CRU 274: Platelets - Molecular Mechanisms and Translational Implications

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).

Platelets play a critical role in thrombosis and bleeding. Beyond cardiovascular diseases such as myocardial infarction, deep vein thrombosis, pulmonary embolism or stroke, platelets are central players in the pathophysiology of thromboinflammation which outstretches towards a variety of diseases including sepsis, pathogen-related infections, angiogenesis, and tumor metastasis or organ regeneration. Most of elder patients are treated with antithrombotics for disease control. Thus, a deep understanding of the molecular mechanisms of platelets in disease development and its translational implications for clinical medicine is an important scientific and rapidly expanding field. The aim of the Clinical Research Unit (CRU-274) “Platelets-Molecular Mechanisms and Translational Implications” was i) to elaborate basic molecular mechanisms of platelet (patho-) physiology with a strong disease relevance, ii) to establish a disease- and patient-oriented research consortium that concentrates on platelets to establish and to improve translational medicine, iii) to foster clinical and scientific structures and profiling of the Medical Faculty of Tübingen, iv) to create effective training structures to promote young scientist especially with clinical background, v) to interlink and to improve basic science with clinical research and to foster translational medicine and vi) to increase the scientific international visibility of our research. The funding and research activity of the CRU-274 was the basis for the establishment of the Transregio-SFB consortium between the Universities of Tübingen and of Würzburg which started in 2018. Thus, the promotion of the CRU-274 was successful to establish strong research structures, a prerequisite to foster the research activity in this highly expanding field relevant for clinical medicine. This support has made a significant impact on profiling of the research priorities of the University of Tübingen and has helped us to achieve a high international visibility in this expanding research field. Aim of the clinical research unit was to study the importance of the integrative functions of platelets for processes such as thrombosis and hemostasis, inflammation, angiogenesis, apoptosis or innate immunity and to define their consequences for disease development using disease models in mice and clinical studies. The clinical research unit focused on disease and patient-oriented issues in an interdisciplinary research network. By connecting basic science with clinically relevant disease models and human studies, the CRU-274 focused on improving medical care and offered a high degree of translational perspectives. In addition to developing a deeper understanding of the disease, the clinical research unit was concentrating on the development of innovative research methods (e.g. genetic mouse models for in vivo imaging, "single cell imaging") and on new diagnostic and therapeutic approaches, some have already been translated into clinical trials (e.g. biomarkers, molecular imaging, antithrombotic therapy in patients at risk of bleeding, clinical studies of phase I and II). Furthermore, the research unit bundled a system approach of platelet "proteomics /-lipidomics /-metabolomics” to enable a more targeted use of medical treatments (individualized medicine). During the funding period, a variety of research disciplines were involved including cardiology, physiology, biochemistry, structural biology, pharmacology, physics, cell biology, imaging, bioinformatics, or medical chemistry. Thus, the CRU-274 has integrated successfully basic scientists and clinical researchers within a highly motivated and creative consortium.