KFO 274:  Platelets - Molecular Mechanisms and Translational Implications

• Subject Area: Medicine
• Term: from 2011 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 190538538

Platelets play an important role for haemostasis and thrombosis. Disturbed platelet function causes or aggravates diseases such as myocardial infarction, stroke, atherosclerosis and venous thromboembolisms. Platelet-related diseases represent a major reason and indication for patient admission and treatment, and its incidence is increasing. In recent years, associations of platelets with wound healing, immune defense, inflammation, angiogenesis, tumor progression/ metastasis and regeneration of the diseased tissue have been proposed. Platelets accumulate at site of vascular and tissue injuey and interact with a variety of surrounding target cells. Central cell functions in close proximity are influenced by platelets through direct interactions via specific adhesion receptors or by release of inflammatory mediators (microenvironment). Consequently, platelets bring together cellular and humoral factors at the site of tissue/ vascular injury, channel central aspects of cell function and thereby regulate processe of tissue regeneration and restoration of organ function. Through interaction with cellular and soluble factors, platelets constitute a central point of intersection (thrombocytosome) relevant for a variety of diseases. Platelet research has developed dynamically in recent years concerning clinical as well as basic research. Accordingly, our improved pathophysiological insights enabled us to design new diagnostic and therapeutic approaches, particularly for cardiovascular diseases (translational aspect). Nowadays, many patients benefit from application of new diagnostic tools together with the aid of specific anti-platelet drugs. The aim of the Clinical Research Unit "Platelets - molecular mechanisms and translational implications" is to gain profound insights into integrative mechanisms, how platelets tailor processes of thrombosis/haemostasis, inflammation, angiogenesis, apoptosis or immune defense ("innate immunity") and resulting implications for disease using disease models from cell to mouse to patients. The Clinical Research Unit is focused on disease- and patienten-relevant hypotheses within a interdisciplinary research association. Providing a close cooperation between basic research and clinically relevant studies with patients the Clinical Research Unit in conjunction with our existing structures ("Tübingen Platelet Investigative Consortium, TuePIC") concentrates on the improvement of health care and offers a high degree of translational perspective to facilitate a targeted application of medical treatment (individualized medicine).

• DFG Programme: Clinical Research Units

Projects

• Bedeutung GTPase-aktivierender Proteine (GAPs) mit BAR-Domäne für die Thrombozytenfunktion (Applicant Elvers, Margitta )
• Coordination - management - training - public relations (Applicant Langer, Harald )
• Identification of genetic and epigenetic biomarkers for platalet function and platelet-dependent inflammatory processes in an established prospective patients´ cohort (Applicants Geisler, Tobias ;  Schwab, Matthias )
• Influence of the platelet-derived DAMP HMGB1 on thrombosis and inflammation (Applicant Gawaz, Meinrad Paul )
• Interaction of platelet-derived inflammatory mediators and their receptors CXCR4 and CXCR7 regulating platelet function and inflammation (Applicant Gawaz, Meinrad Paul )
• Non-invasive molecular and morphological imaging of platelets and platelet targets (Applicants Feil, Robert ;  Pichler, Bernd ;  Schäffer, Tilman )
• PI3 kinase dependent regulation of ion channels and carriers in platelets (Applicant Borst, Oliver )
• Real-time analysis of cGMP signals in platelets in vitro and in vivo (Applicant Feil, Robert )
• Role of cyclophilins and other EMMPRIN-ligands for platelet function and platelet-monocyte interaction (Applicant Seizer, Peter )
• Role of platelets for tissue remodelling - modulation of angiogenesis, inflammation and apoptosis (Applicant Langer, Harald )
• Structure and function of "junctional adhesion molecules" (JAMs) expressed on platelets - characterisation of novel heterophilic interactions (Applicants Langer, Harald ;  Stehle, Thilo )

• Leader: Professor Dr. Harald Langer
• Spokesperson: Professor Dr. Meinrad Paul Gawaz