateral flow assay) na diagnostiku zoonotického ochorenia: Q horúčka

Duration: 1. 1. 2021 - 31. 12. 2024
Program: VEGA
Project leader: Mgr. Flores-Ramírez Gabriela PhD.

Nano-Neuro-Plast - Activation of the VGF/BDNF/TrkB pathway by synthetic mRNA encapsulated in polyplex nanoparticles: effects on neural excitability, neuroplasticity and animal behavior

Aktivácia VGF/BDNF/TrkB dráhy syntetickou mRNA zapúzdrenou v polyplexových nanočasticiach: účinky na nervovú excitabilitu, neuroplasticitu a správanie zvierat

Duration: 1. 7. 2021 - 30. 6. 2025
Program: APVV
Project leader: prof. PharmDr. Ježová Daniela DrSc.

POTYPLANT - Analysis of factors affecting a crop response to the potyvirus infection at the molecular and cellular level.

Analýza faktorov ovplyvňujúcich odpoveď plodiny na infekciu potyvírusmi na molekulárnej a bunkovej úrovni.

Duration: 1. 7. 2019 - 30. 6. 2023
Program: APVV
Project leader: Ing. Glasa Miroslav DrSc.
Annotation:The Potyvirus genus includes a third of all known viruses infecting crops and wild-growing plant communities. In recent years, there have been many reports of epidemic outbreak cases caused by emerging viruses or by new divergent forms of already known viruses. The aim of the project is a comprehensive analysis of the plant-virus interactions at the molecular and cellular level with focus on potyviruses causing serious damage to major crops (vegetables, potatoes, oil plants). Metagenomic analysis using next generation sequencing (NGS) will allow an unbiased view on the plant virome. In addition to full-length characterization of genomes, identification of mixed infections and previously overlooked intra-isolate diversity, we will evaluate possible evolutionary factors potentially enhancing the competitiveness of potyviruses (genome recombinations, mutations). The obtained results will be used to develop and optimize detection tools enabling specific monitoring of the virus (ory its strains or forms, respectively) in subsequent epidemiological studies (host range, cultivar sensitivity, antagonism / synergism in complex infections ...). Using potyviral infectious clones and interspecies chimeric forms, we will analyze molecular factors of host specificity by monitoring changes in pathogenesis and host spectrum. Comparison of the proteomic profiles of healthy and infected plants with various degrees of pathogen sensitivity will allow a global view of the complex biological changes induced by a potyvirus infection. Understanding the mechanism of factors influencing the evolution of the virus and its virulence is essential for the adoption of effective preventive phytosanitary measures and the efficient control of potyvirus diseases.

Analysis of the virome complexity and intra-species diversity from agricultural and wild plants in various agroecological contexts.

Analýza komplexnosti a vnútrodruhovej diverzity virómu poľnohospodárskych a divorastúcich druhov rastlín z rôznych agroekologických kontextov.

Duration: 1. 1. 2020 - 31. 12. 2023
Program: VEGA
Project leader: Ing. Glasa Miroslav DrSc.
Annotation:The recent introduction of new generation sequencing (NGS) into plant virus research has significantly altered the view on the complexity of plant viral infections while opening up new possibilities for study of plant virome. The project focuses on virome analysis using NGS, with samples coming from a variety of agroecological contexts potentially affecting the complexity of infections (perennial and annual agricultural species and wild plants). In addition to the potential identification of new viruses or highly divergent forms of known viruses, we will evaluate the genetic diversity of pathogens and the involved evolutionary mechanisms, as important factors for pathogen adaptation to the host. Genomic data will be used to analyze intraspecific molecular diversity and viral population polymorphism. Using variants-specific detection tools, the frequency and competitiveness of viral variants in mixed infections under natural and experimental conditions and their epidemiological consequences will be monitored.

Analysis of peripheral nerve regeneration after transection on the model of rat caudal nerve using tubulization and mesenchymal stem cells.

Analýza regenerácie periférneho nervu po transekcii na modeli kaudálneho nervu potkana s využitím tubulizačných techník a mezenchýmových kmeňových buniek.

Duration: 1. 1. 2021 - 31. 12. 2023
Program: VEGA
Project leader: RNDr. Blaško Juraj PhD.
Annotation:Injury of the peripheral nerve with a consequent limitation/loss of function is due to the nature of the nervous system a longterm problem in the field of medicine. Our aim in this project is to precisely quantify the extent of regeneration of a rat peripheral nerve after transection and application of tubular conduit bridging the site of injury after long term survival period (4-12 weeks). Based on our preliminary results and established method of nerve tubulization we want to focus on the identification of critical distance between two stumps of transected nerve in which regeneration still occurs. Our previous results have shown that if two nerve stumps are placed in a conduit and are oriented in a thight contact, axons of proximal stump grow into distal stump and partial re-connection occurs. In the last phase of the project we will test the potential of mesenchymal stem cells enriched conduits in the regeneration of peripheral nerve.

Anti-myeloma activity by composite realgar nanomaterials and its mechanism in vitro and in vivo

Anti-myelómová aktivita nových kompozitných nanomateriálov a ich mechanizmus účinku in vitro a in vivo

Duration: 1. 1. 2020 - 31. 12. 2022
Program: VEGA
Project leader: RNDr. Jakubíková Jana PhD.
Annotation:Myeloma resistance to therapy is a serious medical problem, and the identification of new drugs and treatments is still an ongoing task in overcoming intrinsic or treatment-induced primary resistance of tumor and/or tumor microenvironment. One promising approach is to use newly designed composite nanoparticles (NPs) prepared by nanosizing by high-energy milling and organic modification for better biocompatibility and targeted effects. The combination of new as well as conventional anti-myeloma drugs with targeted designed composite NPs efficiently link systemic chemotherapy and nanomedicine to achieve elimination of tumor mass. The proposed project develops long-term collaboration on material and oncology research to characterize cellular and molecular responses to the presence of new composite nanomaterials and to identify NPs with optimal anti-cancer activity.

CoViD - Antiviral drugs against COVID-19: Design, synthesis and biological activity testing of specific inhibitors of viral proteases of coronavirus SARS-CoV-2

Antivirálne liečivá proti COVID-19: Dizajn, syntéza a testovanie aktivity špecifických inhibítorov virálnych proteáz koronavírusu SARS-CoV-2

Duration: 1. 7. 2022 - 30. 6. 2026
Program: APVV
Project leader: Mgr. Nemčovičová Ivana PhD.
Annotation: The pandemic of the new coronavirus SARS-CoV-2, which causes serious diseases of the respiratory tract (COVID-19), poses a long-term threat to human health. The vaccination of the population with available vaccines in Slovakia is low and currently only one broad-spectrum antiviral drug - remdesivir, which is targeted to viral RNA polymerase, has been approved for the treatment of COVID-19. Our team, based on many years of experience in designing new antiviral agents (e. g. against HIV-1, HCV, Dengue, influenza A virus), has been intensively researching viral protease inhibitors since the beginning of the COVID-19 pandemic. targeted against the main protease Mpro and papain-like protease PLpro of SARS-CoV-2 virus, which are among the key pharmacological targets for antiviral therapy. The presented project builds on our previous results, which combine competencies from five experienced groups of researchers from two universities (FaF and PriF UK, UCM), together with CHÚ SAV and VÚ BMV SAV. The project strategy is based on the following integrated approach to drug research: • Computer-assisted design and optimization of specific peptidomimetic α-ketoamides that inhibit the proteolytic activity of Mpro; optimization of two series of bis-benzylidenecyclohexanones and benzamides that inhibit the proteolytic and deubiquitination activity of PLpro for the coronavirus SARS-CoV-2. • Development of synthetic routes and synthesis of peptidomimetic α-ketoamides, benzamides and bis- benzylidenecyclohexanones. • Testing for inhibition of enzymatic activity of three groups of substances on recombinantly prepared enzymes Mpro and PLpro and development of new methods for testing inhibitory activity on viral enzymes. • In vitro antiviral activity testing of three groups of substances at the level of inhibition of human cell lines infected with SARS-CoV-2 virus. • Research into the interactions of new inhibitors with biological membranes and the optimization of absorption and bioavailability.

Antiviral therapy and vaccination as tools for lowering the course of influenza and bacterial co-infection.

Antivírusová terapia a vakcinácia ako nástroj na zmiernenie priebehu chrípkovej a bakteriálnej koinfekcie.

Duration: 1. 1. 2019 - 31. 12. 2022
Program: VEGA
Project leader: RNDr. Varečková Eva DrSc.
Annotation:Infuenza A virus (IAV) infections are often complicated by bacterial coinfection ending even fatally. Antiviral therapy is applied in praxis rarely and only in case bacterial superinfection is developed, antibiotics are used. However, after necrotic pneumonia starts on, antibiotic need not be effective in recovery from severe infection. Such cases were reported during the H1N1 pandemic in 2009. It is therefore reconsidered the need of early onset of antiviral therapy to lower the risk of severe course of coinfection. The aim of our project is to know the influence of antiviral application on complex immune response induced by IAV infection, especially on protective antibody induction. The second goal is to study the influence of antiviral therapy and IAV vaccination with new vaccines on the course of coinfection. The knowledge of mechanisms started during the IAV and bacterial coinfection could answer the question of substantiation of antiviral therapy in prevention from complications related to coinfection.

GLYCO4BIO - Biochip systems for targeted glycan analysis of biomarkers for biomedical and biotechnological applications

Biočipové systémy na cielenú glykánovú analýzu biomarkerov pre biomedicínske a biotechnologické aplikácie

Duration: 1. 7. 2021 - 30. 6. 2025
Program: APVV
Project leader: Mgr. Nemčovičová Ivana PhD.
Annotation:The GLYCO4BIO project focuses on research and development of analytical systems based on microarray biochips enabling targeted and high-throughput glycoprofiling and their use in biomedicine and biotechnology. This is a strongly interdisciplinary research with a high degree of innovation, especially in the field of construction and application of original biochip devices on the microarray platform. New systems for analyzing glycan structures in various types of biological samples will be developed, verified and validated, such as a high-performance microfluidic reflectometric label-free microarray system, and an on-chip glycoprofiling platform combining microarray and MS technology. The expected benefit of the presented project is mainly in the development of innovative biochip systems for targeted glycorecognition based on modern technologies and their use in biomedicine, biotechnology, the study of biointeractions and in the analysis and screening of biomarkers. The systems will be applied, for example, in the research and detection of biomarkers of congenital disorders of glycosylation (CDG), cancer, gestational diabetes, in oncological research, as well as in the development and characterization of the therapeutic proteins. The developed biochip systems significantly outperform traditional techniques and have a high potential for their translation into clinical analysis. The expected results of the project will improve and expand the possibilities of diagnostics and therapy, and significant benefits are also expected in the expansion of knowledge in the field of biomedical research, glycoproteomics and biotechnology.

Biological effects of nitrosopersulfide and reactive sulfur species on mitochondria

Biologické účinky nitrózopersulfidu a reaktívnych foriem síry na mitochondrie

Duration: 1. 1. 2019 - 31. 12. 2022
Program: VEGA
Project leader: Mgr. Grman Marián PhD.
Annotation:Hydrogen sulfide (H2S) and nitric oxide (NO) are endogenously produced gaseous signaling molecules with similar chemical and biological properties, which affect many physiological functions. Recent results showed that reactive sulfur species (RSS), oxidation products of H2S, and nitrosopersulfide (SSNO–), product of H2S-NO interaction, also play an important role in cellular signaling. In our proposed project we aim to study the effect of RSS and SSNO– on mitochondria as crucial cell energetic centre. We will focus on their effect on chloride channels of the inner mitochondrial membrane, mitochondrial transmembrane potential, as well on their interaction with cytochrome c oxidase, which is the main target of electron transport chain during the inhibition mediated by H2S and NO. Obtained results will contribute to better understanding of RSS and SSNO– role, the new signaling molecules, in redox regulation of mitochondria and whole cells and lead to development of new drugs with potential clinical application.

Exercise in prevention & treatment of chemotherapy-related late toxicity in testicular germ cell cancer survivors: the role of skeletal muscle

Cvičenie v prevencii a liečbe neskorej toxicity chemoterapie u vyliečených onkologických pacientov: úloha kostrového svalstva

Duration: 1. 1. 2020 - 31. 12. 2023
Program: VEGA
Project leader: Mgr. Ukropec Jozef DrSc.
Annotation:Regular exercise is effective in prevention & treatment of chronic diseases. Exercise can reduce late toxicity of chemotherapy, commonly found in cancer survivors, which is yet to be translated into clinical practice. Mechanisms of exercise benefits in oncologic patients are far from being elucidated, and include increase in muscle mass, reduction of fat mass, systemic inflammation and cardiometabolic risk. Synchronization of exercise adaptive response is, to an extent, mediated by bioactive molecules released from muscle, with antiinflammatory & tumor-suppressing properties. Muscle satellite cells are a source of regeneration, muscle structural integrity & funcional capacity. Phenotypes of muscle cells, such as secretory profile, lipid & glucose metabolism, mirror clinical phenotypes of the donor. Importantly, muscle cells’ metabolism in vitro can be modulated by 8-12 week training in vivo. Epigenetic mechanisms regulating muscle & systemic metabolism in cancer survivors are not yet understood.

Cytokine profiling together with carbonic anhydrase IX immunotargeting as a promising tool in diagnostics and treatment of pancreatic cancer

Cytokínové profilovanie v spojení s imunotargetingom karbonickej anhydrázy IX ako perspektívny nástroj v diagnostike a liečbe rakoviny pankreasu

Duration: 1. 7. 2021 - 30. 6. 2025
Program: APVV
Project leader: Mgr. Švastová Eliška PhD.

Detailed analysis and elucidation of functions of Cka1 and Ksg1 protein kinases using the conditional ATP analog-sensitive mutants

Detailná analýza a objasnenie funkcie Cka1 a Ksg1 proteínkináz využitím ich kondičných na ATP analógy citlivých mutantov

Duration: 1. 1. 2022 - 31. 12. 2025
Program: VEGA
Project leader: Ing. Čipák Ľuboš PhD.

Detection of the tick borne-encephalitis virus in milk of farm animals by LAMP method as the prevention of alimentary infections

Detekcia vírusu kliešťovej encefalitídy v mlieku hospodárskych zvierat metódou Lamp ako prevencia alimentárnych infekcií

Duration: 1. 1. 2022 - 31. 12. 2024
Program: VEGA
Project leader: RNDr. Ličková Martina PhD.
Annotation:Tick-borne encephalitis (TBE) is a serious viral neurological disease caused by the tick-borne encephalitis virus (TBEV). TBEV is maintained in nature in a cycle involving the virus, ticks as vectors, and small mammals as hosts. Humans are infected through tick bites, as the main route of transmission; or by alimentary route after the consumption of raw milk of infected goats and sheep. Slovakia has the highest number of TBE foodborne diseases in Europe. The presented project aims to develop a quick test for TBEV detection in milk, intended for use directly at the sampling point. The test will be based on the LAMP method, which we adapt specifically for TBEV detection in milk. We will examine samples of sheep's and goat's milk from Slovak farms as well as milk samples of sheep and goats infected in the laboratory (cooperation with FLI in Germany). Milk samples will be also evaluated by the RT-qPCR. The project results will help to improve the safety of the consumption of unpasteurized dairy products.

Diagnostic of oncological diseases using aptasensors: development and validation

Diagnostika onkologických ochorení pomocou aptasenzorov: vývoj a validácia

Duration: 1. 1. 2021 - 31. 12. 2024
Program: VEGA
Project leader: Mgr. Bábelová Andrea PhD.
Annotation:DNA aptamers, also referred to as DNA antibodies, are short single-stranded sections of DNA that form spatial structures that allow high-affinity to interact with receptors and other biomolecules. The project aims to develop and validate a new diagnostic method that utilizes the unique affinity properties of DNA aptamers for the early detection of cancer. In terms of project aims, we will analyze the molecular mechanisms of interactions between DNA aptamers and specific markers found on the surface of the tumor cells. We plan to use a sensitive method of quartz microbalances (QCM), which allows real-time monitoring of interactions. For practical use, we plan to prepare conjugates of selected aptamers and gold nanoparticles depending on their physicochemical parameters and their interaction with neoplastic cells. We have the ambition to identify factors currently limiting the wider use of aptamers and aptamer-modified nanoparticles in clinical practice and contribute to their elimination.

Diversity of vector-borne pathogenic and non-pathogenic microorganisms and potential therapy of zoonotic diseases caused by them

Diverzita vektormi prenášaných patogénnych a nepatogénnych mikroorganizmov a potenciálna terapia nimi spôsobených zoonotických ochorení

Duration: 1. 1. 2021 - 31. 12. 2024
Program: VEGA
Project leader: Mgr. Špitalská Eva PhD.
Annotation:Tick-borne zoonotic infections are among the most spread vector-borne diseases, they are caused by different microorganisms, such as tick-borne encephalitis virus, Rickettsia spp., Coxiella burnetii, Ehrlichia spp., Borrelia spp., Francisella tularensis, Babesia spp. Changes in the incidence of ticks cause changes in the incidence of vector-borne pathogens and the development of new outbreaks making them constantly at the center of attention. Tick microbiome includes not only pathogens but also various symbionts, interacting with each other. In the era of increasing antibiotic resistance, there is a need for alternative methods of treatment, which could be photodynamic therapy at an early stage of infection. The proposed project is focused on the study of pathogens and symbionts present in their vector, the host, to explain their mutual influence, genetic diversity, incidence, prevalence and to test the possibility of using photodynamic therapy to treat tick-borne infections in vitro.

OBEZITA - Long-term strategic research of prevention, intervention and mechanisms of obesity and its comorbidities

Dlhodobý strategický výskum prevencie, intervencie a mechanizmov obezity a jej komorbidít

Duration: 1. 9. 2019 - 28. 2. 2023
Program: Štrukturálne fondy EÚ Výskum a inovácie
Project leader: prof. RNDr. Pastoreková Silvia DrSc.

Dominant mutations in Wolfram syndrome: different mechanism to the recessive ones?

Dominantné mutácie u Wolframovho syndrómu: potenciálne rozdielny mechanizmus účinku v porovnaní s recesívnymi mutáciami

Duration: 1. 1. 2019 - 31. 12. 2022
Program: VEGA
Project leader: RNDr. Cagalinec Michal PhD.
Annotation:Wolfram syndrome is a rare hereditary disorder caused by mutations in the Wolframin1 gene. Product of this gene, the Wolframin1 (WFS1) is located in the membrane of endoplasmic reticulum (ER). WFS1 is highly expressed in pancreas, brain and heart. Function of WFS1 involves regulation of ER stress and modulation in calcium homeostasis. Moreover it affects mitochondrial dynamics and ATP production in neurons. Although Wolfram syndrome is traditionally considered as recessive disorder, in our patients, we have identified two novel mutations of WFS1 resembling dominant behaviour. Therefore in this project we plan to evaluate, whether these novel mutations of are dominant and whether dominant and recessive mutations in the WFS1 gene act via different signalling pathways in the matter of ER stress, calcium metabolism and their impact to mitochondrial dynamics. These parameters will be tested in a model of human neuronal and cardiac cell lines to reveal unique mechanisms of WFS1 function in the brain and heart.

Ecology of West Nile virus in globally changing environment

Ekológia West Nile vírusu v prostredí ovplyvnenom globálnou zmenou

Duration: 1. 1. 2021 - 31. 12. 2024
Program: VEGA
Project leader: RNDr. Čabanová Viktória PhD.

Exosomes secreted by cancer cells of digestive organs, their characterization and modification by the CRISPR/Cas9 system for the aim of use in therapy

Exozómy vylučované bunkami nádorov tráviaceho traktu, ich charakterizácia a modifikácia CRISPR/Cas9 systémom s cieľom ich využitia na terapiu

Duration: 1. 1. 2021 - 31. 12. 2024
Program: VEGA
Project leader: RNDr. Kozovská Zuzana PhD.
Annotation:The Extracellular exosome-type vesicles (30-150 nm) secreted by tumor cells reflect the nature of the tumor. They are able to regulate the stemnes of tumor cells, create a premetastatic niche in the target organs of future metastasis, transmit chemoresistance and their genetic content can be altered by modifying of the cells from which they are secreted. Using the CRISPR/Cas9 gene editing technique, we will change in cancer cell lines key genes associated with exosome biogenesis, targeting of exosomes to the site of the premetastatic niche (lungs and liver), the activation of the epitelial-mesenchymal transition and with the stemnes required for metastasis of the primary tumor. From these edited cell lines we will isolate exosomes which we will apply to chemoresistant tumor cells to test the rate of their proliferation, migration. In vivo we will test the ability of exosomes from an edited and control cancer cell line to prevent the formation of metastases.

CA(9)NNIBAL - Cell-in-cell phenomena as microevolutionary processes in cancer progression: a role for hypoxia-induced carbonic anhydrase IX

Fenomény “bunka v bunke” ako mikroevolučné procesy v nádorovej progresii: úloha hypoxiou-indukovanej karbonickej anhydrázy IX

Duration: 1. 7. 2020 - 30. 6. 2024
Program: APVV
Project leader: prof. RNDr. Pastoreková Silvia DrSc.
Annotation:Cell-in-cell phenomena refer to situations, in which tumor cells (“winner cells”) engulf one or more viable cells (“loser cells”) to gain nutrients in periods of starvation. Such cell-in-cell structures have been observed in human tumors for decades, but the underlying mechanisms and relevance to cancer progression has remained largely unexplored. Emerging view on molecular and functional aspects of cell-in-cell phenomena suggests their involvement in microevolutionary processes that occur in highly heterogeneous tumor tissues and lead to selection of aggressive tumor cells. Despite increasing interest in cell-in-cell phenomena, their understanding still remains fragmentary. In this project, we aim to elucidate the contribution of hypoxia and acidosis in tumor microenvironment to two cell-in-cell processes, namely cell cannibalism and entosis, with particular focus on carbonic anhydrase IX (CA IX), which plays a key role in pH regulation as an adaptive response of tumor cells to hypoxia and oncogenic metabolism. To achieve this aim, we intend to employ state-of-the-art approaches of molecular and cell biology and experimental oncology, and to use unique CA IX expertise and specific reagents developed by our team since our discovery of CA IX. According to our working hypothesis, CA IX participates in induction of cell-in-cell structures and is associated with “winner” phenotype enabling tumor cells to sustain starvation, survive microenvironmental stresses and gain aggressive properties. We also hypothesize that CA IX does so via participation in metabolic rewiring, morphological plasticity, intercellular signalling and protection of tumor cells from hypoxia and acidosis. Finally, we propose that hypoxia and acidosis are microenvironmental stimuli that trigger formation of cell-in-cell structures and thereby accelerate microevolution in tumor tissue. These hypotheses are supported by preliminary results and implicit evidences from our published and unpublished data.
Project web page:-

Functional analysis and production of bioactive subsatnces in insects and ticks

Funkčná analýza a produkcia bioaktívnych látok hmyzu a kliešťov

Duration: 1. 7. 2019 - 30. 6. 2023
Program: APVV
Project leader: RNDr. Koči Juraj PhD.
Annotation:In this project we will use molecular, bioinformatics, biochemical a physiological techniques for description of expression patterns and functional characterization of membrane guanylate cyclases which serve as receptors for large neuropeptides of insects and ticks - eclosion hormone (EH) and ion transport peptides (ITP and ITPL). Various experiments using physiological, molecular and genetic approaches indicate that these neuropeptides are required for regulation of normal development, homeostasis, metabolism and reproduction, but mechanisms of their action are not known. Since peptides of EH and ITP/ITPL family elicit cGMP production in target cells, we assume that their receptors are guanylate cyclases. We plan to use model insects Bombyx mori and Drosophila melanogaster which are most suitable for physiological experiments and genetic manipulations. The knowledge obtained from these studies will be utilized for RNAi knock-down of these receptors to suppress development and reproduction of ticks (Ixodes ricinus and I. scapularis). These ticks are in Europe the most important vectors of numerous pathogens causing serious diseases in humans and domestic animals. In addition, we will examine expression and function of receptors for biogenic amines (dopamine and GABA) which are very important for modulation of physiological processes during blood feeding of ticks.

Functional analysis of regulation of DEAH/RHA helicases

Funkčná analýza regulácie DEAH/RHA helikáz

Duration: 1. 1. 2019 - 31. 12. 2022
Program: VEGA
Project leader: Ing. Čipáková Ingrid PhD.
Annotation:RNA helicases from the DEAH/RHA family are involved in most of the processes of RNA metabolism. It has been shown that function of these helicases might be regulated by protein partners containing a glycine-rich domain, known as G-patch domain. Although it has been shown these proteins stimulate DEAH/RHA helicase enzymatic activities, their precise roles remain unclear. In the proposed project, we will analyse and characterize in detail the interactome and function of known as well as our recently identified new G-patch proteins of fission yeast S. pombe for their role in regulation of DEAH/RHA helicases. Analysis of protein-protein and protein-nucleic acid interactions of G-patch proteins and DEAH/RHA helicases will allow us to characterize the precise structural features of helicase activation. Comprehension of the mechanisms of regulation of DEAH/RHA helicases by G-patch proteins will help us to better understand the fine regulation of essential processes of RNA metabolism.

Genetics of rare forms of diabetes with focus on functional characterization of new variants

Genetika vzácnych foriem diabetu s dôrazom na funkčnú charakterizáciu nových variantov

Duration: 1. 1. 2021 - 31. 12. 2024
Program: VEGA
Project leader: RNDr. Škopková Martina PhD.
Annotation:Diabetes mellitus significantly affects both quality of life and life expectancy and it's etiology determines correct treatment. In HNF1A-MODY, insulin can be replaced with tablets and, after confirmation of GCK-MODY, no treatment is needed at all. Still, however, a large proportion of people with MODY does not have a proper diagnosis. In part of them, a DNA variant of unknown significance has been identified. This project is dedicated to the determination of pathogenicity of new variants in genes for the transcription factor HNF1A and for the GCK glucokinase using functional studies. Impact on DNA binding, transactivation and intracellular localization will be assessed in case of variants in the HNF1A gene. Variants affecting splicing in any gene will be analysed using mini-gene essays. The project will contribute to the knowledge about the structure of these genes, with results being directly applied to clinical practice, as it will allow to adapt therapy in patients with a confirmed pathogenic variant.

GlycoPro - Glycoprofiling of proteins present in serum and exosomes for early prostate cancer diagnostics

Glykoprofilácia proteínov prítomných v sére a v exozómoch pre včasnú diagnostiku rakoviny prostaty

Duration: 1. 12. 2019 - 30. 12. 2022
Program: Iné projekty
Project leader: RNDr. Gábelová Alena CSc.
Annotation:In this project we would like to identify novel glycan-based prostate cancer (PCa) biomarkers based on specific glycoprofiling of selected proteins either present in serum or in exosomes. We will integrate various assay protocols for such glycoprofiling using lectin-based ELISA, magnetic ELISA, antibody-lectin microarrays, electrochemistry, Surface Plasmon Resonance (SPR) and LFA (Lateral Flow Assays, pregnancy-like tests). The innovation of the project proposal can be summarized as follows: • Specific glycoprofiling of zinc -glycoprotein (ZAG) and prostatic acid phosphatase (PAP) present in the serum as potential PCa biomarkers; • Use of exosomes as a rich source of five glycoproteins to be glycoprofiled by lectins; • Application of innovative assay strategies with various assay formats; glycoproteins/exosomes will be affinity enriched by magnetic beads and the whole complex without any glycoprotein/exosome released will be incubated with lectin modified interface; • Use of LFA for glycoprofiling of proteins, which has not been used in the analysis of real samples.

Herpesviral immunomodulators as novel candidates in therapy of cancer and inflammatory diseases

Herpesvírusové imunomodulátory ako noví kandidáti na liečbu rakoviny a zápalov

Duration: 1. 1. 2021 - 31. 12. 2024
Program: VEGA
Project leader: RNDr. Lopušná Katarína PhD.

LEONORA - Verification of clinically relevant biomarkers for the stratification of CRC patients by molecular and bioinformatic methods.

Hľadanie klinicky relevantných biomarkerov pre stratifikáciu CRC pacientov použitím molekulárnych a bioinformatických metód.

Duration: 1. 1. 2022 - 31. 12. 2025
Program: VEGA
Project leader: Ing. Poturnajová Martina PhD.
Annotation:The Slovak Republic has the second highest incidence and mortality from colorectal cancer (CRC) in the world. 50% of patients develop metastases and 40% of stage II-III patients relapse within 5 years after surgical treatment. Research therefore focuses on identifying high-risk patients using new prognostic biomarkers. In the project we will analyze the expression of newly discovered long non-coding RNAs (lncRNAs), their correlation with disease prognosis, chemoresistance and metastasis and verify the possibility of their use as a prognostic biomarker of the disease. The results could enable to define the risk groups of CRC patients with a worse prognosis or indicate the treatment decision between a more radical vs. gentle therapy for an individual patient. Linking applied research with the needs of the clinical oncology using the latest biostatistical and bioinformatics methods allows us to approach the personalized treatment of CRC patients.

Impact of selected metal nanoparticles on steroidogenesis: comparison of in vitro cell models

Hodnotenie účinkov vybraných kovových nanočastíc na steroidogenézu: porovnanie in vitro bunkových modelov

Duration: 1. 1. 2020 - 31. 12. 2022
Program: VEGA
Project leader: Mgr. Scsuková Soňa CSc.
Annotation:Nanoproducts are becoming widely used in all aspects of life. Different types of NPs are often used in everyday products, such as cosmetics and foods. In medicine, nanoparticles (NPs) can be used as nanoscopic drug carriers and for nanoimaging technologies. Unique physicochemical properties of NPs (size, shape, polarity) may allow for their passage through biological barriers and thus, to have easier access to the organs and tissues in the body. NPs have been reported to induce reproductive toxicity, but the molecular mechanisms remain unclear. Reproductive physiology involves a series of complex physiological processes, including synthesis of steroid hormones that are sensitive to chemical contaminants. The present project will be focused on evaluation of impact of selected metal NPs with different physicochemical properties on steroidogenesis by considering gonadal and adrenal cells as vitro model systems. The obtained results provide new knowledge to guide safe and sustainable development of new NPs.

TESTOX - Identification and validation of biomarkers and underlying molecular pathways of late toxicity of curative treatment in testicular germ cell tumors

Identifikácia a validácia biomarkerov a zodpovedných molekulárnych dráh neskorej toxicity kuratívnej liečby u germinatívnych nádorov testis

Duration: 1. 7. 2020 - 30. 6. 2024
Program: APVV
Project leader: prof. MUDr. Ukropcová Barbara PhD.
Annotation:Testicular germ cell tumors (GCTs) are a unique malignancy with a long-term cure rate > 95%. The implementation of multi-modality treatment with cisplatin-based chemotherapy, radiotherapy and surgery have rendered GCTs as model for cancer cure. Growing population of GCT survivors can suffer from late toxicity of treatment, ultimately leading to lower quality of life, increasing long-term morbidity and early mortality. Among the known late toxic sequelae are secondary malignancies, cardiovascular toxicity, neurotoxicity, nephrotoxicity, pulmonary toxicity, hypogonadism, infertility, cognitive dysfunction, sexual function impairment and decline in quality of life. Proposed project aims to further develop ongoing programme of late toxicity research in National Cancer Institute in Slovakia. The project will focus on longitudinal assessment of distinct types of late toxicities and identify biomarkers and underlying molecular mechanisms. Two interventional randomized studies will be conducted to assess the effects of endurance and strength training. This project is the first state-of-the-art approach to implement comprehensive joined clinical and translational research with an attempt to identify and further analyse late toxicity of anti-cancer treatment also integrating the programme for prevention. The project is also considered to be a pilot comprehensive programme for survivorship initiatives and research applicable among other cancer types.

Identification of biomarkers of resistance to cisplatin-based chemotherapy in urogenital cancer

Identifikácia biomarkerov rezistencie na chemoterapiu cisplatinou pri nádoroch urogenitálneho traktu

Duration: 1. 1. 2019 - 31. 12. 2022
Program: VEGA
Project leader: Mgr. Chovanec Miroslav PhD.
Annotation:Testicular germ cell tumors (TGCT) affect young and bladder tumors (TCC) older men. Both cancers are curable with cisplatin (CDDP), but after first-line therapy, resistance to this drug may develop. Disease relapse can be associated with DNA repair and we assume that patients who relapse may have a more effective repair of CDDP-induced DNA damage due to different expression of DNA repair factors at both the mRNA and protein levels, as well as due to their post transcriptional and -translational regulation. Using TGCT and TCC cell lines displaying different CDDP sensitivity levels, we will identify mRNAs and miRNAs associated with resistance to this drug. We will also reveal the role of alternative mRNA splicing and phosphorylation in regulation of selected DNA repair factors. Finally, we will determine the extent of endogenous DNA damage in TCC and by correlating the obtained results with clinical data we will identify biomarkers of CDDP resistance. Selected biomarkers will be validated in clinical material.

Identification of etiology in sporadic forms of hereditary hearing loss by whole exome sequencing

Identifikácia etiológie sporadických foriem dedičnej poruchy sluchu pomocou sekvenovania novej generácie

Duration: 1. 1. 2021 - 31. 12. 2024
Program: VEGA
Project leader: RNDr. Gašperíková Daniela DrSc.

Identification of chemoresistant cell populations with metastatic potential in colorectal carcinoma

Identifikácia chemorezistenntých bunkových populácií s metastatickým potenciálom u kolorektálneho karcinómu

Duration: 1. 1. 2019 - 31. 12. 2022
Program: VEGA
Project leader: RNDr. Matúšková Miroslava PhD.
Annotation:Colorectal cancer (CRC) belongs to leading causes of cancer-related mortality worldwide as well in Slovak Republic. Metastases occur in more than half of the patients suffering from this disease, and they represent the key obstacle to the effective treatment of CRC. The majority of patients can not be cured. It is obvious that population of tumour cells which is not eliminated by chemotherapy consists of subpopulations which are capable to induce metastases. Based on published data as well as on our research it is evident that functional link between chemoresistance and metastatic process does exist. We aim to define the set of markers typical for chemoresistant cells with metastatic potential on the model of CRC and contribute to identification of characteristics typical for metastasis-initiating cells. The implementation of project will help to solve actual clinically-relevant issues associated with patients suffering from metastatic disease.

Identification of new treatment options in refractory testicular germ cell tumors

Identifikácia nových možností liečby u refraktérnych testikulárnych nádorov zárodočných buniek

Duration: 1. 7. 2021 - 30. 6. 2025
Program: APVV
Project leader: Ing. Schmidtová Silvia PhD.

Identification of Potential Therapeutic Targets Associated with Cisplatin Resistance in Yolk Sac Tumors

Identifikácia potenciálnych terapeutických cieľov asociovaných s rezistenciou voči cisplatine u nádorov zo žĺtkového vaku

Duration: 1. 1. 2021 - 31. 12. 2024
Program: VEGA
Project leader: Ing. Schmidtová Silvia PhD.

Identification of the protein markers activated in the process of induction of the ischemic tolerance

Identifikácia proteinových markerov aktivovaných v procese navodenia ischemickej tolerancie

Duration: 1. 1. 2020 - 31. 12. 2022
Program: VEGA
Project leader: RNDr. Mucha Rastislav PhD.

Inhibition of Carbonic Anhydrase IX (CA IX) Circumventing Cisplatin Resistance in Refractory Testicular Germ Cell Tumours

Inhibícia karbonickej anhydrázy IX (CA IX) ako nástroj prekonania rezistencie voči cisplatine u refraktérnych testikulárnych nádorov zo zárodočných buniek

Duration: 1. 1. 2021 - 31. 12. 2023
Program: VEGA
Project leader: Ing. Schmidtová Silvia PhD.

RENASTHERA - Novel renal antisense therapy platform for CKD

Inovatívna antisense terapeutická platforma pre CKD - chronické ochorenie obličiek

Duration: 1. 8. 2021 - 30. 6. 2025
Program: APVV
Project leader: Mgr. Bábelová Andrea PhD.
Annotation:Chronic kidney disease (CKD) with its progressive nature towards end-stage renal disease (ESRD) is a lethal and rapidly progressing severe health complication associated with significantly decreased quality of life and high mortality rates. Strikingly, despite the progress made in early-diagnostics of CKD, state-of-the-art therapeutics do not significantly decrease the risk of renal and cardiovascular morbidity and mortality rates in CKD patients which remain devastatingly high. This fact highlights an urgent need not only for novel therapeutics but also for the implementation of progressive experimental and clinical tools into translational drug discovery. In this context, the proposed RENASTHERA project offers a novel therapeutic solution to stop progressive renal function loss. This solution is based on a patented method of nucleic acid inhibition. Periostin, a 90 kDa secreted protein was identified as a key player in CKD development, inhibition of which effectively prevented CKD progression. The design, synthesis, and functional validation of an RNA inhibitor specifically designed for periostin RNA is thus the clearly defined scope of the proposed RENASTHERA project.

LISPER - Integrative strategy in the development of personalized medicine of selected malignant cancer diseases and its effect on the quality of life

Integratívna stratégia v rozvoji personalizovanej medicíny vybraných zhubných nádorových ochorení a jej vplyv na kvalitu života

Duration: 1. 9. 2019 - 30. 6. 2023
Program: Štrukturálne fondy EÚ Výskum a inovácie
Project leader: Mgr. Chovanec Miroslav PhD.

COXHOST - Host cell interaction with Coxiella burnetii: identification and utilization of novel therapeutic and diagnostic targets

Interakcia hostiteľských buniek s Coxiella burnetii: identifikácia a využitie nových terapeutických a diagnostických cieľov

Duration: 1. 7. 2020 - 30. 6. 2024
Program: APVV
Project leader: Ing. Škultéty Ľudovít DrSc.
Annotation:Coxiella burnetii is an intracellular bacterial pathogen causing human infections of clinical and public health relevance. As many other bacterial pathogens, Coxiella uses specialized secretion systems to manipulate eukaryotic host cells by injection of effectors (bacterial virulence proteins and small molecules). However, current knowledge about how these pathogens establish infection is limited. The central research commitment of this project is the characterization of the functions of effector proteins from Coxiella burnetii. The project’s specific objectives include: 1) the description of the host cell signaling pathways targeted by effectors (proteins and small molecules) of Coxiella burnetii; 2) the characterization of the molecular and cellular mode of action of the effectors, and 3) a putative correlation between the mode of action of the effectors to their sequence variability and expression amongst different strains. The anticipated results may lead to the discovery of novel therapeutic approaches-drug targets- and could help in the design of vaccines and novel diagnostics. In particular, the host signaling pathways altered by one (or more) effector(s) will be promising candidates as novel therapeutic targets. Furthermore, the knowledge that will be gained could also lead to the identification of inhibitors targeting the pathogen’s effectors directly and help to design specifically drugs that can block the secretion system of the pathogen.

Interaction of bioactive compounds and non-thermal plasma

Interakcie bioaktívnych látok a nízkoteplotnej plazmy

Duration: 1. 1. 2021 - 31. 12. 2024
Program: VEGA
Project leader: Mgr. Horváthová Eva PhD.

CATCA - Interactions of calcium transport systems in carcinogenesis

Interakcie vápnikových transportných systémov v karcinogenéze

Duration: 1. 7. 2021 - 30. 6. 2025
Program: APVV
Project leader: prof. Ing. Križanová Oľga DrSc.

Isolation, identification and characterization of transforming growth factor-beta 1 binding molecule(s) in tick salivary gland extracts.

Izolácia, identifikácia a charakterizácia transformujúci rastový faktor-beta 1 viažúcej molekuly v extraktoch slinných žliaz kliešťov.

Duration: 1. 1. 2019 - 31. 12. 2022
Program: VEGA
Project leader: Mgr. Bartíková Pavlína PhD.
Annotation:The transforming growth factor-beta 1 (TGF-b1) and its signaling pathway play a pivotal role in coordinating almost every aspect of normal tissue repair and homeostasis. The perturbation of TGF-b1 signaling is linked to autoimmunity, inflammation and cancer. The discovery of pro-oncogenic properties of TGF-b1 stimulated development of TGF-b1 signaling inhibitors as therapeutic strategy for combating cancer. Tick saliva contains an extraordinary array of biologically active molecules disarming host hemostatic, inflammatory and immune reactions; some of them with promising therapeutic potential. Considering this possibility and according to our discovery of tick salivary gland compounds ability to bind TGF-b1, we focus on isolation, identification and characterization of TGF-b1 binding molecule(s) from different tick species. Given the pleiotropic effects of TGF-b1, ticks and their molecular armaments may provide valuable tools and insights into aberrant wound repair and disorders.

MiReCheT - Is HIF-1a a master regulator of DNA repiar capacity and chemotherapy response in testicular germ cell tumors?

Je HIF-1a hlavný regulátor DNA reparačnej kapacity a odpovede na chemoterapiu v nádoroch semenníkov z germinatívnych buniek?

Duration: 1. 7. 2020 - 30. 6. 2023
Program: APVV
Project leader: RNDr. Jurkovičová Dana PhD.
Annotation:Testicular germ cell tumors (TGCT) are highly curable malignity with cisplatin (CDDP) first line chemotherapy, gaining excellent response rates even in advanced metastatic stages. However, approximately 20-30% of patients do not respond to this treatment or relapse. These patients are predominantly young men and have a very poor prognosis. Early detection of CDDP resistance in these patients may be essential for the immediate initiation of more effective treatments that eliminate exposure of the patient to unnecessary CDDP cytotoxicity without therapeutic effect. Binding of CDDP to DNA and DNA damage are the major toxic and therapeutic effects of this treatment. CDDP generated DNA adducts can lead the cell to apoptosis and eliminate it, or be repaired by various DNA repair mechanisms, particularly homologous recombination (HR) and nucleotide excision repair (NER), which, by increased repair capacity, can critically contribute to CDDP resistance. In this project we will focus on the identification and characterization of molecular mechanisms responsible for modulating the efficiency of DNA repair by HR and NER and their role in chemoresistance, namely the regulatory role of hypoxia by hypoxia inducible factor (HIF, typical for solid tumors) and epigenetic regulation of DNA repair genes by miRNA and promoter methylation. Such modulation of repair capacity may explain the different response of TGCT to CDDP. We will attempt to answer the question whether HIF-1a can be the master regulator of this answer. Our intention is to identify early biomarkers of CDDP responses that would enable stratification of the TGCT patients prior to initiation of therapy or predict patients' sensitivity to other therapeutics, e.g. PARPi. The project outputs have the potential for transfer to clinical practice.

Is hypoxia a master modulator of DNA repair capacity and mitochondrial dynamics in chemotherapy response in urogenital malignancies?

Je hypoxia kľúčovým modulátorom DNA reparačnej kapacity a metabolizmu mitochondrií v odpovedi testikulárneho karcinómu na chemoterapiu?

Duration: 1. 1. 2021 - 31. 12. 2024
Program: VEGA
Project leader: RNDr. Jurkovičová Dana PhD.
Annotation:Testicular germ cell tumors (TGCT) are cisplatin (CDDP) well treatable malignancy, with excellent response even in advanced metastatic stages. 20-30% of patients do not respond, relaps, and have a poor prognosis due to CDDP resistance. Several mechanisms are responsible for tumor cell resistance, leading the tumor cell to survive and avoid apoptosis. In the proposed project we will focus on: 1) DNA repair mechanisms contributing to the resistance increased capacity of DNA damage repair and 2) metabolism of mitochondria (dynamics, mitophagy) whose changes are critical for the cell response to induction of cell death. In the resistance of TGCT and other solid tumors, hypoxia and associated epigenetic modulation (by miRNA and methylation) are believed to be the key regulators. On TGCT cell lines we will focus on DNA damage and repair and selected mitochondrial proteins, and we will try to identify signaling pathways where HIF-1α and miRNA are the major regulators of these changes. Our aim is to identify and validate early molecular markers informing about CDDP resistance of TGCT patients before treatment initiation.

Carbonic anhydrase IX: one of the key components of exosomes secreted from cancer cells

Karbonická anhydráza IX: jeden z kľúčových komponentov exozómov sekretovaných z nádorových buniek

Duration: 1. 1. 2020 - 31. 12. 2023
Program: VEGA
Project leader: RNDr. Zaťovičová Miriam CSc.
Annotation:Knowledge of the cellular processes that govern exosome biology is essential to shed light on the physiological and pathological functions of these vesicles, as well as for clinical applications. Current evidence suggests that exosomes participate in many key tumor-promoting processes. The subject of the proposed project is the exosome-located, tumor-associated protein carbonic anhydrase IX (CA IX), and implication of this enzyme’s extracellular form in many processes, such as its role in the tumor microenvironment, cancer metastasis, and in cancer immunity. We will use not only the latest in vitro cell biology methods in the project, including real-time cell parameter measurements but also in vivo experiments. Results of this project are expected to extend our knowledge on function of CA IX located in exosomes as an important cancer cell messenger, as well as a potential clinical biomarker.

ACE2MAS - Cardiometabolic effects of Mas receptor stimulation by modulation of the renin-angiotensin system - the key role of angiotensin-converting enzyme 2.

Kardiometabolické účinky stimulácie Mas receptorov modulovaním renín-angiotenzínového systému - klúčová úloha angiotenzín-konvertujúceho enzýmu 2.

Duration: 1. 7. 2021 - 30. 6. 2025
Program: APVV
Project leader: Ing. Zorad Štefan CSc.
Annotation:The renin-angiotensin system (RAS) is a hormonal cascade whose chronic activation contributes to the development of cardiovascular pathologies caused mainly by remodeling of the heart and blood vessels. It is becoming apparent that the benefit of RAS inhibitors includes, in addition to Ang II inhibition, stimulation of the alternative arm of RAS mediated by the ACE2/Ang1-7/Mas receptor, which has vasodilatory, antiproliferative, anti-inflammatory and metabolic effects. The aim of the present project will be to compare the effect of ACE inhibition, AT1 blockade, stimulation of ACE2 (diminazene) and Mas receptor (cyclic Ang1-7, alamandine) in a model of old, obese, diabetic hypertensive Zucker rats with a focus on the potential benefit of Ang1-7/Ang1-5 on glucose utilization, insulin signal transduction, reduction of the inflammatory response and function of the cardiovascular system. Given the potentially key role of RAS and especially ACE2 in the development of acute respiratory distress syndrome (ARDS) and the severe course of COVID-19, the aim of the present project will be to detect changes in membrane and serum ACE2 and expression of other key molecules for viral infection (ADAM17, TMPRSS2, furin and B0AT1 transporter) using various pharmacological interventions. The dependence of the putative alterations on the activity of the Mas receptor will be monitored by its specific antagonist A779. In vitro, following treatment of human alveolar cells and adipocyte cultures with RAS and diminazene inhibitors, the changes in the ability to bind SARS-CoV-2 virus will be assessed using a pseudoviral methodology. The obtained results might contribute to the elucidation of the role of ACE2 and Mas receptor in the pathogenesis of obesity and diabetes. The project might also contribute to the clarification of the choice of an effective RAS inhibitor in the elderly with a combination of hypertension, obesity and diabetes.

MAHYCAMA - Clinical evaluation of prognostic and predictive value of tissue and serum Carbonic Anhydrase IX in breast cancer

Klinická evaluácia prognostickej a prediktívnej hodnoty tkanivovej a sérovej karbonickej anhydrázy IX v karcinómoch prsníka

Duration: 1. 11. 2019 - 31. 12. 2022
Program: Iné projekty
Project leader: RNDr. Režuchová Ingeborg PhD.
Annotation:Intratumoral hypoxia has clinically serious consequences, since cell adaptation to hypoxia increases resistance to anticancer drugs, radiotherapy, and leads to the expansion of cells with a more aggressive phenotype and to increasing tumor metastatic potential. Carbonic Anhydrase IX (CAIX) is a transmembrane protein whose expression is induced by HIF-1α transcription factor during hypoxia. CAIX is currently considered as an independent marker of poor prognosis, overall survival, and marker for assessing the risk of distant metastasis. The project aim is to define predictive and prognostic value of tissue-associated CAIX (tCAIX) and soluble CAIX (sCAIX) in breast cancer (CaMa) patients. We will analyze the presence of tCA IX in biopsy specimens obtained pre-operative during early diagnosis, in tumor tissue and/or sentinel node obtained during surgery. We will supplement this examination by monitoring sCAIX levels in patients' plasma before and during treatment, and follow-up care. sCAIX will be quantitated using a new ELISA.

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Kontrolné body a vírusové immunomodulatory v nádorovej terapii

Duration: 1. 9. 2022 - 31. 8. 2025
Program: SASPRO
Project leader: RNDr. Lopušná Katarína PhD.

The yeast Saccharomyces cerevisiae as a model to study the repair of clinically relevant DNA damage

Kvasinka Saccharomyces cerevisiae ako model pre štúdium mechanizmov opravy klinicky významných poškodení DNA

Duration: 1. 1. 2020 - 31. 12. 2023
Program: VEGA
Project leader: RNDr. Goffa Eduard PhD.
Annotation:This project aims to further characterize two clinically relevant DNA repair pathways in S. cerevisiae: non-homologous end-joining (NHEJ) and interstrand crosslink (ICL) repair. We will study the impact of SUMOylation of the ligation complex components Dnl4/Lif1/Nej1, mainly the Nej1 protein, on NHEJ. As the substitution K181R significantly decreases Nej1 SUMOylation in vitro, we will inquire whether it happens also in vivo and whether K181R impacts NHEJ efficiency. This effect could be caused by changes in ligation complex interactions with other NHEJ proteins, as well as changes in oligomerization of Nej1 itself. Next, we will focus on ICL repair specific for the S-phase of the cell cycle. We found out that the nuclease Rad1/Rad10 is partially involved in ICL repair in the S-phase even without the presence of the accessory protein Rad14, the major component of the nucleotide excision repair (NER). Our aim is to clarify the role of Rad1 in NER-independent ICL repair specific for the S-phase.

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Laktát, metabolický signál a zdroj energie pre alternatívne termogénne mechanizmy

Duration: 1. 2. 2022 - 31. 1. 2025
Program: SASPRO
Project leader: Mgr. Baláž Miroslav PhD.

CAScADE - Markers overlapping chemoresistance and metastatic potential in colorectal cancer - alhedyde dehydrogenase and its clinical relevance

Markery prekrývajúce chemorezistenciu a metastázovanie kolorektálneho karcinómu - úloha aldehyddehydrogenázy a jej klinická relevancia

Duration: 1. 11. 2019 - 31. 12. 2022
Program: Iné projekty
Project leader: RNDr. Matúšková Miroslava PhD.
Annotation:Metastases occur in more than half of the patients suffering from colorectal cancer (CRC). Their prognosis is unfavourable. Acquired chemoresistance is significant obstacle in treatment of patients with metastases. There is an increasing number of evidence that there is a functional overlap between chemoresistance and metastatic dissemination. The mechanisms of this phenomenon are not fully understood in CRC. We demonstrated significantly increased activity of aldehyde dehydrogenases (ALDH), particularly the 1A3 isoform on chemoresistant-spontaneously metastatic cell line. Transient molecular silencing of ALDH1A3 led to partial response to chemotherapy. We aim to verify a hypothesis that ALDH1A3 or other ALDH1 isoforms are common marker for chemoresistance and invasive phenotype in CRC, and knockout of ALDH1, or inhibition of associated signalling pathways, decreases the aggressive phenotype. The clinical relevance we confirm on organoids and patient-derived xenografts as well as by retrospective analysis of clinical material archived in biobank of National Cancer Institute.

The mechanism of action of virus-specific cross-reactive antibodies on dual infection with influenza virus and bacteria

Mechanizmus účinku vírus-špecifických krížovo-reaktívnych protilátok na duálnu infekciu vírusom chrípky a baktériami

Duration: 1. 1. 2021 - 31. 12. 2024
Program: VEGA
Project leader: RNDr. Tomčíková Karolína PhD.

Mechanisms of skeletal muscle adaptation to regular exercise in patients with chronic metabolic and inflammatory disease

Mechanizmy adaptácie kostrového svalu pacientov s chronickým metabolickým a zápalovým ochorením na pravidelné cvičenie

Duration: 1. 1. 2019 - 31. 12. 2022
Program: VEGA
Project leader: RNDr. Novotová Marta CSc.
Annotation:Low physical fitness is associated with impaired muscle functional parameters and high risk of chronic metabolic disease. In patients with idiopathic inflammatory myopathy, skeletal muscle function deteriorates also because of systemic inflammatory process, but it often persists even after suppression of inflammation. Regular exercise positively affects energy metabolism and muscle functional state in healthy individuals as well as in patients with metabolic disease or myopathy. Aim of this project is to identify structural, functional and molecular determinants of beneficial effects of exercise on mitochondrial respiration, metabolic substrate preference, myocyte ultrastructure and contractile function. Skeletal muscle biopsy & differentiated muscle cells obtained from metabolically well-characterized patients before/after the exercise intervention will be used. This knowledge is a key to our efforts to tackle the basic pathophysiological determinants of idiopathic inflammatory myopathy.

Mechanisms of glutamate metabolism as a tool of ischemic tolerance

Mechanizmy metabolizácie glutamátu ako nástroj ischemickej tolerancie

Duration: 1. 1. 2021 - 31. 12. 2023
Program: VEGA
Project leader: RNDr. Bonová Petra PhD.
Annotation:The role of glutamate in the CNS changes diametrically under the pathological conditions associated with ischemia. Its neurotoxic effect (excitotoxicity) is one of the basic parameters determining the resulting range of infarction of the brain. Induction of the ischemic tolerance is manifested by low levels of extracellular glutamate in the brain, which is probably related to significant neuroprotection. However, the mechanisms of glutamate metabolism activated in the tolerant phenotype remain unclear.

MitoHF - Mitochondrial disease in heart failure

Mitochondriálne ochorenia a zlyhanie srdca

Duration: 1. 7. 2022 - 30. 6. 2026
Program: APVV
Project leader: RNDr. Zahradníková, ml. Alexandra PhD.
Annotation:Several mutations in mitochondrial genes of respiratory chain proteins are associated with heart failure (HF). The extent of their contribution to the development of HF at the level of cardiomyocytes (CM) is unknown. Recent findings indicate that various HF etiologies share similar remodeling of CM, especially of their membrane system and calcium signaling. The project is aimed to validate the in vitro model of HF development in a genetic disorder with reduced function of mitochondrial respiratory chain and to verify at the cellular level prevention of HF development by metabolic therapy with nutritional supplements. We will use the HL-1 CM cell line with allotopic expression of a mutant form of the MT-ND5 gene for subunit 5 of respiratory complex I (mG13513A), associated with human hypertrophic cardiomyopathy, to determine the impact of diseased mitochondria on cytoarchitecture and contractile function of cardiac myocytes. By methods of electron and confocal microscopy, cell electrophysiology, oxygraphy, and molecular biology, we will monitor expression and localization of dyadic proteins and changes in mitochondrial structure, localization, and oxidative capacity. Since genetic cardiomyopathy cannot yet be addressed by gene therapy, we will investigate the benefits of metabolic therapy for the compensation of invalidated mitochondrial function. We will compare in HL-1 CM the effect of the hereditary mitochondrial insufficiency with that of HF development imposed by overstimulation. We expect that nutritional supplementation of mitochondrial function will improve CM performance and suppress the development of HF. Results will be published in leading experimental cardiology and physiology journals and publicize them on the projec t website and in the media. Three PhD students and several M.S. students will participate in the project.
Project web page:http://confolab.sav.sk/ovsb/projekty/aktivne-projekty/apvv-21-0443/

LEGOMICS - Modern "omics" approaches as effective tools for identification and characterization of leguminous viral pathogens

Moderné "omics" postupy ako efektívne nástroje pre identifikáciu a charakterizáciu vírusových patogénov strukovín

Duration: 1. 7. 2021 - 30. 6. 2025
Program: APVV
Project leader: Ing. Glasa Miroslav DrSc.
Annotation:Legumes (the Fabaceae family) represent a nutritionally and economically important crop, important for human and livestock nutrition. However, the quality and quantity of legume production can be adversely affected by a complex of viral pathogens. Available knowledge on the presence, epidemiology and diversity of phytopathogenic legume viruses in field conditions, collections of long-term genetic resources and wild-type Fabaceae species in Slovakia are insufficient. The aim of the presented project is unbiased and accurate identification of the viruses present on legumes and subsequent genomic characterization of pathogens in our territory using modern sequencing approaches. The data obtained will be used to develop effective detection methods and targeted molecularepidemiological studies taking into account the regional diversity of pathogens, including seed-borne infectious agents. The susceptibility of selected legume genotypes to viral infection is evaluated by experimental inoculation with characterized virus isolates. The mutual interaction of selected genotypes of legumes and the investigated biotic pathogen will be analyzed by modern methods of cellomic research including next generation sequencing (genomics, transcriptomics) and the proteome will be studied by classical immunochemical methods in combination with modern analytical-chemical methods based on mass spectrometry (LC-MS / MS, nanoLC-ESI-Q-TOF). By combining these currently most progressive methods in plant virology, we obtain accurate and detailed data necessary for the most comprehensive evaluation of the pathogen / plant relationship. The methodological platform used, using modern and efficient genomic, transcriptomic, proteomic and in silico procedures, will provide important knowledge for the diagnosis and characterization of viral diseases and also knowledge for improving the quality of legume cultivation in Slovakia.

MolBioSem - Molecular biomarkers of relapse in seminoma clinical stage I patients

Molekulárne biomarkery relapsu pri seminómoch klinického štádia I

Duration: 1. 10. 2019 - 21. 12. 2022
Program: Iné projekty
Project leader: Mgr. Chovanec Miroslav PhD.
Annotation:Clinical stage I seminoma (S-CS I) patients have a very good prognosis, reaching 98% survival. However, a small proportion of these patients relapse and the prognosis of these patients is significantly worse. There are currently no reliable biomarkers that stratify S-CS I patients, although primary tumor size ≥ 4 cm and rete testis invasion (RTI) are considered to be negative prognostic factors. The present project aims to identify molecular biomarkers that timely and accurately stratify S-CS I patients according to the risk of relapse. We intend to find molecular biomarkers of RTI, whose expression significantly associates with the risk of relapse in S-CS I patients. The factors of poor prognosis in S-CS I will further be sought within DNA repair processes, where the levels of DNA repair proteins will be correlated with the level of their regulation through epigenetic mechanisms and hypoxia. We will also examine proliferative activity as well as lymphocyte infiltrate in S-CS I patients. To achieve these goals, a comprehensive interdisciplinary approach using a wide range of methods and biological material will be used.

IZOTIOVIVO - Molecular mechanisms of trialkyl-/triaryltin isothiocyanates' and carboxylates' antitumour properties - novel ligands of nuclear retinoid X receptors in rat mammary gland carcinomas and human tumour cell lines

Molekulárne mechanizmy protinádorových vlastností trialkyl- /triarylcíničitých izotiokyanátov a karboxylátov, nových ligandov jadrových retinoidných X receptorov v karcinómoch mliečnej žľazy potkana a v ľudských nádorových bunkách prsníka

Duration: 1. 7. 2021 - 30. 6. 2025
Program: APVV
Project leader: Mgr. Macejová Dana PhD.
Annotation:Organometallic compounds, on account of their structural diversity, are applied in human oncology in the treatment of cancer. Triorganotin derivatives showed significant cytotoxic properties. At the cellular level, they induce massive cell death in various types of cell cultures even at low concentrations and are able to activate the processes of apoptotic pathways, in which several molecular mechanisms play a role. A significant breakthrough in knowledge was our recent experimental confirmation of the ability of molecules of triorganotin compounds to bind to nuclear retinoid X receptors, and thus function as potent agonists. The aim of the present project is to investigate the in vivo effects of tributyl/triphenyltin isothiocyanates in the process of chemical carcinogenesis of the mammary gland of female rats, which is based on our current results of in vitro experiments. Simultaneously, the research of antitumour properties of triorganotin compounds activating RXR-RAR heterodimers comprising novel RXR agonists based on triorganotin carboxylates, is envisaged. In vitro analyses of molecular mechanisms leading to inhibition of tumour cell growth or induction of apoptosis in the presence/absence of natural ligands of RAR receptors on human breast tumour cell lines: MCF-7 (non-invasive, ER positive), T47D (ER positive), MDA-MB-231 (invasive, triple negative) and MDA-MB-436 (invasive, ER negative, PR negative), will be accomplished. We also plan to achieve new data on the possible endocrine disruption of triorganotin compounds on the murine TM3 cell line and the human COV434 cell line representing the reproductive system. We assume that the presented project will gain new and original knowledge about the mechanism of the action of the studied substances through their binding and activation of nuclear receptors, their transactivation as well as crosslink with other signalling pathways that may contribute to the development of novel treatment options for breast cancer.

Molecular regulatory mechanisms and therapeutic potential of retinoid X receptor activation by triorganotin compounds in relation to breast cancer treatment

Molekulárne regulačné mechanizmy a terapeutický potenciál aktivácie retinoidných X receptorov triorganocíničitými zlúčeninami vo vzťahu k liečbe nádorových ochorení prsníka

Duration: 1. 1. 2021 - 31. 12. 2023
Program: VEGA
Project leader: Mgr. Macejová Dana PhD.
Annotation:Tributyl/triphenyl tin (TBT/TPT) compounds are organic tin derivatives characterized by covalent bonds between the three carbon atoms and the tin atom. TBT/TPT as environmental pollutants can cause DNA damage. Exposure to triorganotins in mammals results in immunosuppressive, metabolic, reproductive and developmental disorders through binding to retinoid X receptors. Triorganotin derivatives have shown cytotoxic properties against tumour cell lines. The aim of the present project is to study the role of these compounds in the processes of transactivation of retinoic acid-induced transcription factor regulatory signals, the mechanism of action of these compounds through their potential endocrine disruption, and their possible induction of apoptosis and inhibition of invasive tumour cell proliferation and migration. The results obtained will be reflected in the "design" of in vivo experiments using an experimental model of mammary carcinogenesis to evaluate the benefit/risk ratio of therapy.

WOLPACMUT - Mutations associated with Wolfram syndrome: alternative signaling pathways for calcium and mitochondrial physiology

Mutácie asociované s Wolframovým syndrómom: rozdielne signálne dráhy v zmysle metabolizmu vápnika a funkcie mitochondrií

Duration: 1. 7. 2022 - 30. 6. 2026
Program: APVV
Project leader: RNDr. Cagalinec Michal PhD.
Annotation:Wolfram syndrome (WS), characterized by diabetes insipidus, diabetes mellitus, optical atrophy and deafness, is caused by mutations in WFS1 gene. Protein WFS1 is highly expressed in the brain and pancreas where its mutations are in line with the symptoms. Moreover, a high expression has been observed in the heart; however, in the vast majority of WS cases the cardiac symptoms have not been reported. WFS1 is localized in the membrane of endoplasmic reticulum (ER) and strongly impacts calcium metabolism, mitochondrial function and ER stress. However, the principal question about WFS1 function still remains open – why the pancreatic β-cells and neurons are affected severely in WS, and why are the alterations in myocytes jut minor, when WFS1 is highly expressed in them? Possible explanation could be a yet unresolved compensatory mechanism present in myocytes and/or a different signalling pathway(s) when compared to neurons/ β-cells. Therefore, the first hypothesis is: Do the calcium metabolism and mitochondrial dynamics differ in cardiac myocytes when compared to neurons and pancreatic β-cells in case of WFS1 malfunction? The majority of WS cases represent recessive mutations; however, several dominant mutations have been identified as well. Therefore the second hypothesis is: Do the calcium metabolism and mitochondrial dynamics differ in cells expressing pathogenic dominant vs. recessive Wfs1 mutations? Moreover, complete novelty of the project represents characterization of the heterozygous WFS1 deletion variant recently identified in the first Slovak WS patient at the applicant’s institute. Use of up-to-date approaches including CRISPR/Cas9 gene editing, optogenetic techniques, confocal microscopy and the know-how of the proposed research team will help to resolve the WFS1 function which will serve for development of early diagnostics and effective treatment not only for WS, but also for diabetes mellitus and highly prevalent cardiovascular diseases.
Project web page:http://confolab.sav.sk/ovsb/projekty/aktivne-projekty/apvv-21-0473/

iMMunoedit - Cancer immunoediting in multiple myeloma: immune checkpoints and clinical significance

Nádorové imunoeditovanie v mnohopočetnom myelóme: imunitné kontrolné body a klinický význam

Duration: 1. 8. 2021 - 30. 6. 2025
Program: APVV
Project leader: RNDr. Jakubíková Jana PhD.
Annotation:The understanding of cancer immunoediting, immune defense mechanisms against cancer, has been challenging in multiple myeloma (MM). A hallmark of the myeloma microenvironment is profound immune dysregulation and loss of immune surveillance. The overall objective is to characterize immunoediting in MM using cellular and molecular approaches. We will focus on understanding the complex innate and adaptive immune systems during the development of MM: from premalignant conditions MGUS and smoldering MM to symptomatic MM. We will define diverse immune checkpoint mechanisms and their biological sequelae on tumor promoting/suppressing immune subsets within the tumor microenvironment together with MM cells as well as blockage role of novel immune checkpoint inhibitors in ex vivo. Moreover, we will define the impact of anti-MM therapies on modulation of MM immunoediting in a homogeneously treated cohort of MM patients, allowing us to evaluate the impact of suppressed immune system on emergence of resistant tumor clones; and vice versa. MM immunoediting of primary patient samples together with immune checkpoint mechanisms, including regulatory co-stimulation/tumor antigen/checkpoint molecules and signaling pathways, will be evaluated using mass cytometry. These studies will identify mechanisms and biologic sequelae of immunoediting in MM, and provide for rational design of targeted and immune therapy in MM.

SCIATR - The neuroprotection of synergic effect of the AT1 receptor blockade and AT2 receptor stimulation after traumatic spinal cord injury

Neuroprotektívny vplyv synergického pôsobenia blokovania AT1 a stimulácie AT2 receptorov po traumatickom poranení miechy

Duration: 1. 7. 2019 - 30. 6. 2023
Program: APVV
Project leader: RNDr. Pavel Jaroslav PhD.
Annotation:Spinal cord injury (SCI) usually causes permanent and often devastating neurologic deficits and disability. Despite a neuroprotective effects in experimental studies, most of the promising therapies fail in clinical studies and up to present time, efficient and trustworthy clinical treatment available for SCI patient is still missing. An essential prerequisite for finding effective therapy is a thorough knowledge of mechanisms that are ongoing in the spinal cord under physiological as well as pathological conditions. Angiotensin II, as main effective hormone of the renin-angiotensin system (RAS) exerts its effect through stimulation of two major receptor types: AT1 and AT2. The majority of physiological as well as pathological processes associated with Angiotensin II are mediated through AT1 receptor stimulation. AT1 receptor blockers are, among other things, a strong neuroprotective substances, what is supported by the results of many scientific experiments. Angiotensin II receptor type 2 (AT2) is absent or very sparsely expressed in most tissues under physiological conditions, however, it is strongly up-regulated after tissue damage. Recently published studies indicated a neuroprotective effects of AT2 receptor stimulation under various pathological conditions. Despite the progress, the precise mechanisms of AT2R action are still not very well known, and its role is controversial. The proposed project contributes to clarify the role of AT2 receptor in neuroprotection and it assumes a substantially more neuroprotective effect of synergic AT2 receptor stimulation and AT1 receptor blockade after experimental trauma-induced spinal cord injury.

CoViDRUGS - New Antiviral Drugs: Design, Synthesis and Activity Evaluation of Specific Inhibitors of Viral Proteases of Coronavirus SARS-CoV-2

Nové antivirálne liečivá: Dizajn, syntéza a testovanie aktivity nových špecifických inhibítorov virálnych proteáz koronavírusu SARS-CoV-2

Duration: 16. 9. 2020 - 31. 12. 2022
Program: APVV
Project leader: Mgr. Nemčovičová Ivana PhD.
Annotation:The pandemic of the new coronavirus SARS-CoV-2, which causes serious diseases of the respiratory tract (COVID-19), poses a long-term threat to the health of the population. Although intensive research into vaccines and antiviral drugs is underway worldwide, only one broad-spectrum antiviral drug, the prodrug remdesivir, has been approved for the treatment of COVID-19. Therefore, a key task worldwide is to find new specific antivirals against SARS-CoV-2. Our team, based on previous experience in designing new antiviral agents (e.g. against HIV- 1, HCV, Dengue, influenza A virus), began immediately after the COVID-19 outbreak intensive research into inhibitors effective against viral proteases - main protease Mpro and papain-like protease PLpro of SARS-CoV-2 virus, which are among the key targets for inhibition of viral replication. The previous results are followed in this project. Our team combines competencies of five experienced groups from universities (UCM, FaF and PriF UK) and Academy od Sciences (CHÚ SAS and VÚ CBMV SAS). The project strategy is based on an integrated approach. In the proposed project we focus on: • Computer-assisted design and optimization of new specific peptidomimetic α-ketoamides that inhibit the proteolytic activity of Mpro and of a series of bis-benzylidene cyclohexanones that inhibit the deubiquitination activity of PLpro of the coronavirus SARS-CoV-2. • Development of synthetic routes and synthesis of peptidomimetic α-ketoamides and bis- benzylidenecyclohexanones. • Testing of inhibition of enzymatic activity of both groups of substances on recombinantly prepared enzymes Mpro and PLpro and development of new methods for testing for inhibitory activity on viral enzymes. • Testing the antiviral activity of both groups of substances at the level of inhibition of human cell lines infected with SARS-CoV-2 virus. • Research into the interactions of new inhibitors with biological membranes and optimization of absorption in the respiratory tract

Newly syntethized thymol derivatives: relationship between structure and biological activity in colorectal in vitro model.

Novosyntetizované deriváty tymolu: vzťah medzi štruktúrou a biologickou aktivitou na in vitro modeli čreva.

Duration: 1. 1. 2020 - 31. 12. 2023
Program: VEGA
Project leader: RNDr. Kozics Katarína PhD.
Annotation:Beneficial effects of thymol (TY), a naturally occurring phenol monoterpene of essential oil from thyme, on human health are well known for many years. It is widely used in medical practices, cosmetics, agriculture and as a natural remedy. However due to its low solubility in aqueous media its use e.g. in food industry is limited. The proposed project is focused on the synthesis of hydrophilic derivatives of TY while the antioxidative and antiproliferative properties as well as the effective cellular uptake will remain intact. Using comprehensive approaches from biochemistry, biology, and molecular biology will enable us to assess the biological effects of these derivatives depending on their molecular structure. The project will contribute to gain an insight into the molecular mechanisms of action of hydrophilic TY derivatives. The biological activity will be studied using 2D and 3D colorectal cell models cultured in vitro.

New insight into the phase variation phenomenon of Coxiella burnetii

Nový pohľad na fenomén fázovej premeny u Coxiella burnetii

Duration: 1. 1. 2019 - 31. 12. 2022
Program: VEGA
Project leader: Ing. Škultéty Ľudovít DrSc.
Annotation:Coxiella burnetii, a highly pleomorphic intracellular Gram-negative bacterium, causes multiple outbreaks of Q fever worldwide, each year. Human Q fever, generally resulting from inhalation of infectious aerosols produced by domestic animals, exhibits a wide spectrum of clinical manifestations. The bacterium undergoes a host-dependent phase transition. However, redistribution of lipopolysaccharide (LPS) molecules have been observed due to an increasing prevalence of those cells in l population that express LPS with truncated O-chains, the nature of this phenomenon has not been yet sufficiently elucidated. Thus, we believe that isolation of the cell population propagated under various nutritional conditions as well as the clones of spontaneous LPS mutants, followed by identification and ccharacterization of differentially presented proteins and changes in LPS structure, will provide an important insight into the molecular mechanisms underlying this transition and reveal novel diagnostic antigens or therapeutics.

Unraveling the role of genetic predispositions in the context of breast cancer tumor microenvironment

Objasnenie úlohy genetických predispozícií v kontexte nádorového mikroprostredia karcinómu prsníka

Duration: 1. 1. 2020 - 31. 12. 2023
Program: VEGA
Project leader: Mgr. Cihová Marína PhD.

Unraveling the mechanisms linking obesity and cancer progression: the interplay between adipocytes and cancer cells

Odhalenie mechanizmov spájajúcich obezitu s nádorovou progresiou: interakcia medzi adipocytmi a nádorovými bunkami

Duration: 1. 1. 2020 - 31. 12. 2023
Program: VEGA
Project leader: RNDr. Takáčová Martina PhD.
Annotation:Obesity is a major public health concern because it increases the risk of several diseases, including cancer. Crosstalk between obesity and cancer seems to be very complex, potentially acting directly on cells, or indirectly via changes in the tumor microenvironment. One of the proposed mechanisms underlying the risk association is the adipocyte-mediated secretion of adipokines. Adipokines, acting locally or systemically, play important roles in the growth, local invasion, metastatic spread, and resistance to treatment of different types of cancer. Therefore, a great interest exists to understand the molecular mechanisms by which adipocytes contribute to carcinogenesis. This project will examine on the impact of adipokines on the biological characteristics of cancer cells exposed to hypoxia and/or acidosis, focusing on carbonic anhydrase IX that is a well-known marker of tumor hypoxia, expression of which significantly correlates with poor prognosis and resistance to therapy.

MMSR - Disclosure of the molecular mechanism of spontaneous tumor regression followed by the development of novel prognostic tool

Odhalenie molekulárneho mechanizmu spontánnej regresie nádorov s nasledným vývojom nového prognostického nástroja

Duration: 1. 7. 2019 - 30. 6. 2023
Program: APVV
Project leader: Mgr. Minichová Lenka PhD.
Annotation:Spontaneous regression of tumor is a phenomenon that was reported in virtually all types of human malignancies. Recently, our team has observed this anti-tumor activity after high dose therapy and autologous stem cell transplantation in patients with Hodgkin’s disease, multiple myeloma, and some other malignancies. It seems to be associated with aplastic anemia like syndrome and ongoing pancytopenia induced by autoimmunity directed against hematopoietic stem cells. To understand the interconnected processes occurring in vivo we need to detect, identify, and structurally characterize clinically essential molecules involved in the depletion of tumor cells or tumors as a whole. We will therefore perform a systematic comparative proteomic analyses of control and treated (with polyclonal Abs of patients in regression/specific mAbs or other discovered target molecules) tumor cells. The obtained results will allow to reveal essential molecules associated with induction of tumor regression and recognize prognostic markers useful for monitoring the disease development. These finding will not only lead to a deeper understanding of this phenomenon at the molecular level, but in the link with novel information obtained from protein-protein interaction studies based on advanced proteomic analyses will contribute to future targeted therapy of certain malignancies and to design a valuable diagnostic tool for monitoring the progress of the disease.

OPENMED - Open scientific community for modern interdisciplinary research in medicine

Otvorená vedecká komunita pre moderný interdisciplinárny výskum v medicíne

Duration: 1. 11. 2019 - 30. 6. 2023
Program: Štrukturálne fondy EÚ Výskum a inovácie
Project leader: RNDr. Gálik Ján CSc.
Annotation:The project proposal aims to create a complementary scientific-research biomedical structure and in the consortium - which consists of UPJŠ Košice, UVLF Košice, NbÚ BMC SAV, TUKE Košice, Advanced Diagnostic Focus p. r. about. (ADF) and Hospital Košice-Šaca a.s. 1. private hospital (Šaca Hospital) - to solve scientific biomedical problems divided into three activities: nanomedicine (biomedical engineering), regenerative medicine and personalized diagnostics. Instrumentation and expertise will be provided in the project through central specialized technology platforms: Optical bio-imaging, Tissue and cell laboratory, Experimental vivarium, Histological Laboratory, Laboratory of Biochemical and Molecular Analyzes and Laboratory of Additive Biomedical processes. The project will be solved in the laboratories of UVP MEDIPARK UPJŠ, CIB UPJŠ, laboratories built during the implementation of OP R&D in UPJŠ, NbÚ BMC SAS, UVLF and with the help of capacities and expertise of commercial partners in the project. The main output indicators are generally definable at two levels: i) launch of some technology platforms and ii) realization of scientific objectives, which we generally characterize as: a) research and development (R&D) of drug delivery systems, b) R&D of adult stem cells and development of modern methods of cell treatment, c) R&D of imaging procedures and teranostic nanoparticles for biomaterials, cells and tissues, d) R&D of modern 3D printed tissue replacements and cell carriers, e) R&D of new approaches in CNS and nervous tissue regeneration, f) R&D in areas of new diagnostic procedures for precise personalized diagnostics, g) R&D in the field of diagnostics of selected viral infections and h) R&D in the field of interconnection of medical imaging systems with a database knowledge system. The main goal - the application of research results in practice and in the commercial area is ensured by the cooperation of the applicant with commercial partners who provide the clinical and basic research part of the project.

A pilot study of the selective effects of a new generation of RNA interfering agents at the cellular level

Pilotná štúdia selektívneho pôsobenia novej generácie RNA interferenčných agens na bunkovej úrovni

Duration: 1. 1. 2020 - 31. 12. 2023
Program: VEGA
Project leader: Mgr. Šelc Michal PhD.
Annotation:The proposed project is based on the in-depth understanding of the current scientific and clinical knowledge of chronic myelogenous leukemia (CML) and the therapeutic regimens based on RNA interference. The project aims at a highly ambitious goal: to explore the selective effect of a novel platform of RNA interfering agents at the cellular level in order to evaluate its therapeutic potential for action without side effects that would result from undesired molecular interactions. From this perspective, the project focuses primarily on an extensive study of cellular internalization, inhibition of the formation of fusion BCR-ABL1 protein, selectivity of RNA interfering agents towards the target mRNA and its effect in cells resistant to currently applied therapeutics.

KINSPL - Post-translational regulation of pre-mRNA splicing factors

Posttranslačná regulácia faktorov zostrihu pre-mRNA

Duration: 1. 7. 2021 - 30. 6. 2024
Program: APVV
Project leader: Ing. Čipák Ľuboš PhD.

BISRISK - Potential risk of use of analogs of endocrine disruptor Bisphenol A: determination of cellular and molecular effects in a spectrum of in vitro gonadal cell cultures

Potenciálne riziko používania analógov endokrinného disruptoru Bisfenolu A: hodnotenie účinkov na bunkovej a molekulovej úrovni v spektre in vitro gonadálnych bunkových kultúr

Duration: 1. 7. 2019 - 30. 12. 2022
Program: APVV
Project leader: Mgr. Bujňáková Mlynarčíková Alžbeta PhD.

PRO4CML - Preclinical validation of an innovative antisense platform for CML

Predklinická validácia inovatívnej antisense platformy pre CML

Duration: 1. 7. 2020 - 30. 6. 2024
Program: APVV
Project leader: Mgr. Bábelová Andrea PhD.
Annotation:Currently, chronic myelogenous leukemia (CML) is widely treated with tyrosine kinase inhibitors (TKIs) that effectively inhibit proleukemic activity of the causal BCR-ABL oncoprotein. However, long-term clinical experience with TKIs shows that these drugs are not sufficiently selective and specific for CML cells and BCR-ABL, respectively. This phenomenon often results in clinically significant adverse events responsible for deterioration of TKI treatment outcomes and decreased quality of life. Moreover, limited therapeutic effect of TKIs towards CML stem cells cause that patients with CML are in most of the cases long-term treated, but not completely cured. The development of alternative treatment strategies that exclusively target only CML cells and provide a possibility of permanent cure, is therefore of paramount need. The proposed PRO4CML project is directly related to the successful APVV-15-0215 project (total IF of the scientific output > 80), which was aimed at testing of an innovative antisense concept for BCR-ABL silencing in patients with CML. Thanks to its original design and mechanism of action, this progressive concept showed unprecedented potential in terms of selective recognition of target nucleic acid and, most importantly, exceptional translational potential in terms of selective biological action exclusively in tumor cells. Since the conceptual solution is fully universal, it is expected to overcome the major obstacles that have so far hindered antisense therapeutics from entry to clinical practice. The PRO4CML project is thus a natural continuation of the scientific work of the project consortium and represents the cornerstone for robust in vivo preclinical validation. If successful, the proposed concept is also expected to provide an original therapeutic platform not only in CML but also in other diseases with known molecular basis, where a particular protein plays a causal role in disease pathophysiology.

BRIDGE - Bridge between the mental state and neuroendocrine function of mother and her child: the mechanisms involved

Premostenie psychiky a neuroendokrinných funkcií matky a jej dieťaťa: zúčastnené mechanizmy

Duration: 1. 7. 2019 - 30. 6. 2023
Program: APVV
Project leader: prof. PharmDr. Ježová Daniela DrSc.

Reprogramming of host cell metabolism induced by lymphocytic choriomeningitis virus infection

Preprogramovanie metabolizmu hostiteľskej bunky vyvolané vírusom lymfocytovej choriomeningitídy

Duration: 1. 1. 2019 - 31. 12. 2022
Program: VEGA
Project leader: Ing. Tomášková Jana PhD.
Annotation:Viral replication depends on the energy and biosynthetic precursors supplied by the host cell metabolic network. Viruses actively reprogram host cell metabolism to establish optimal environment for genome replication, virion production, and enhanced survival of infected cells. While there are common metabolic changes induced by most viruses studied, there are also unique virus-specific metabolic modifications. Therefore, it is crucial to perform a detailed study for each virus species to understand these specific metabolic changes. The main goal of the proposed project is to reveal how lymphocytic choriomeningitis virus (LCMV) modulates host cell metabolic processes to ensure successful infection. We will focus mainly on LCMV-induced changes in central carbon metabolism. Understanding how LCMV reprograms cellular metabolism will provide new information on the biology and pathogenesis of LCMV and other arenaviruses. Moreover, it may open new strategies to combat pathogenic arenaviruses through targeted inhibition of specific cellular metabolic pathways.

Génové manipulác - Preparation of new antibiotics and antitumor agents by manipulations of secondary metabolite genes and synthetic biology methods

Príprava nových antibiotík a protinádorových látok manipuláciami génov sekundárnych metabolitov a metódami syntetickej biológie

Duration: 1. 7. 2020 - 30. 6. 2024
Program: APVV
Project leader: RNDr. Jakubíková Jana PhD.

Dbl2 - Dbl2 protein as a novel regulator of genome stability and dynamics in fission yeast

Proteín Dbl2 ako nový regulátor stability a dynamiky genómu v kvasinkách Schizosaccharomyces pombe

Duration: 1. 7. 2019 - 31. 12. 2022
Program: APVV
Project leader: Ing. Čipák Ľuboš PhD.

Plant systems for transient expression of peptidic substances as a tool for preparation of anti-viral vaccines

Rastlinné systémy pre tranzientnú expresiu látok peptidovej povahy za účelom prípravy vakcín proti vírusovým ochoreniam

Duration: 1. 1. 2022 - 31. 12. 2024
Program: VEGA
Project leader: RNDr. Šubr Zdeno CSc.
Annotation:Vectors based on Plum pox virus (PPV) genome will be applied for the expression of antigens originating from medically important viruses (Influenza A virus, SARS-CoV-2) in a model plant species Nicotiana benthamiana and also in other herbaceous and woody PPV hosts. In the case of free polypeptide expression, we will optimize its production and subsequent extraction and purification from plant tissues. Regarding the production of virus-like particles (VLPs) expressing the antigenic molecule on its surface, we will focus on the determination of cloning capacity of the relevant vector (maximum insert size), or the impact of insert localization and sequence on the infectivity of resulting construct, as well as its purification from plant material.

Tubular conduits for axonal regeneration after peripheral nerve injury.

Regenerácia axónov poškodeného periférneho nervu v tubulárnych vodičoch

Duration: 1. 1. 2020 - 31. 12. 2022
Program: VEGA
Project leader: MVDr. Vanický Ivo CSc.

Regulation of pyruvate dehydrogenase kinase 1 activity in the control of glycolytic metabolism in hypoxic tumors

Regulácia aktivity pyruvát dehydrogenázy kinázy 1 pri ovplyvňovaní glykolytického metabolizmu v hypoxických nádoroch

Duration: 1. 1. 2019 - 31. 12. 2022
Program: VEGA
Project leader: PharmDr. Goliaš Tereza PhD.
Annotation:Hypoxic tumor microenvironment actively shifts metabolism from oxidative to glycolytic in cancer cells. This adaptation is believed to conserve oxygen and metabolic substrates necessary for sustained proliferation, and it also makes tumor cells more aggressive. Apart from upregulating glycolysis, mitochondrial function is also actively downregulated in hypoxia, through the induction of pyruvate dehydrogenase kinase 1 (PDHK1) that inhibits pyruvate dehydrogenase, a gate-keeper enzyme between mitochondrial tricarboxylic-acid cycle and cytosolic glycolysis. We have found that hypoxia not only induces PDHK1 expression but it also acutely regulates its enzymatic activity, although the molecular mechanism remains largely unknown. Since hypoxia elevates cAMP levels, which in turn activate protein kinase A (PKA), and in silico analysis identified putative PKA-phosphorylation sites on PDHK1, we therefore hypothesize that this type of post-translational modification could potentially regulate PDHK1 activity in hypoxia.

Regulation of preadipocyte differentiation and adipocyte metabolism by oxidative stress in rat and human tissue culture.

Regulácia diferenciácie preadipocytov a metabolizmu adipocytov oxidačným stresom v potkanej a ľudskej bunkovej kultúre.

Duration: 1. 1. 2020 - 31. 12. 2022
Program: VEGA
Project leader: Ing. Zorad Štefan CSc.

Regulation of epithelial-mesenchymal transition by microRNA and promoter methylation in invasive breast cancer

Regulácia epiteliálno-mezenchymálneho prechodu prostredníctvom mikroRNA a metylácie promótorov v invazívnych nádoroch prsníka

Duration: 1. 1. 2019 - 31. 12. 2022
Program: VEGA
Project leader: RNDr. Fridrichová Ivana CSc.
Annotation:Hematogenous or lymphogenous spread of breast carcinoma (BC) leads to metastatic disease in 7-35 % of patients; therefore, the new prognostic markers for invasion and metastasis are needful. We evaluated expression of miRNAs and EMT genes in relation to CDH1/E-cadherin changes in samples from 31 patients with invasive ductal BC; namely, in tumor centrum and invasive front, lymph node metastasis (LNM), and CD45-depleted blood (CD45-DB). We did not verify CDH1 regulations found in experiments. However, we did detected extremely high ZEB1 expression in LNMs from patients with distant metastasis. Regarding the ZEB1 functions, this finding indicates enhancement of metastatic potential of lymphogenously disseminated BC cells. We found downregulated miR-205-5p in CD45-DB with CTC that could contribute to insusceptibility and survival of hematogenously distributed BC cells by increased expression of targets as ZEB1. miR-205-5p and ZEB1 gene are promising candidates as markers for metastatic potential in ductal BCs.

Regulation of M1/M2 polarization: the effect on neuron survival, axonal growth and functional recovery after spinal cord trauma

Regulácia M1/M2 polarizácie: vplyv na prežitie neurónov, rast axónov a funkčnú obnovu po poranení miechy

Duration: 1. 1. 2021 - 31. 12. 2023
Program: VEGA
Project leader: RNDr. Lukáčová Nadežda DrSc.
Annotation:Proposed project is aimed to 1) study molecular changes that regulate transformation of neuroinflammatory M1 microglia to A1 astrocytes in acute/subacute phase after Th9 compression, 2) characterize time-dependent regulation of M1/M2 polarization, a key factor in activation of pro-regenerative molecules, 3) investigate selected markers for identification of pro-inflammatory cytokines, infiltration of M1/M2 macrophages, activation of resident cells (astrocytes and microglia) and infiltration of lymphocytes in the spinal cord, blood serum and in the small intestine after Th9 compression and antibiotics, probiotics and anti-inflammatory treatment. To determine which of mechanisms regulates M1/M2 polarization, and which signaling pathways (P13K/Akt; PLC-γ/CAMK a PLC-γ/PKC) are responsible for neuroplasticity and cells survival. To investigate neuroregenerative and neuroprotective effect of treatment on tissue integrity, axonal sprouting, synaptic activity and functional recovery in chronic stage of SCI.

NEUROGEN - Neurotransmitter-mediated regulation of postnatal neurogenesis in the rat olfactory system under physiological and pathological conditions

Regulácia postnatálnej neurogenézy v čuchovom systéme potkana prostredníctvom neurotransmiterov za fyziologických a patologických podmienok

Duration: 1. 7. 2020 - 30. 6. 2024
Program: APVV
Project leader: RNDr. Račeková Enikö CSc.
Annotation:The regulatory mechanisms of postnatal neurogenesis in the olfactory neurogenic area of the mammalian brain - the subventricular zone (SVZ), rostral migratory stream (RMS) and olfactory bulb (OB) are still not fully understood. The project is focused on investigation of neurogenesis regulation via neurotransmitters nitric oxide and serotonin in this neurogenic region under physiological conditions and in rat model of depression. We intend to reveal neuronal circuits of nitric oxide producing neurons localized within the rat RMS, which should contribute toward the understanding of neuronal regulation of postnatal neurogenesis. To date, the association between decreased serotonin levels due to depression and reduced neurogenesis has been demonstrated only in the hippocampus. Our experiments are aimed to investigate the link between depression, altered serotonin regulation and neurogenic processes in the olfactory neurogenic area. Detailed analysis of integral components of microenvironment in the SVZ in animals with induced depression enables us to reveal the processes of regulation of neurogenesis in pathologically altered conditions. New knowledge in this area could potentially reveal promising targets for novel therapies aimed to disorders associated with changes in adult neurogenesis.

Dyad remodelling in cardiomyocytes in experimental therapy of failing heart

Reorganizácia diád kardiomyocytov pri experimentálnej terapii zlyhávajúceho srdca

Duration: 1. 1. 2021 - 31. 12. 2024
Program: VEGA
Project leader: RNDr. Zahradníková, ml. Alexandra PhD.
Annotation:Heart failure is a prominent cause of death in contemporary society. The development of heart failure is accompanied by marked changes in the energetics of the myocardium. Therapy by a cocktail of B vitamins, targeted at mitochondrial energetics, showed a promising cardioprotective effect on the development and progression of heart failure. However, it is not known to what extent does the protection result from remodelling of the calcium signalling systems. Our aim is to identify the relationship between the structural dynamics of dyads, the quality of excitation-contraction coupling, and the changes of junctophilin expression in a model of cardiac pressure overload in mouse. In line with the translational potential of metabolic therapy, we will also evaluate its effect in the context of standard heart failure medication (ß-blockers, ACE inhibitors). The results will foster the understanding of maladaptive processes of cardiac hypertrophy during emergence, development and therapy of heart failure at the cellular and molecular level.
Project web page:http://confolab.sav.sk/ovsb/projekty/aktivne-projekty/vega-2-0182-21/

rickcoxdiag - Rickettsiae and Coxiella burnetii, bacterial triggers of the “mysterious“ diseases

Rickettsiae a Coxiella burnetii, bakteriálne spúšťače

Duration: 1. 1. 2019 - 31. 12. 2022
Program: VEGA
Project leader: RNDr. Sekeyová Zuzana PhD.
Annotation:In certain types of diseases with no clear way of developing are bacteria considered as "triggers" of various ills. They are referred to a number of data indicating a synergistic action of bacterial infections on the human body. Moreover, certain bacteria, R. prowazekii from rickettsiae and C. burnetii, were included among the potential bio-terrorist weapons. The detection of the causal causes of bacterial infections in neuropathies (rickettsiae) and cardiovascular diseases (C. burnetii), on the serological, molecular and transkriptomic basis, has therefore a major medical importance and is a scientific challenge. We will concentrate our forces on the clarification of the pathomechanisms of their interaction at the cellular level; reveal specific patterns and abnormal growth of infected cells, forthcoming disorders due to rickettsial and/or Q fever infection, as well as the structure, i.e. genes coding for "pathologically responsible" proteins. Our knowledge will subsequently be put in a diagnostic practice.
Project web page:https://evega.minedu.sk/e-vega/, https://evega.minedu.sk/e-vega/(S(u0rnwgvty5vt3i554hz5sb2g))/users/Projekty_zoznam_0001.aspx

EVAgoEAST - Improvement of the biotechnological research potential of the Biomedical Research Center of the Slovak Academy of Sciences to combat the pandemic COVID-19 in synergy with the European Virus Archive of Global Importance supported by the H2020 program

Rozvoj biotechnologického výskumného potenciálu Biomedicínskeho centra SAV na boj proti pandémii COVID-19 v synergii s Európskym vírusovým archívom globálneho významu podporovaným programom H2020

Duration: 1. 4. 2020 - 30. 6. 2023
Program: Štrukturálne fondy EÚ Výskum a inovácie
Project leader: RNDr. Zelník Vladimír CSc.
Annotation:The COVID-19 pandemic represents a situation that we have not faced in recent history, and its great challenge is to define measures to manage it and to develop strategies to avert further potential global health threats in the form of emerging infectious diseases. The European Virus Archive GLOBAL (EVAGLOBAL) project, supported by the EU's H2020 program, has set as one of its main objectives the improvement of the availability of viruses and their derived products to the scientific community and thus the acceleration of global virological research. An important mission of this consortium is to be a responsive leader in times of viral epidemics. Part of the activities of the Biomedical Center of the Slovak Academy of Sciences (BMC) within the EVA GLOBAL project is the isolation and provision of Slovak strains SARS-CoV-2 to the scientific community and other institutions on a global scale. analysis and multiplication with the aim of making them available through the EVA GLOBAL depository 2) development of BTL BMC SAS activities by creating a backup virus depository with a modern storage and registration system and preparation of virus-derived products for diagnostic, therapeutic and preventive purposes. ) at the detached workplace of the BMC SAS in Šarišské Michaľany, where a new site of the virus archive will be created and where methods for preparation of virus-derived products and standardized methods for determining the biocidal activity of disinfectants will be developed and validated. in the form of five professional articles and presentations to the public, the creation of two new jobs and investment in IT for healthcare related to COVID-19. The extension of the virus archive to BTL SAV will support BMC SAV within the EVA GLOBAL project in the fight against the COVID-19 pandemic and at the same time significantly strengthen the possibilities of BTL SAV in Šarišské Michaľany in developing human potential in high value-added research with direct international impact, thus supporting their integration into the European Research Area.

ExoTREAT - Suicide gene therapy mediated by mesenchymal stromal and pancreatic tumor cell-excreted extracellular vesicles in the treatment of pancreatic ductal adenocarcinoma

Samovražedná génová terapia sprostredkovaná exozómami z mezenchýmových stromálnych a pankreatických nádorových buniek v liečbe duktálneho adenokarcinómu pankreasu

Duration: 1. 7. 2021 - 30. 6. 2025
Program: APVV
Project leader: Mgr. Cihová Marína PhD.
Annotation:Despite the advances in pancreatic cancer research, the survival of pancreatic ductal adenocarcinoma (PDAC) patients remains low. Innovative therapies based on novel principles are therefore urgently needed. Tumor tropic behavior of mesenchymal stromal cells (MSCs) led to the development of prodrug cancer suicide gene therapy. MSCs with integrated suicide gene yeast cytosine deaminase::uracilphosphoribosyl transferase (yCD::UPRT) proved to be an effective tool in the eradication of several deadly cancers in preclinical studies. The attractiveness of this approach lies in eliminating the systemic toxicity of 5-fluorouracil (5-FU) by non-toxic prodrug 5- fluorocytosine (5-FC) administration, which is metabolized into toxic 5-FU intracellularly. We found that yCD::UPRT gene-transduced MSCs release extracellular vesicles that carry mRNA of the suicide gene in their cargo. Their sustained intracellular killing activity and prolonged temperature stability would assign them to “off-the-shelf” medication. The development, characterization, and safety assessment of this innovative vesicle-mediated PDAC- targeted therapy will be the main objective of the proposed project. PDAC cell lines and primary pancreatic tumor cells will be treated with suicide gene vesicles to determine the most efficient approach both in vitro and in vivo. The most relevant preclinical models - patient-derived organoids and xenografts, which closely mimic the patient tumor complexity, will be used for these purposes. Moreover, PDAC cell-released extracellular vesicles, known to form a pre-neoplastic niche, will be studied and characterized. Combining gene therapy with standard of care drugs administered in MSC- and tumor-vesicles will be assessed to prevent metastases formation. We believe that the new opportunities bought by scientific knowledge and multidisciplinary collaboration will help us to achieve the project's goals and potentially improve the survival of patients with PDAC.

Investigation of the regulatory effect of serotonin on neuroblast migration in the neurogenic region of the adult brain

Skúmanie regulačného účinku sérotonínu na migráciu neuroblastov v neurogénnej oblasti mozgu v dospelosti

Duration: 1. 1. 2022 - 31. 12. 2024
Program: VEGA
Project leader: RNDr. Martončíková Marcela PhD.
Annotation:In the subventricular zone (SVZ) of the lateral ventricles of the mammalian brain, new neurons are generated throughout life. They migrate for a long distance via the rostral migratory stream (RMS) to the olfactory bulb (OB) where they differentiate and integrate to neuronal circuits. Understanding the mechanisms governing the migration is important for the potential use of neural precursors for therapeutic purposes. Neuroblasts in the SVZ-RMS-OB migrate along blood vessels and the migration is regulated by brain-derived neurotrophic factor – BDNF produced by endothelial cells of blood vessels. Recent studies suggest the effect of the neurotransmitter serotonin on the proliferation and migration of neuroblasts in the SVZ-RMS-OB. The aim of our project is to map the localization of serotonin receptors in the SVZ-RMS-OB and to examine the effects of serotonin on neuroblast migration and the possible link between BDNF and serotonin regulatory systems in the regulation of migration in vitro on the SVZ-RMS-OB explant.

Interrelationships between endocrine and mental characteristics of women in reproductive age

Súvislosti medzi endokrinnými a psychickými charakteristikami žien v reprodukčnom veku

Duration: 1. 1. 2019 - 31. 12. 2022
Program: VEGA
Project leader: prof. PharmDr. Ježová Daniela DrSc.

BIOFORD - Systemic public research institution - biobank for cancer and rare diseases

Systémová verejná výskumná infraštruktúra – biobanka pre nádorové a zriedkavé ochorenia

Duration: 1. 6. 2020 - 30. 6. 2023
Program: Štrukturálne fondy EÚ Výskum a inovácie
Project leader: RNDr. Gašperíková Daniela DrSc.

Study of alternative ways of genome-wide polygenic risk score calculations for the estimation of individual genetic predispositions to complex multifactorial diseases

Štúdium alternatívnych spôsobov výpočtov polygénových rizikových skóre na hodnotenie individuálnych genetických predispozícií ku komplexným multifaktoriálnym ochoreniam

Duration: 1. 1. 2020 - 31. 12. 2022
Program: VEGA
Project leader: RNDr. Radvánszky Ján PhD.
Annotation:In the field of genomic analyses, the assessment of genomic background of individual patients, in terms of complex multifactorial diseases, is an issue of worldwide interest. Main attention is paid to the design of appropriate calculations of genome-wide polygenic risk scores to determine predispositions to these diseases. We believe that the original, and so far unique, components of the present project are: 1) evaluation of individual patients by stratifying genomic risk factors to discrete biological pathways, specifically calculating partial risk scores for individual pathways; 2) in the context of genomic data from family members, using segregation analyzes. We selected ulcerative colitis, psoriasis and rheumatoid arthritis as model diseases. We plan to study them on multi-generation families, where all these diseases occur separately in different members belonging to different generations, but also in families where these diseases occur at one member comorbidly.

HNOSES - Study of biological effects of H2S/NO/selenium products and molecular mechanisms of their actions

Štúdium biologických účinkov produktov H2S/NO/selénovej interakcie a molekulárne mechanizmy ich pôsobenia

Duration: 1. 7. 2020 - 30. 6. 2024
Program: APVV
Project leader: RNDr. Ondriaš Karol DrSc.
Annotation:Reactive sulfur (RSS), nitrogen (RNS) and selenium species (RSEs) are groups of simple chemical molecules of radical or non-radical nature, which interact with cellular components and thereby influence various biological processes. The study of biological effects of RSS, RNS and RSeS and their mutual interactions is important for the understanding of their biological roles, moreover for the potential application of these species in medicine. Our studies of the reactive species interaction in the last 3 years showed that: - products of hydrogen sulfide (H2S) and polysulfides (H2Sn, n≥2) interaction with nitric oxide (NO) or selenium compounds (R-Se) significantly affect oxygen radicals concentrations, hydroperoxide cleavage, DNA damage, rat blood pressure and tension/relaxation of isolated aorta. - H2S and H2S2 interact with tetracycline antibiotics, mainly doxycycline (DOXY) and thereby produce/inhibit superoxide and hydroxyl radicals and induce/inhibit DNA damage These findings imply the possibility that reactive oxygen species (ROS) and other H2S/NO/R-Se interaction products affect (patho)physiological functions in living organisms. In the project´s aims we will build on the previous findings and investigate following new hypotheses: 1) Do mixtures (H2Sn/R-Se, H2Sn/R-Se/NO alebo H2Sn/DOXY) produce ROS or other biologically active compounds? 2) Are these products responsible for production/inhibition of radicals, cleavage of hydroperoxides and induction/inhibition of DNA damage? 3) Do interaction products affect ferroptosis or intracellular calcium concentration in cells? 4) Do these products affect rat blood pressure, arterial pulse waveform and tension of isolated arteries? The aim of this project is to investigate the chemical biology, activity and effects of the interaction products on cellular, organ and whole-organism level. These findings may contribute to the development of novel therapeutic interventions based on the modulation of cellular redox biology.

Study of the genetic background of variable severity of Alkaptonuria using genomic approach.

Štúdium genetického pozadia variabilnej závažnosti alkaptonúrie za použitia genomických analýz.

Duration: 1. 1. 2020 - 31. 12. 2022
Program: VEGA
Project leader: Mgr. Zaťková Andrea PhD.
Annotation:Genome sequencing can be used for deeper analysis of the genetic background of the disease, for possible studies of the phenotype and genotype correlation. Alkaptonuria (AKU) is caused by mutations in the homogeneisate-1,2-dioxygenase (HGD) gene, while due to the metabolic block homogeneous acid (HGA) is accumulated in the form of so called ochronotic pigment, causing painful multisystemic disease mainly affecting the cartilage of large joints and spinal column (disease-related arthropathy). Recently, we reported different levels of HGA in the urine of the patients that carry mutations causing different residual HGD enzyme activity, while this was not reflected directly at the phenotypic level by the severity of the disease in the mutation carriers. However, there is a marked variability in AKU patients, even within one family, thus other genetic factors are believed to affect the manifestation and progress of the disease. Our project will focus on identification of such variants.

GlycoOFFviro - The study of HCMV virokine interactions underlying regulation of the immunological synapse for the development of a novel immunotherapeutic concept based on viral tricks

Štúdium interakcií HCMV virokínov zapojených do imunologickej synapsy pre vývoj nového imunoterapeutického konceptu založeného na vírusových trikoch.

Duration: 1. 1. 2022 - 31. 12. 2025
Program: VEGA
Project leader: Mgr. Nemčovičová Ivana PhD.
Annotation:The molecular interactions regulating immune response take place in a nanoscale gap between T cells and antigen presenting cells, termed the immunological synapse. If these interactions are dysregulated, the host is susceptible to pathogens or tumor escape at one extreme and autoimmunity at the other. Treatments targeting the synapse have helped to establish immunotherapy as a mainstream element in cancer treatment. The novelty of our concept is to look at the molecules of immunological synapse that cytomegalovirus uses to turn down the immune system to figure out how to develop a new biotherapeutic drug. Within the project, we will investigate several HCMV virokines that function on NK and T cells and how they act in healthy and diseased states. The aim is to produce a detailed picture of their molecular architecture and function and therefore to serve as a molecular-level blueprint for rationalized design of bioimmunotherapeutics. This project is the logical continuation of our long-term joint initiative.

Study of pro-metastatic functions of carbonic anhydrase IX, relationship between CA IX and mucins and hypoxic microenvironment in pancreatic cancer.

Štúdium prometastatických funkcií karbonickej anhydrázy IX, jej vzťahu k mucínom a hypoxického mikroprostredia v rakovine pankreasu.

Duration: 1. 1. 2019 - 31. 12. 2022
Program: VEGA
Project leader: Mgr. Švastová Eliška PhD.
Annotation:Pancreatic cancer especially intraductal papillary mucinous neoplasms (IPMNs) are characterized by aberrant expression of different types of mucins. Although the overall prognosis for patients with IPMNs is better than it is for pancreatic ductal adenocarcinoma (PDAC) a subset of patients develops invasive tumors. Carbonic anhydrase IX is hypoxia induced protein whose expression, in many cancers, is associated with higher metastatic potential and poor prognosis of patients, also in cohort of patients with pancreatic ductal adenocarcinoma with lower survival. Genevestigator analysis revealed co-expression of CA9 with mucins (e.g. MUC1, MUC5AC) in IPMNs that progress from adenoma to carcinoma. Characterization of CA IX - mucins relationship and their role in epithelial-mesenchymal transition in pancreatic cancer and the impact of CA IX-related tumor microenvironment on pancreatic cancer progression is essential for adequate therapeutic strategies to overcome this lethal disease.
Project web page:https://www.minedu.sk/data/att/13859.pdf

PANDIAREG - Investigating the role of GPR180/CTHRC1 signalling in regulation of pancreatic B cell function and pathogenesis of diabetes

Štúdium úlohy GPR180/CTHRC1 signalizácie v regulácii funkcie β buniek pankreasu a patogenéze diabetu

Duration: 1. 9. 2022 - 31. 8. 2025
Program: SASPRO
Project leader: Mgr. Balážová Lucia PhD.

Effect of electrical stimulation on regeneration of injured neural pathways.

Účinok elektrickej stimulácie na regeneráciu poškodených nervových dráh.

Duration: 1. 1. 2020 - 31. 12. 2023
Program: VEGA
Project leader: RNDr. Gálik Ján CSc.
Annotation:Despite intensive efforts of researchers and clinicians, there is no, so far, an effective therapy for the recovery of nervous tissue after ischemic or traumatic injury. None of the few clinically approved procedures leads to satisfactory results. The aim of proposed project is to increase the effectiveness of current therapies by combining them with sustained electrical stimulation of injured tissue, which can facilitate regeneration of axons and provide guidance for their growth. We will test the possible synergistic effect of sustained stimulation with surgical, pharmacological and physical interventions.

Virulence factors of tick-borne encephalitis virus and their role in transmission via tick vector

Úloha faktorov virulencie vírusu kliešťovej encefalitídy v prenose kliešťami

Duration: 1. 1. 2019 - 31. 12. 2022
Program: VEGA
Project leader: RNDr. Koči Juraj PhD.
Annotation:Tick-borne encephalitis virus (TBEV) causes one of the most severe neurodegenerative disorders transmitted by ticks. So far, studies on disease pathogenesis have focused primarily on a host and there is very little information on interactions between the virus and its vector although they are integral part of an enzootic cycle of the virus. Therefore, this proposal is focused to analyse interactions between TBEV strain Hypr and a tick Ixodes ricinus. By using a reverse genetics approach, viruses with a mutated domain III of protein E and incorporated reporter gene will be developed. Dynamics of transfer and interaction of recombinant viruses with ticks will be investigated using in vitro tick feeding system. Obtained results and developed tools will provide invaluable information on virus virulence factors and their role in establishing infection, dissemination and transfer within ticks. In addition, our studies will significantly contribute to research of other tick-borne viruses.

The role of mitochondria in progression of colorectal cancer

Úloha mitochondrií v progresii kolorektálneho karcinómu

Duration: 1. 1. 2021 - 31. 12. 2024
Program: VEGA
Project leader: RNDr. Tyčiaková Silvia PhD.
Annotation:Mitochondria respond to energetic needs and stress stimuli by adapting their structure and function. Their morphology is changed in process of fusion and fission. Tumor cells maintain reprogrammed energetic metabolism towards aerobic glycolysis, display smaller mitochondria and activated dynamin-related protein 1, responsible for mitochondrial fission. Bioenergetic function of mitochondria is usually supressed in tumors. Our preliminary study shown that pro-apoptotic effect of drugs includes enhanced mitochondrial fission in colorectal cancer (CRC) cells. We suppose that mitochondrial morphology and size, changed by fusion and fission affects progression and invasivity of tumor cells. Therefore, we aim to study correlation among mitochondrial fission, status and aggressive phenotype of CRC-derived cells. We will examine the effect of Drp1 knockdown on mitochondria as well as the effect of overexpression of proteins responsible for mitochondrial fusion MFN1/2 in CRC cells in comparison to healthy cells.

DRPGE - The role of DNA repair proteins in gene repression

Úloha proteínov DNA opravy v génovej represii

Duration: 1. 7. 2022 - 30. 6. 2026
Program: APVV
Project leader: Ing. Čipáková Ingrid PhD.

Role of the hydrogen sulfide in remodelation cytoskeleton in colorectal carcinoma cells; impact on activity of taxanes

Úloha sirovodíka pri remodelácií cytoskeletu v bunkách kolorektálneho karcinómu; vplyv na pôsobenie taxánov

Duration: 1. 12. 2019 - 31. 12. 2022
Program: Iné projekty
Project leader: prof. Ing. Križanová Oľga DrSc.

Effects of physical activity on psychological state of obese adolsecents

Vplyv fyzickej aktivity na psychiku u obéznych adolescentov

Duration: 1. 1. 2019 - 31. 12. 2022
Program: VEGA
Project leader: prof. MUDr. Ukropcová Barbara PhD.

Effects of natural polyphenol and nonsteroidal anti-inflammatory drug combination therapy on the tumor microenvironment

Vplyv kombinovanej terapie prírodnými polyfenolmi a nesteroidnými protizápalovými liečivami na nádorové mikroprostredie

Duration: 1. 1. 2021 - 31. 12. 2024
Program: VEGA
Project leader: RNDr. Grossmannová Katarína PhD.

Effect of combinaion therapy with carnosine on tumorigenesis in colorectal carcinoma models

Vplyv kombinovanej terapie s karnozínom na proces tumorigenézy v modeloch kolorektálneho karcinómu

Duration: 1. 1. 2020 - 31. 12. 2023
Program: VEGA
Project leader: RNDr. Baráthová Monika PhD.
Annotation:Continuous search for new approaches and treatment strategies is essential in the treatment of cancer. Multiple drug combination therapy simultaneously involves several cellular mechanisms in order to make treatment more effective, reduce toxicity and prolong patient life. New therapeutic approaches use not only the combination of anticancer drugs but also natural substances. By ccombination therapy with carnosine and chemotherapeutic agents we want to affect mitochondrial mechanisms - bioenergetics, quenching of active forms of oxygen, indirectly also stability of HIF1a subunit, and use the impact of carnosine on pH regulation in tumor cells expressing CA IX. Together with chemotherapeutics, we want to analyze the impact of such combinations on proliferation, migration, metastatic potential as well as on the chemotherapy-resistant cancer stem cell pathways. The aim of the project is also to use 3D models of cell cultivation in spheroids and to introduce a method of forming microtumors from clinical samples.

The effect of neuropeptides involved in food intake regulation on neuritogenesis and synaptogenesis

Vplyv neuropeptidov súvisiacich s príjmom potravy na neuritogenézu a synaptogenézu

Duration: 1. 1. 2021 - 31. 12. 2023
Program: VEGA
Project leader: Mgr. Bačová Zuzana PhD.

Influence of NS1 protein and influenza virus load on the pathogenesis and innate immune response in brains, hearts and spleens of infected mice

Vplyv proteínu NS1 a infekčnej dávky vírusu chrípky na patogenitu a vrodenú imunitnú odpoveď v mozgoch, srdciach a slezinách infikovaných myší

Duration: 1. 1. 2020 - 31. 12. 2023
Program: VEGA
Project leader: doc. RNDr. Betáková Tatiana DrSc.
Annotation:Despite the widespread application of vaccination programs, influenza viruses are still among the most harmful human pathogens. Influenza encephalopathies, encephalitis lethargica and Reye´s syndrome are rare, but serious diseases that manifest with influenza infection. High pathogenic strains are able to spread to the brain, liver and other organs. NS1 protein counteracts the induction of antiviral response. Our preliminary data shows, that the immune response was activated in the brain and spleen of mice infected with low pathogenic influenza virus despite of fact that virus was not detected in these organs. The main aim of this project is to investigate the influence of virus pathogenicity as well as NS1 protein on the spread of the virus into the brain, heart and spleen of infected mice and on their ability induce RIG-1-like receptor signaling pathway in these organs. We also suggest that the cells of immune system like macrophages, neutrophils, etc. play more important role in pathogenesis.

CEMEA - Centre of Excellence for advanced materials application

Vybudovanie Centra pre využitie pokročilých materiálov Slovenskej akadémie vied

Duration: 1. 7. 2019 - 30. 6. 2023
Program: Štrukturálne fondy EÚ Výskum a vývoj
Project leader: RNDr. Csáderová Lucia PhD.

SYNDEAF - Identification of novel genetic variants in syndromic hearing loss by whole exome sequencing

Vyhľadávanie nových génových variantov syndrómových porúch sluchu pomocou celoexómového sekvenovania

Duration: 1. 7. 2021 - 30. 6. 2025
Program: APVV
Project leader: RNDr. Gašperíková Daniela DrSc.

OCHRANA COVID-19 - Research of a barrier fabric for a community face half mask and protective clothing

Výskum bariérovej textílie do komunitnej tvárovej polmasky a ochranného odevu

Duration: 1. 7. 2021 - 30. 6. 2023
Program: APVV
Project leader: RNDr. Zelník Vladimír CSc.
Annotation:The main goal of the research project is fundamental innovation and broadening the range of personal protective equipment in short supply, designed for protection against biological carriers of infectious diseases. Objective of the project solution is research in the field of preparation of a barrier fabric with enhanced functional properties preventing spread of bacteria and viruses. Strong inhibition and bactericidal effect of the barrier fabric will be imparted by application of progressive technological finishes using low-temperature atmospheric plasma and subsequent creating of nanostructured surfaces by a form of a thin nanolayer with antimicrobial properties, namely using antimicrobial nanosol with incorporated silver nanoparticles Ag+. Result of the project solution will be a barrier fabric with enhanced functional properties (filtration efficiency: min 70% for particles 3 ± 0,5 μm, pressure difference of the material ≤ 70 Pa/cm2, breathing resistance: inbreath max. 2,4 mbar, outbreath max. 3 mbar) with subsequent application in the prototype of the community face half mask and in the prototype of the community protective clothing. The proposed project is a reaction on a negative situation with shortage of personal protective equipment, which was manifested in the first wave of COVID-19 pandemic. Thus, realization of the project will create material presumptions for ensuring certain level of population protection on depression of the epidemic and/or pandemic and preventing spread of infections and viruses in the population.

RICTRANSPROT - Investigation of the Host – Parasite, Cell - Rickettsia Relationship, Monitored by Transcriptomic and Proteome Studies.

Výskum hostiteľsko – parazitických, bunkovo - Rickettsiových vzťahov, monitorovaných pomocou transcriptomických a proteomických štúdií.

Duration: 1. 7. 2020 - 30. 6. 2024
Program: APVV
Project leader: RNDr. Sekeyová Zuzana PhD.
Annotation:In recent years, the host – parasite relationship is increasingly monitored by transcriptomic and proteome studies. It is obvious, that host–pathogen interactions involves protein expression changes in both actors the host cells and the rickettsial pathogen. An understanding of the nature of these interactions at the proteomic level will provide insight into metabolic processes, critical regulatory events of the host cells as well as the mechanism of pathogenesis of rickettsioses. We aim to study these regulatory events, control mechanisms, which underlie not only the functioning of individual cells but also the processes of differentiation and development, protein synthesis, processing, folding or degradation, both in infected cells and Rickettsiae. We will use premium, the state-of-the-art proteomic technologies enabling of measuring several thousands of proteins within a few hours, they will permit us to significantly increase the analytical depth as well as coverage in complex proteome analyses. We will be interested in the function of proteins with respect to the course of protein expression at which can be regulated the flow of information from the genome to the Proteome, in both Rickettsiae and the infected cells. We aim to search for transcriptional changes in infected cells observed following exposure to Rickettsiae and to a nutrient stress that will be verified, starting from amplified cDNA and total RNA as templates, means we will apply an approach that has great potential for the study of mechanisms behind the virulence and intracellular survival of members of the genus Rickettsia.
Project web page:https://portal.apvv.sk/index.aspx?Module=Application&Page=Project&MenuID=287&ProjectID=19604

imunocheck - Harnessing the immunological mechanisms in various subtypes of B cell lymphoma

Využitie imunologických mechanizmov v rôznych subtypoch B-bunkových lymfómov

Duration: 1. 7. 2020 - 30. 6. 2024
Program: APVV
Project leader: RNDr. Cholujová Dana PhD.
Annotation:Malignant lymphomas are mostly incurable blood cancers affecting different white blood cells formed in lymphoid structures, including the lymph nodes, spleen, and bone marrow. They have different origin in B cell development with different biological properties and clinical aggressiveness. This tumor cells compete for space to grow within tumor microenvironment by affecting the surrounding healthy cells in the bone marrow to suppress patient immunity. The purpose of this proposal is to better understand tumor and tumor-driven immune changes and evaluate their phenotypic differences and functional complexity by comprehensive state-of-art technology mass cytometry (CyTOF). Furthermore, we will study the immunological mechanisms “immune checkpoints” that can be targeted in malignant lymphoma. The better understanding of pathogenesis of B-cell malignancies will lead to new therapeutic strategies directed against tumor and immune cells to completely eradicate tumor in individual patient.

Nanomedical approach to fight pancreatic cancer via targeting tumor-associated carbonic anhydrase IX

Využitie nanomedicíny v boji proti rakovine pankreasu prostredníctvom zacielenia nádorovo- asociovanej karbonickej anhydrázy IX

Duration: 1. 7. 2021 - 30. 6. 2025
Program: APVV
Project leader: RNDr. Csáderová Lucia PhD.

GenoMicrosat - Development and testing of molecular and informatic tools for effective characterisation and interpretation of clinically relevant microsatellite repetitive motifs from genomic data

Vývoj a testovanie molekulárnych a informatických metód na efektívnu charakterizáciu a interpretáciu klinicky relevantných mikrosatelitových repetitívnych motívov z genomických dát

Duration: 1. 7. 2019 - 30. 6. 2023
Program: APVV
Project leader: RNDr. Radvánszky Ján PhD.
Annotation:The proposed project is based on the recognition of facts that: (i) the genomic material of each person contains an immense amount of health-related information; ii) the usability of these genomic information depends on our ability to identify genomic variants; iii) microsatellite motifs (STRs) play an important role in various aspects of physiological and pathological processes of our organisms. Despite that STRs represent the most variable loci of our genome, their variability is still very poorly described. In particular this is caused by a lack of tools allowing their accurate and comprehensive evaluation from large-scale genomic data sets. The aim of our project is, therefore, to examine specific aspects of possibilities of STR motifs characterisation from whole-genome sequence data with simultaneous development and validation of molecular-genetic approaches and bioinformatics tool capable of processing data derived from massively parallel sequencing. From these data thedeveloped tool should be able to extract clinically relevant information, such as the numbers and exact sequence of repetitions of particular alleles, the phase of individual parts of complex motifs, signs of motif instability, and the presence of possible pathological expansions of repeat numbers. As a clinical model we chose two main patient groups: 1) patients with a molecularly confirmed diagnosis of disease caused by expansions of STR motifs (myotonic dystrophy type 1 and 2, Huntington's disease and Fragile X syndrome); 2) patients with Lynch syndrome, in whom instability of microsatellite motif is an important clinical biomarker. Based on the generated data as well as on data derived from appropriate conventional validation methods and other already available tools, we plan to perform comprehensive statistical validation and characterization of the reliability, accuracy and practical applicability of our newly developed tool in specific areas of biomedicine and personalized healthcare.

BIOTREAT - Development of bioimmunotherapeutics inspired by viral tricks: TREATing despite the TRICKs

Vývoj bioimunoterapeutík inšpirovaný vírusovými trikmi: Liečenie aj napriek trikom

Duration: 1. 7. 2020 - 30. 6. 2024
Program: APVV
Project leader: Mgr. Nemčovičová Ivana PhD.
Annotation:The immunotherapy is now one of the hottest areas in research, however, our aim is to work on immunotherapy that set out in novel direction – by tricking the body’s own defenses inspired by viral tricks into fighting the enemy within. Our main goal is to look at the molecules that cytomegalovirus uses to turn down the immune system to figure out how to develop a new biotherapeutic drug to treat both viral and autoimmune diseases. Within the project, we will investigate two important viral proteins (UL141 and UL144) that function on NK and T cells and how they act in both healthy and disease states. The aim is to produce a detailed picture of their molecular architecture and function and therefore to serve as a molecular-level blueprint for rationalized design of bioimmunotherapeutics and this will be tested by computational methods in parallel to in vitro biological testing on both normal and tumor cells. The determination of such factors regulating receptor and ligand expression on the cell surface and to identify a potentially inhibitable interaction between these cellular restriction factors and a viral antagonist will allow for a better understanding of the role of these viral proteins in immune responses and how these pathways can be manipulated for therapeutic intervention. This project is the logical continuation of our previous work and an existing joint collaborative initiative in dealing with development of bioimmunotherapeutics.

Development of patients derived xenografts models and their utilization for personalized treatment of uveal melanoma

Vývoj modelov xenotransplantátov z pacientských tkanív a ich využitie na personalizáciu liečby malígneho melanómu uvey

Duration: 1. 1. 2021 - 31. 12. 2024
Program: VEGA
Project leader: Ing. Demková Lucia PhD.
Annotation:Uveal melanoma (UM) is the most common intraocular malignant tumor in adults, metastasizing in 50% of patients. Despite reliable prognostic markers, this malignancy is associated with a high mortality rate due to tumor cell resistance. Treatment development is limited by the poor availability of appropriate preclinical models. Among the most valuable are those derived from patients' tumors, so-called patient-derived xenografts (PDX), on the development of which the presented project will focus. In UM pathogenesis crucial role plays epigenetic deregulation. Due to their reversible nature epigenetic inhibitors are in the spotlight of current clinical research. We hypothesize that they can sensitize resistant UM cells and, therefore, might considerably improve the therapeutic index of signaling pathways inhibitors. PDX models will be applied to test the most effective drug combinations. They will allow the use of a personalized approach for adjuvant therapy development to prevent metastasis in high-risk patients.

PhenoTOOL - Development of novel diagnostic and predictive high-dimensional immunophenotyping tool for hematological malignancies

Vývoj nového diagnostického a prediktívneho vysokodimenzionálneho imunofenotypizačného nástroja pre hematologické malignity

Duration: 1. 11. 2019 - 31. 12. 2022
Program: Iné projekty
Project leader: RNDr. Jakubíková Jana PhD.
Annotation:Immunophenotyping is currently one of the fundamental pillars for the diagnosis, classification, staging and monitoring of hematological malignancies, such as leukemia and lymphoma. In this study, we will take an advantage of novel high-dimensional technology mass cytometry that to develop novel diagnostic and predictive approach with complex multi-dimensional immunophenotyping profiles and overall immune cell profiling to diagnose, classify, stage and monitor of the therapy response in patients with leukemia, lymphoma and multiple myeloma.

- The development of translationally relevant regenerative and reparative strategies after spinal cord trauma

Vývoj translačne relevantných regeneračných a reparatívnych stratégií po traumatickom poranení miechy

Duration: 1. 7. 2020 - 30. 6. 2024
Program: APVV
Project leader: RNDr. Lukáčová Nadežda DrSc.
Annotation:The aim of this project is to investigate the regulatory impact of clinically approved/tested anti-inflammatory drugs on the polarization of M1/M2 macrophages, which play a key role in activation of pro-regenerative molecules following traumatic spinal cord injury and design translational strategies that have the potential to improve functional recovery of experimental animals. We propose to examine the protein profile of selected spinal cord regions (lesion site, above and below the site of injury) after Th9 compression and application of methylprednisolone, atorvastatin, siponimod and VX-210 in acute/subacute phase of spinal injury, and evaluate their neuroprotective potential. We intend to develop a new technology that allows local application of the most effective drug with a gradual, time-dependent release to the site of spinal cord lesion. We suggest, that drug with the most efficient anti-inflammatory and antioxidant effect in combination with VX-210 (an inhibitor of Rho activity) locally administered via magnetic nanoparticles, will make the spinal treatment more effective and support the regenerative potential of nerve tissue. We plan to stimulate the functional recovery of motor and sensory functions by physical rehabilitation and long-term application of a weak electric field at the lesion site. The neuroprotective effect of synergic action of proposed approaches will be evaluated by analyzes of the expression of pro-regenerative signal molecules, axonal outgrowth, inter-neuronal and neuromuscular junctions and functional recovery.

DITIMA - Development of unique TiMg composite dental implant

Vývoj unikátneho TiMg kompozitného zubného implantátu

Duration: 1. 7. 2021 - 30. 6. 2025
Program: APVV
Project leader: RNDr. Takáčová Martina PhD.
Annotation:Dental implants (Dis) become more affordable and sought solution across a globe, the will be in a place for longer periods and a need for maintenance will decrease. Titanium (Ti) and Ti alloys are the most widely utilized materials for production of DI. Even though Ti-based DI are used with a high success rate, two major issues have remained insufficiently resolved: the stress-shielding effect and their insufficient surface bioactivity. That pushes competition, progress and R&D in the related area further and brings a need for novel solutions, approaches and material concepts. The main aim of proposed project is a development of an innovative endosseous biomedical DI fabricated from the unique partially biodegradable Ti - magnesium (Mg) composite material. New DI will minimize the main drawbacks of the contemporary DI, while it maintains the mechanical performance and fatigue endurance of Ti-based references. An advantageous combination of the mechanical, fatigue, corrosion and biological properties of developed DI is owing to a special DI`s design, which reflects and takes advantage of Ti17Mg, the material it will be manufactured from. Ti17Mg is the experimental powder metallurgy material invented by project partners, which selectively exploits the advantages of both biometals. In the project a new DI will be designed and optimized, in order to reflect unique behavior and workability of Ti17Mg. Performance of DI will be assessed and optimized systematically in an environment, which simulates real-life conditions in a human body, including mechanical, fatigue and corrosion testing, and in-vitro and in-vivo biological evaluation using cell culture, small and large animal models. All assays will be carried out in accordance with related ISO specifications. It is anticipated that at the end of the project new innovative high value-added DI is available and pending for testing in a human body. Expectedly TRL 6 will be accomplished at the end of project.

The significance of the interaction between scaffolding proteins and subcellular organelles in neuronal cells: the role of oxytocin

Význam interakcie skafoldových proteínov so subcelulárnymi organelami v neuronálnych bunkách: úloha oxytocínu

Duration: 1. 1. 2020 - 31. 12. 2022
Program: VEGA
Project leader: doc. RNDr. Bakoš Ján PhD.
Annotation:The origin, etiology and potential therapeutic approaches of neurodevelopmental disorders include genetic, molecular and pathophysiological aspects. The failure in oxytocin receptor signaling during the specific stages of the brain development is increasingly suspected as a cause of deficit in neuritogenesis, synaptogenesis and neuron connectivity. The explanation of these processes requires complex technical approaches allowing evaluation of the cytoskeletal proteins connecting neuronal cell membrane with the vesicular apparatus of the endoplasmic reticulum. The aim of the project is to clarify the role of oxytocin in the regulation of scaffolding proteins connecting to the endoplasmic reticulum in neuronal cells. The analysis of the expression of the SHANK family proteins, their visualization and co-localization with the subcellular organelles will be performed. Our understanding of the oxytocin action on the neuronal cell structure can contribute to the intervention in neurodevelopmental disorders.

The importance of interaction products of H2S with S-nitrosoglutathione/selenium derivatives in the regulation of cardiovascular hemodynamics and cardiac mitochondrial functions

Význam produktov interakcie H2S s S-nitrózoglutatiónom/selénovými derivátmi v regulácii srdcovocievnej hemodynamiky a funkcií srdcových mitochondrií

Duration: 1. 1. 2021 - 31. 12. 2024
Program: VEGA
Project leader: Mgr. Mišák Anton PhD.
Annotation:It is presumed that the cross-talk between H2S- and NO-mediated signaling pathways can play a role in the regulation of cardiovascular system (CVS). Furthermore, the interaction of H2S with selenium derivatives leads to the formation of new reactive (intermediate) products having a broad biological activity. The aim of this project is to extend results in this field by research on the hemodynamic effects of H2S and NO donors/selenium derivatives interaction products also in the context of cardiac mitochondrial functions. We will study the effect of these products on 35 hemodynamic parameters of normo/hypertensive rats and investigate the association of these effects with energy metabolism, specifically with mitochondrial bioenergetics and the functions of mitoKATP channels. These results may contribute to the understanding of the molecular mechanism of these interactions in the CVS, but they may also build a basis for applied studies leading to the use of the interaction products in medical practice.

Remote conditioning as a prevention and treatment of cerebral ischemia associated with hyper-inflammatory reaction (simulation of COVID-19)

Vzdialené kondicionovanie ako prevencia a liečba ischémie mozgu spojenej s hyper-zápalovou reakciou (simulácia COVID-19)

Duration: 1. 1. 2022 - 31. 12. 2024
Program: VEGA
Project leader: RNDr. Končeková Jana PhD.
Annotation:With the uprise of the virus SARS-CoV-2 pandemic, statistical prognoses for cerebrovascular disease are changing worldwide for the next decades. In more than a third of patients with COVID-19 neurological symptoms occurs in addition to respiratory problems. Infection-induced rapid release of pro-inflammatory cytokines and abnormal levels of coagulation factors in positive patients spikes the likelihood of thrombus formation and a risk of an acute stroke. It is reported, that at least 6% of COVID-19 positive patients have been diagnosed with a stroke, which appears to be an alarming number with the increase of infection incidence. However, the only one FDA accepted medical treatment in a clinic (tPA) has many limitations. Therefore, the increased demand for developing novel non-pharmacological therapies to elevate the tolerance to ischemia has been paying attention. Remote conditioning meets these conditions because of the ability to stimulate the endogenous protective mechanisms ensuring resistance to stroke.

Assessment of immune checkpoints in B cell malignancies

Zhodnotenie imunitných kontrolných bodov v B-bunkových malignitách

Duration: 1. 1. 2020 - 31. 12. 2022
Program: VEGA
Project leader: RNDr. Cholujová Dana PhD.
Annotation:Cancer immunotherapy is the idea of boosting the tumor-specific adaptive immune response instead of directlytargeting cancer cells. However, cancer cells can avoid immune surveillance by suppressing immunity throughactivation of specific inhibitory signaling pathways, referred to as immune checkpoints. Recently, the blockade ofcheckpoint molecules such as PD-1, PD-L1 and CTLA-4, with monoclonal antibodies targeting these checkpointmolecules has enabled the development of breakthrough therapies in oncology, with ongoing preclinical andclinical trial in B-cell malignancies. The overall objective of this proposal is to study B cell malignancies focusingon immune checkpoints molecules either in clonal tumor or immune accessory populations of tumormicroenvironment. Moreover, we will evaluate the effect of immune checkpoints neutralizing antibodies eitheralone or in combination (also with novel immunomodulatory drugs) to increase their efficacy as potential therapyfor patients with B-cell malignancy.

AMETHYST - Ameliorating Effects of Aging by Physical Exercise: Molecular, Metabolic and Structural Adaptations, Multi-Organ Integrative Approach

Zlepšenie prejavov starnutia pravidelným cvičením: multi-orgánový integratívny prístup k molekulovej, metabolickej a štrukturálnej adaptácii na cvičenie

Duration: 1. 7. 2021 - 30. 6. 2025
Program: APVV
Project leader: prof. MUDr. Ukropcová Barbara PhD.

Hepatic, lipid and cardiometabolic parameters changes in obese patients

Zmeny hepatálnych, lipidových a kardiometabolických parametrov u pacientov s obezitou

Duration: 1. 1. 2020 - 31. 12. 2023
Program: VEGA
Project leader: doc. MUDr. Penesová Adela PhD.
Annotation:Morbid obesity (MO, BMI >40 kg/m2) represents 2-3 times higher risk of diabetes, dyslipidemia, cardiovascular (CVS) diseases and non-alcoholic fatty liver disease (NAFLD). Our hypothesis is that even 10% reduction of body weight in MO will lead to improvement of liver parameters, hepatokines, LDL and HDL subfraction of lipoproteins, insulin sensitivity as well as to decrease of CVS risk. The aim of our study is to monitor the effect of intensive life style changes in MO patients and super morbid obesity (SO, BMI >50 kg/m2) on aforementioned parameters during 12 months. We have more than 270 obese, 23 MO and 28 SO patients in our registry. Intervention of life style will be individualized; dominant will be either physical activity and/or diet. Evaluation of hepatokines and lipid subfractions and analysis of anthropometry changes will contribute to understanding and extending the knowledge about the possibilities how to reverse the onset of NAFLD and KVS risk factors in MO and SO patients.

Projects total: 146