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Cost International Projects National Projects Bilateral Scientific Cooperation Национални пројекти HORIZON-RIA ИДЕЈЕ позив Proof of Concept Доказ концепта

Determination of the Mutational Landscape and Clonal Architecture and Their Application in Angiogenesis and Thrombosis in Patients with MPN

Project leader: Dr. Radek Skoda, Dr. Vladan Čokić

Project collaborators: Dr. Dragana Marković

Project number: IZ73Z0_152420/1

Duration of the project: 2014-2016.

Leading institution: Department of Biomedicine, University of Basel and University Hospital Basel, Switzerland

Description of the project:

Тип пројекта:

International Projects

Converting Molecular Profiles of Myeloid Cells into Biomarkers for Inflammation and Cancer

Project leader: Dr. Sven Brandau

Project collaborators: Dr. Juan Santibañez, Dr. Slavko Mojsilović, Dr. Milica Vukotić

Project number: CA20117

Duration of the project: 2021-2025.

Leading institution: University Hospital Essen, Essen, Germany

Description of the project:

Myeloid immune cells are important mediators in the pathology of many diseases, especially in diseases associated with chronic inflammation (DACI). Recent advancements in molecular profiling technologies have led to the generation of large data sets, many of those not fully explored yet, but accessible to the entire scientific community via public data repositories. It is the aim of this COST Action to repurpose those data sets, retrieve and curate myeloid cell-specific information, and apply this information to develop novel biomarkers for DACI. To this end, Mye-InfoBank utilise COST networking tools to enable the interaction of molecular biologists, bioinformaticians, immunobiologists, biobank coordinators and clinicians. The concerted activity of these experts on myeloid cell biology (either basic or clinical research), bioinformatics, and bio-banking, will transform complex molecular information into standardised and applicable biomarkers, which have the potential to improve clinical decision making in a number of socio-economically important diseases.

Тип пројекта:

Cost

European Network of Investigators Triggering Exploratory Research on Myeloid Regulatory Cells

Project leader: Dr. Sven Brandau

Project collaborators: Dr. Juan Santibañez, Dr. Vladan Čokić, Dr. Slavko Mojsilović, Dr. Jelena Krstić, Dr. Sunčica Bjelica

Project number: BM1404

Duration of the project: 2014-2018.

Leading institution: University Hospital Essen, Essen, Germany

Description of the project:

This Action formed a network of researchers and clinicians with the aim to establish a gold standard of common protocols and harmonize guidelines for the analysis and clinical monitoring of myeloid regulatory cells (MRCs). There is also a deficit in the translation of findings from animal models to humans, and Mye-EUNITER built an analytical mouse-monkey-man correlation line. Standardized and validated tools for MRC analysis aid the development of cellular biomarkers of disease and guide the design of novel therapies to manipulate the functions of MRCs. Members of the Action from IMR actively engaged in the activities of working groups through attending meetings, workshops, short-term scientific missions, and writing papers.

Тип пројекта:

Cost

Etiology and Prevention of Thrombosis in Hematologic Malignancies

Project leader: Dr. Olivera Mitrović Ajtić

Project collaborators: Dr. Vladan Čokić, Dr. Dragoslava Đikić, Dr. Teodora Dragojević, Dr. Tijana Subotički, Dr. Milica Vukotić

Project number: 7749695

Duration of the project: 20.01.2022-20.01.2025.

Leading institution: Institute for Medical Research, University of Belgrade

Description of the project:

In order to discover the mechanism underlying frequent thrombosis in hematologic malignancies, it will be initiated the inflammation dependent activation and interplay of endothelial cells, platelets, and leukocytes with subsequent formation of microparticles and nitric oxide (NO) linked to thrombus generation by induction of coagulation and fibrinolysis. Cancer-associated thrombosis (CAT) is the second leading cause of death in cancer patients including both venous and arterial thromboembolism. While CAT can be treated with anticoagulants, benefits of therapy must be balanced with the increased bleeding risks. The coagulation related cells and biomarkers will be analyzed and selected by flow cytometry from the following hematologic malignancies: multiple myeloma, lymphoma, acute myeloid leukemia, and transplanted patients with graft-versus-host disease (GvHD). Besides clinical follow-up of the patients, extensive preclinical studies will be performed using in vitro cell cultures (hypoxia chamber, RT-qPCR, immunoassays), in vivo mouse models (NO analyzer), and in silico profiling. Activation of the coagulation factors will be observed through the prothrombotic properties of endothelium (microchip flow-chamber system), neutrophil extracellular traps (NETs, spectrophotometry) and anticancer treatments. The proposed study will show inflammatory stimulation of hypercoagulability, chemotaxis of immune response, and NET formation as well as modulation of fibrinolytic system and miRNA regulated platelet activation. In addition, the equilibrium between NO production and oxygen tension will largely influence the inflammation-dependent thrombus formation, with a prognostic significance of hypoxia related gene signature. Understanding the principal mechanisms may allow the development of new therapies to safely prevent CAT in the hematologic malignancies and GvHD, while determination of the specific biomarkers in each malignancy can be used as predictors of thrombosis.

Тип пројекта:

National Projects

Androgen-Dependent SARS-CoV-2 Stimulation of the Hyperinflammatory Response in COVID-19

Project leader: Dr. Vladan Čokić

Project collaborators: Dr. Juan Santibanez, Dr. Olivera Mitrović Ajtić, Dr. Milica Vukotić, Dr. Dragoslava Đikić, Dr. Tijana Subotički, Dr. Teodora Dragojević

Project number: 7547934

Duration of the project: 2021-2022.

Leading institution: Institute for Medical Research, University of Belgrade

Description of the project:

Severe acute coronavirus virus syndrome 2 (SARS-CoV-2)-induced hyperinflammation is a major reason for severe clinical outcome of coronavirus disease 19 (COVID-19), principally in male patients. Cell entry of SARS-CoV-2 depends on binding to angiotensin-converting enzyme 2 (ACE2) and androgen-regulated transmembrane serine protease 2 (TMPRSS2). We propose a novel androgen-dependent mechanism of ACE2 activation by SARS-CoV-2 in endothelial and immune cells; as well as endothelial dysfunction and hyperinflammation stimulated immune response predispose to thrombus formation in COVID-19. SARS-CoV-2 will be isolated, in vitro expanded, and used to monitor cell signaling and cytokine storm by immune assays and viral load by RT-qPCR. Related androgen pathways will be pharmacologically targeted. Immune-endothelial cell co-cultures will be performed for thrombosis development. We expect androgen-dependent SARS-CoV-2 host cell infection and mediated inflammation in thrombotic complications. This translational research will reveal androgen pathways implication in SARS-CoV-2 infection and therapeutic strategies to speed up patient recovery.

Тип пројекта:

National Projects

The Pathogenetic Mechanisms in Hematological Malignancies

Project leader: Dr. Vladan Čokić

Project collaborators: Dr. Dragana Marković, Dr. Marijana Kovačić

Project number: ОI175053

Duration of the project: 2011-2019.

Leading institution: Institute for Medical Research, University of Belgrade

Description of the project:

Тип пројекта:

National Projects

Hydroxyurea-Mediated Activation of Nitric Oxide Synthase in Erythroid Progenitors

Project leader: Dr. Milica Vukotić

Project collaborators: Dr. Teodora Dragojević, Dr. Tijana Subotički, Dr. Miloš Diklić, Dr. Olivera Mitrović Ajtić, Dr. Vladan Čokić

Project number: 6061921

Duration of the project: 2020-2022.

Leading institution: Institute for Medical Research, University of Belgrade

Description of the project:

The aim of this project is to investigate potential involvement of NOS enzymes in the molecular mechanism of action of the chemotherapeutic agent hydroxyurea, which is used for the treatment of myeloproliferative neoplasms, chronic myeloid leukemia, and solid tumors. Obtained results should answer the following scientific questions: 1) if HU activates NOS enzymes via direct interaction or indirectly, 2) if inhibition or reduced protein expression of NOS enzymes at least partially rescues HU-induced proliferation block and apoptosis and, 3) which of the NOS isoforms is involved in these processes? Primary mouse erythroid cells isolated from bone marrow and human erythroleukemic cell lines will be used in this study. The relevance of the results obtained in vitro will be confirmed by in vivo treatment of Nos2- or Nos3- deficient mice. Comprehensive knowledge of the molecular mechanism of HU might help improve its beneficial properties and decrease adverse effects.

Тип пројекта:

National Projects