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Information Page of SAS Organisation

Project

Institute of Molecular Biology

International Projects

StruBioMol - Building learning and research capacities in the structure and functional analysis of biomolecules for the needs of biomedicine and biotechnology

Budovanie výukových a výskumných kapacít v štruktúrnej a funkčnej analýze biomolekúl pre potreby biomedicíny a biotechnológií

Duration: 1. 5. 2019 - 30. 4. 2022
Program: INTERREG
Project leader: Ing. Kutejová Eva DrSc.
Annotation:Biomedicine and biotechnology are modern science disciplines whose development contributes to improving the health of the population and improving the environment. Structural biology identifies the nature of serious illnesses and forms the basis for the design of potential drugs. It also allows you to search for potentially harmful substances and study their impact on the environment. What is lacking in our region is a common educational and scientific research base that would educate professionals capable of transferring modern knowledge in this area into practice. Within the framework of this project, we will set up a joint high-level educational and scientific research center for structural biology of doctoral students, scientists and practitioners in the region to build a broad scientific and technical base capable of making significant advances in research into biomedical and biotechnology applications to improve the quality of life in our region. We build on the experience of both partners as well as well-established international cooperation. The lectures and training seminars will be organized alternately in both workplaces to attract the widest community and to encourage mutual contacts between PhD students and researchers in Vienna and Bratislava with the perspective of further cooperation. The individual objectives of the project include: a) strengthening the long-term and sustainable basis for the development of structural biology in the region, measurable by the number of organizations using facilities and training facilities; b) education of university students, PhD students, researchers and practitioners, measurable number of lectures and practical courses and number of participants of prepared activities; (c) building a research center of excellence in structural biology for the study of human diseases, measurable by the number of devices purchased and their users. Long-term benefits will be the creation of a foundation for quality education, providing advice and leading research in the field of biomedicine and biotechnology, which will contribute to increasing the competitiveness of the region and attract the interest of foreign experts in co-operation and transfer of acquired knowledge into practice. These results will be reached through: 1) Training and staff exchanges among project partners 2) Innovative joint pilot projects base on the complementary cross-border equipment and expertise 3) Workshops and “Open Access” in order to raise awareness of the offered services These activities cannot be implemented without the cross-border cooperation as they depend on infrastructure and expertise on both sides of the border which cannot be easily replicated. This cooperation represents an outstanding opportunity for the cross-border region.
Project web page:http://www.imb.savba.sk/strubiomol

SuWaCer - Sustainable Water Reclamation Based on Ceramic Membrane Filtration

Trvalo udržateľná regenerácia vody založená na filtrácii keramickými membránami

Duration: 1. 4. 2020 - 31. 3. 2023
Program: Bilaterálne - iné
Project leader: Dr. Pangallo Domenico DrSc.
Annotation:Microplastics are a source of concern since they pose threats to aquatic species as well as human being. They not only contribute to accumulation of plastics in the environment, but due to absorption they can also contribute to spreading of micropollutants to the environment. Studies have shown that wastewater treatment plants are responsible for releasing micropollutants to the environment. Therefore, both detection and removal of microplastics from wastewater treatment plants are of paramount importance. Although the primary treatment process is efficient in removing microplastics of larger size, and microplastic fibers, it doesn’t remove small shaped microplastics. To remove very small shaped microplastic fragments, and to have the highest rate of microplastic removal, membrane technology is the best available technology. Organic membranes can be used for this purpose. Nevertheless, they are damaged easily. Ceramic membranes, on the other hand, have many advantages when compared to organic membranes such as higher abrasion resistance, chemical resistance, ability to be used at a very wide pH range (0 to 14), higher resistance to ozone and chloride, allowing the disinfection of water, and higher thermal resistance. In the light of this information, the aim of this project is to develop a robust durable ceramic membrane which will remove microplastics from secondary treated wastewater. To achieve this aim, tubular ceramic membranes with ultra and nanofiltration layers will be synthesized, and secondary treated wastewater will be treated with these membranes at lab and pilot scale for the removal of microplastics. The cyto-toxicity, genotoxicity and oxidative stress of micro/nanoplastics on human cells will be assessed, previously in vitro and then using the water of the wastewater pilot scale plant. In addition, also the antimicrobial properties of the membrane will be assessed, evaluating the microbial communities’ changes before and after the ceramic membrane treatment.

National Projects

CELLDIV - Asymmetric cell division during bacterial endospore formation

Asymetrické bunkové delenie počas tvorby bakteriálnej endospóry

Duration: 1. 7. 2019 - 30. 6. 2023
Program: APVV
Project leader: RNDr. Barák Imrich DrSc.
Annotation:Bacillus subtilis is an internationally-recognized model organism, whose physiology, biochemistry and genetics has been studied for many years. This organism is used for decades to study the mechanisms of cell division and especially differentiation process, called sporulation. During this process very resistant spores are developed which can lie dormant and then germinate. This resistance of spores presents threats as well as potential benefits to human health and welfare. Botulism and tetanus are infectious diseases transmitted by spores, while spores of Clostridium difficile are responsible for hospital-acquired infections that are harmful to patients and which are expensive to treat and eradicate. Spores of Bacillus cereus cause food poisoning and present a challenge to the food industry, while spores of B. anthracis, which causes anthrax, are a concern because of their potential use as agents of bioterrorism and biowarfare. In contrast, the durability of spores has seen their development for use in nano-biotechnology and as probiotics in the food industry. Meanwhile their temperature resistance and capacity to resist dessication is leading to the development of spores as delivery systems for vaccines. Despite intensive research in the field of B. subtilis sporulation, there are still crucial molecular details missing in the complex mosaic of this process. Probably one of the most controversial questions about the cell division of Bacillus subtilis, a rod-shaped bacterium, concerns the mechanism that ensures correct division septum placement – at mid-cell during vegetative growth but closer to one end during sporulation. This project proposes to study the mechanisms of asymmetric septum formation and early stages of sporulation in B. subtilis. The aims of the project should be achieved by employing wide range of molecular biology, biochemical, genetic, structural biology and most advanced microscopy techniques.

PreveLynch - -

Dlhodobý strategický výskum a vývoj zameraný na výskyt Lynchovho syndrómu v populácii SR a možnosti prevencie nádorov spojených s týmto syndrómom

Duration: 1. 1. 2020 - 30. 6. 2023
Program: Štrukturálne fondy EÚ Výskum a vývoj
Project leader: Dr. Pangallo Domenico DrSc.

Factors that influence mitochondrial nucleoid dynamics

Faktory ovplyvňujúce dynamiku mitochondriálneho nukleoidu

Duration: 1. 1. 2018 - 31. 12. 2021
Program: VEGA
Project leader: Ing. Kutejová Eva DrSc.

StainsAway - Colored stains on historical papers: biological and chemical characterization coupled with removal solutions

Farebné škvrny na historických papieroch: biologická a chemická charakterizácia spojená s ich odstraňovaním

Duration: 1. 7. 2020 - 30. 6. 2023
Program: APVV
Project leader: RNDr. Bučková Mária PhD.
Annotation:The microbial colored stains on historical papers (documents and books) are a worldwide problem, which may considerably vary due to regional climate and microbial diversity. It is necessary to develop a cost-effective technique facilitating effective yet gentle removal of the colored microbial stains from the surface of historical papers. The current knowledge indicates that some enzymes, belonging to peroxidase and laccase groups, have the ability to decolorize various kinds of dyes. Some of them are commercially available, while others can be extracted from a large range of microorganisms that produce them, mainly Basidiomycota. Therefore, it is possible to exploit this property in order to remove microbial pigments or colorants. For this purpose, we shall utilize enzymes as active components of tailored techniques to remove the stains without interfering with or destroying the fragile and precious paper of historical documents and books. In frames of the research project, in addition to production of enzymatic extracts and their application, several other aspects will be investigated, such as: isolation of pigment / color producing microorganisms responsible for the microbial stains on paper; selection of peroxidase /laccase producing microbial isolates; chemical composition of colored stains on real paper items and on model paper samples; development of a non-destructive strategy for identifying the stains directly from historical items. The gained knowledge and developed tools will immediately help Slovak restorers and conservators, which are involved in the project (Academy of Fine Arts and Design in Bratislava; partner of the project), and also other institutions as for example Slovak National Archives and the University Library in Bratislava. Moreover, the international cultural protectors will also benefit from the developed approaches.

FUNPOX - Hybrid, lignolytic and versatile heme peroxidases from Ascomycetes and Basidiomycetes

Hybridné, lignolytické a verzatilné hémové peroxidázy z askomycétnych a bazidiomycétnych húb

Duration: 1. 1. 2018 - 31. 12. 2021
Program: VEGA
Project leader: RNDr. Zámocký Marcel DrSc.

CTC - Identification and validation of signalling pathways associated with circulating tumor cells in breast cancer.

Identifikácia a validácia signálnych dráh asociovaných s cirkulujúcimi nádorovými bunkami pri karcinóme prsníka

Duration: 1. 7. 2017 - 30. 6. 2021
Program: APVV
Project leader: Mgr. Kľučár Ľuboš PhD.
Annotation:Circulating tumor cells (CTC) are indepent prognostic factor in primary as well as in metastatic breast cancer. CTC are heterogenous population of tumor cells and play crucial role in metastatic cascade and tumor progression in process termed self-seeding. Presence of CTC in peripheral blood is a surrogate marker of tumor metastatic ability. Identification of signalling pathways associated with presense of CTC in peripheral blood could help to identifify new therapeutic targets in breast cancer. This project is aimed to identify biomarkers and subsequently signalling pathways in primary tumor associated with different subsets of CTC using using highthroughput technologies of genomics and biostatistcs through translational research involving the analysis of biological material from patients followed by their prospective validation.

Isolation and advanced characterization of new probiotic microorganisms with potential for use in biomedicine and biotechnology

Izolácia a pokročilá charakterizácia nových probiotických mikroorganizmov s potenciálom pre uplatnenie v biomedicíne a biotechnológiách

Duration: 1. 1. 2018 - 31. 12. 2021
Program: VEGA
Project leader: RNDr. Pevala Vladimír PhD.
Annotation:Probiotic microorganisms are widely used in preventive and supportive biomedicine and in food biotechnology. The use of new probiotic strains in preclinical and clinical experiments and in practice requires comprehensive and detailed analysis of the strains at phenotypic, biochemical and molecular level. The proposed project aims at isolation and characterization of new probiotic strains of the Bifidobacteria and Lactobacillales taxons. We propose that these new isolated strains could have unique beneficial properties so they could be useful in biomedicine and biotechnology. Another objective of the project is to perform advanced study of the Lactobacillus plantarum LS/07, a strain with proven anti-inflammatory and anti-tumor effects. Goal of the project is to carry out genome and secreted proteome analysis using advanced molecular-biological techniques. This characterization of the strain is essential for assessing its safety for human use.

Combination of nanoparticles and essential oils for mitigating the biodeterioration on various types of building materials

Kombinácia nanočastíc a esenciálnych olejov na zmiernenie biologického poškodenia rôznych typov stavebných materiálov

Duration: 1. 1. 2019 - 31. 12. 2021
Program: VEGA
Project leader: RNDr. Bučková Mária PhD.
Annotation:The aim of the research is to gain a new knowledge about of the use of various combinations of nanoparticles and superhydrophobic particles with essential oils in order to inhibite the biodeterioration of traditional as and modern building materials. Antimicrobial effects of selected essential oils with nanoparticles and superhydrophobic particles on natural materials and modern building materials, such as wood (whitewood, pine, etc.), travertine, granite, sandstone, plastics and ceramics to reducing or completely suppressing microbiological damage will be evaluated. Nanoparticles and superhydrophobic particles (SHPs) should increase the antimicrobial effect of essential oils by formation of hydrophobic barrier and thereby inhibit the growth of microorganisms.

SafeCheese - Microbial contaminants in traditional Slovakian cheeses: their elimination by scientific tools based on quantitative analysis and mathematical modelling

Mikrobiálne kontaminanty v tradičných slovenských syroch: ich eliminácia vedeckými nástrojmi založenými na kvantitatívnej analýze a matematickom modelovaní

Duration: 1. 7. 2020 - 30. 6. 2023
Program: APVV
Project leader: Dr. Pangallo Domenico DrSc.
Annotation:The microbiological safety of traditional Slovak cheeses (“bryndza”, “oštiepok”, “parenica”, “korbáčiky”) has increased in recent years due to modifications in production technology and improved hygiene conditions. Nevertheless, in the case of the traditional method of production from unpasteurized ewe's milk, there is a continuing threat of enterobacteria and toxinogenic staphylococci, which are permanently present at relatively high levels in the initial raw material. In recent years, microorganisms capable of long-term persistence in a production environment, such as the dangerous pathogenic bacterium Listeria monocytogenes, have been associated with these microorganisms, which endanger the safety and quality of the products. Filamentous fungi have to be generally eliminated from eukaryotic microorganisms due to undesirable surface growth. Wild strains of Mucor circinelloides and Geotrichum candidum appear to be, due to their rapid growth, indicative in cheeses, despite their involvement in the maturing of lump cheeses. The aim of the project will be to characterize the growth and reproduction of these microorganisms in media, milk and cheese depending on conditions (temperature, pH, aw) using predictive microbiology and mathematical modelling procedures. Part of the research will be focused to definition of conditions for their reduction and elimination. The acquired knowledge will be a basis for increasing of microbiological safety and quality of traditional Slovakian cheeses.

Terafag - Bacteriophage preparations for therapy of vaginal and urinary infection

Príprava bakteriofágov na terapiu vaginálnych a močových infekcií

Duration: 1. 7. 2017 - 30. 6. 2021
Program: APVV
Project leader: RNDr. Bukovská Gabriela CSc.
Annotation:The increasing occurrence of antibiotic-resistant pathogens is a major problem in current health care.Bacteriophages are viruses capable to kill bacteria and therefore have a great potential to be used in the treatment of infectious diseases, especially in the case of resistant bacteria. The lack of knowledge about the phage biology previously often led to disappointing results. Therefore, a comprehensive study of the therapeutic phage properties is a prerequisite for their full application potential. In this project, we will isolate and characterize bacteriophages specific for selected bacterial pathogens which are causative agents of urinary tract infections or which potentially threaten newborns. We will prepare a phage cocktail which will be effective in eliminating of model pathogens.

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. Kormanec Ján DrSc.
Annotation:Bacteria of the genus Streptomyces are dominant producers of secondary metabolites with a wide range of biological activities. Genes for these metabolites are physically clustered. The aim of the project is the preparation and characterization of new antibiotics and antitumor agents by manipulation of secondary metabolite genes and synthetic biology methods. The project builds on the previous APVV project, where we determined the genomic sequence of our model strain S. lavendulae subsp. lavendulae CCM 3239, as well as its transcriptome in wild-type and mutant for the global regulator of secondary metabolism. In addition to the cluster for the unique antibiotic auricin, we have bioinformatically identified 30 gene clusters for potentially new secondary metabolites that are silent under laboratory conditions. The aim of the project will be to activate them by integrating strong promoters in front of genes for positive pathway-specific regulators or biosynthetic operons and charaterizing induced biologically active substances. The clusters will be cloned and integrated into the genome of the S. lividans RedStrep heterologous strain to genetically modify them to produce more potent biologically active agents. The structure of auricin and the organization of its gene cluster suggested a unique mechanism for its biosynthesis. The aim will be to characterize this biosynthesis and biological properties of prepared auricin intermediates. We previously successfully introduced the methodology of synthetic biology for the formation of new secondary metabolites. The aim will be to use this approach for characterization of auricin biosynthesis as well as for the production of new biologically active substances using a combination of genes for auricin and other polyketide antibiotics. Our results will contribute to the knowledge of secondary metabolite biosynthesis and may reveal new biologically active substances with efficient therapeutic properties.

PPIS - Regulation of Pericellular Proteolysis: From Molecular Mechanisms To Novel Immune Cell Subsets and Therapeutic tools

Regulácia pericelulárnej proteolýzy: od molekulárnych mechanizmov k novým subsetom imunitných buniek a terapeutickým nástrojom

Duration: 1. 7. 2017 - 30. 6. 2021
Program: APVV
Project leader: Mgr. Leksa Vladimír PhD.
Annotation:Plasminogen system is one of the major proteolytic pathways. It is harnessed in many physiological processes, particularly in immune responses. The overall objective of the project is to delineate novel molecular mechanisms that control plasminogen activation in both adaptive and innate immune responses, namely in T cell migration, cytokine activation and homeostasis maintenance by macrophages. The project stems not only from our published data but also from our recent unpublished discoveries and solid preliminary results. Specific goals of the project are not mutually exclusive; there is substantial integration not only at the level of underlying cellular and molecular mechanisms and targets, but also at the level of experimental approaches, tools and devices. The major deliverables of the project will not only include deeper understanding of molecular mechanisms underlying plasminogen activation and characterization of immune cells employing these mechanisms, namely subsets of T cells and macrophages; but also novel molecular tools to pharmacologically modulate the imbalanced plasminogen activation which is associated with many human pathologies, such as chronic inflammatory diseases or cancer. The project achievements will be definitely of interest for scientists in basic research, but also for medical doctors and pharmacological companies.

Signal cascades of regulation of sigma factors of RNA polymerase in response to stress, cell and physiological differentiation in soil bacteria of the genus Streptomyces

Signálne kaskády regulácie sigma faktorov RNA polymerázy pri odozve na stres, bunkovej a fyziologickej diferenciácii u pôdnych baktérií rodu Streptomyces

Duration: 1. 1. 2020 - 31. 12. 2023
Program: VEGA
Project leader: RNDr. Kormanec Ján DrSc.
Annotation:In natural environment, bacteria are exposed to various stresses. Response to these stresses is mainly mediated by stress-response sigma factors of RNA polymerase. The Streptomyces coelicolor genome encodes up to 9 homologues of these sigma factors and a large number of their regulators (anti-sigma factors, anti-anti-sigma factors and signal PP2C phosphatases). Previously, we have characterized the role of these sigma factors, demonstrated their dual role in stress and differentiation, as well as their regulatory interconnection. Using several approaches, we have demonstrated interactions between all sigma factors, anti-sigma factors and anti-anti-sigma factors, as well as the phosphorylation of anti-anti-sigma factors with multiple anti-sigma factors, suggesting a complex regulation. The aim of this project is to further characterize these sigma factors, their complex regulation and their activation in response to a specific stress or differentiation signal through signal activating PP2C phosphatases.

Assembly of Septin Complex to Higher Order Structures.

Skladanie septínového komplexu do štruktúr vyššieho poriadku.

Duration: 1. 1. 2019 - 31. 12. 2022
Program: VEGA
Project leader: RNDr. Farkašovský Marian CSc.
Annotation:Septins are conserved guanosine phosphate–binding proteins involved in cytokinesis and other essential membrane remodeling functions. These ubiquitous proteins form heterooligomeric complexes, which polymerize into nonpolar filaments. The mechanisms of formation a localization of septin higher order structures and the regulation of septin ring assembly are difficult to study and therefore poorly understood. Our main goal is to explain how the protein kinases as well as septin sumoylation are involved in the regulation of coordinated assembly of septins in different stages of the cell cycle. We will study the in vitro phosphorylation and sumoylation of GFP-labelled septins by fluorescence microscopy observing the formation of kinase reaction and sumoylation products in free solution and on lipid bilayer. Cryo-electron microscopy will be employed to obtain structural details. Observation of the localization and structural changes of the septin cortex in vivo will support our in vitro findings.

The study of model bacteriophages’ replication proteins in system bacteriophage - host

Štúdium replikačných proteínov modelových bakteriofágov v systéme bakteriofág – hostiteľ

Duration: 1. 1. 2018 - 31. 12. 2021
Program: VEGA
Project leader: RNDr. Bukovská Gabriela CSc.
Annotation:Bacteriophages are characterized by a unique genome and an individual structure of proteins, in particular replication. Our main goal is elucidation of replisome composition of orynephage BFK20 and bacteriophage phiBP within the process of phage DNA replication in their host bacteria Brevibacterium flavum and Paenibacillus polymyxa. In the solution of the project we will focus on characterization of selected phage and bacterial replication proteins. We intend to study structure of proteins, to characterize the catalytic domains and to confirm the phage replication protein activities. The expected result will be understanding the replication mechanism of phage BFK20. Our results achieved by solving of the project will be a contribution to the understanding of bacteriophage replication mechanism with new information about the phage and bacterial replication proteins.

Study of the effect of cardiac arrhythmia-associated mutations on the structure and function of the human ryanodine receptor 2

Štúdium vplyvu mutácií asociovaných so srdcovými arytmiami na štruktúru a funkciu ľudského ryanodínového receptora 2

Duration: 1. 1. 2020 - 31. 12. 2023
Program: VEGA
Project leader: Mgr. Bauerová Vladena PhD.
Annotation:The human ryanodine receptor 2 (hRyR2) is a calcium channel whose main function is to release calcium ions from the sarcoplasmic reticulum into the cytoplasm, making it responsible for regular heart function. More than 300 mutations have been identified in the gene of this protein which affect its function, thereby causing a number of diseases (ARVD/C2, CPVT1, SUO, SCD, SID). These lead to heart failure and, in many cases, human death. Most pathological mutations in the RYR2 gene appear in three clusters, one each in the N-terminal, central and C-terminal regions. The main aim of this project is to study selected mutations associated with heart arrhythmias using in vitro and in silico approaches. The project will significantly contribute to the characterization of selected mutations at the biochemical, biophysical and structural levels and will help to understand the channel opening/closing processes in the above-mentioned pathological conditions.

Effect of honeybee glucose oxidase on honey antibacterial properties and characterisation its production and activity in hypopharyngeal glands of honeybee (Apis mellifera)

Vplyv včelieho enzýmu glukózooxidáza na antibakteriálne vlastnosti medu a charakterizácia jeho produkcie a aktivity v podhltanových žľazách včely medonosnej (Apis mellifera)

Duration: 1. 1. 2018 - 31. 12. 2021
Program: VEGA
Project leader: Ing. Majtán Juraj DrSc.

Vannote - Research & development of effective processes for the preparation of vanillin and other natural flavors using the oxidative and protective effect of recomtinant catalase and peroxidase

Výskum a vývoj efektívnych procesov prípravy vanilínu a iných prírodných aróm s využitím oxidačného a protektívneho účinku rekombinantnej katalázy a peroxidázy

Duration: 1. 8. 2018 - 30. 6. 2022
Program: APVV
Project leader: RNDr. Zámocký Marcel DrSc.

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: Mgr. Kľučár Ľuboš 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.

Interaction between proteases, chaperones and kinases in stress condition cause by pathological conditions.

Vzájomná inerakcia proteáz, šaperónov a kináz v mitochodriách pri strese spôsobenom patologickými stavmi.

Duration: 1. 7. 2020 - 30. 6. 2024
Program: APVV
Project leader: Ing. Kutejová Eva DrSc.

IMcheck - Assessing immune-checkpoints in B cell malignancies

Zhodnotenie imunitných kontrolných bodov u B bunkových malignít

Duration: 1. 7. 2017 - 30. 6. 2021
Program: APVV
Project leader: Mgr. Kľučár Ľuboš PhD.
Annotation:Cancer immunotherapy is the idea of boosting the tumor-specific adaptive immune activities instead of directly targeting cancer cells. However, cancer cells can avoid immune surveillance by suppressing immunity through activation of specific inhibitory signaling pathways, referred to as immune checkpoints. Recently, the blockade of checkpoint molecules such as PD-1, PD-L1 and CTLA-4, with monoclonal antibodies targeting these checkpoint molecules has enabled the development of breakthrough therapies in oncology, with ongoing preclinical and clinical trial in B-cell malignancies. The overall objective of this proposal is study of B cell malignancies focusing on immune checkpoints molecules evolve either in clonal tumor or immune accessory populations of tumor microenvironment. Moreover, we will evaluate blockade effect of immune checkpoints neutralizing antibodies either alone or in combination together (or with novel immunomodulatory drugs) to increase their efficacy as potential therapy for patients with B-cell malignancy. Therefore, characterizing blockage effect of immune checkpoint inhibitors, either alone or in combination, on tumor cells within the tumor microenvironment will help to better understand lymphomagenesis providing the framework of development of new immune-based therapeutic strategies.

Projects total: 23