Our research focuses on the mechanisms of thrombo-inflammation and the interaction between platelets and immune cells in various diseases such as stroke or liver inflammation. To do so we capitalize on advanced fluorescence microscopy techniques and transgenic mouse models to study the role of platelets in inflammatory processes.
The term thrombo-inflammation was used first to describe the interplay of components of the thrombotic and inflammatory system driving ischemia/reperfusion (I/R) injury in acute ischemic stroke. Today, thrombo-inflammation is recognized as a major pathomechanism in a continuously growing number of disorders in different organs and disease states. Despite platelets being critically involved, the classical thrombosis is not the major pathophysiological event leading to organ damage, which discriminates thrombo-inflammation from immunothrombosis.
For many thrombo-inflammatory diseases the underlying mechanisms are largely unknown and therapeutic options are limited. To develop novel treatment strategies, it is necessary to understand the detrimental interplay between thrombotic and inflammatory circuits, which would only be possible if the cellular interactions can be visualized. To image thrombo-inflammatory processes and their consequences with different advanced imaging modalities, we collaborate intensively with the Bio-Imaging Center. By developing new tools and protocols for visualizing platelets and their precursor cells, megakaryocytes (MKs), using multiphoton intra-vital microscopy (2P-IVM) and light-sheet fluorescence microscopy, we have challenged previous concepts of MK maturation and clarified their interaction with neutrophils in the bone marrow. With the established techniques we currently aim to study and visualize alterations in the bone marrow upon thrombo-inflammation in the context of myocardial infarction. So far, our findings provided new insights into the pathomechanisms underlying ischaemic stroke and identify key factors involved in infarct progression, such as the neuronal capacitive calcium channel Orai2, platelet degranulation, and the platelet receptor CD84. Additionally, we have discovered a CLEC-2/αIIbβ3-dependent platelet activation pathway as a powerful trigger of cerebral venous thrombosis (CVT) in mice, offering the first direct evidence for aberrant platelet activation as a major trigger of CVT and a potential target for treatment.