Thrombo-inflammation is a complex process which involves players of innate as well as adaptive immunity to participate in close coordination with the coagulation system to mediate inflammation-associated cellular dysfunction. Disease promoting stimuli such as hyperglycemia, genetic risk factors, or thrombophilia trigger inter-cellular cross-talk via cellular and extra-cellular mediators. Coagulation regulators expressed by a wide variety of cells such as endothelial cells, trophoblast cells, immune cells or tissue-resident cells regulate this cross-talk and therefore thrombo-inflammation. Platelets, popularly known for their role in maintaining hemostasis, are increasingly recognized as key regulators of vascular inflammation. Cell-derived extracellular vesicles (EVs) mediate intercellular communication through cargos composed of proteins, lipids, and nucleic acids.
The exact composition of EVs depends on type and state of the originating cell. These cellular cargos can also be present in an unpackaged form (such as cell-free circulating DNA, cfDNA) and mediate the cellular cross talk. Following activation by a wide variety of agonists, platelets and other cell types release a wide range of biologically active substances and EVs. While platelets and EVs are physiologically required during development, they are also involved in vascular complications, such as in pregnancy or renal vascular diseases.
The focus of our research group is to better understand the contributions of these mediators of thrombo-inflammation in such physiological (development) and pathological conditions and establish targeted therapies. Current projects in our group aim at studying the role of platelets and EVs in thrombo-inflammation. We are also interested in elucidating changes in EV composition during inflammation and its functional impact on vascular inflammation. Furthermore, we aim at dissecting the role of platelets and associated coagulation regulators in pregnancy, renal development and vascular complications at the glomerular filtration barrier.
We are employing several mouse models and state of the art techniques such as microfluidics, digital droplet PCR, exosome purification, nanoparticle tracking analysis and unbiased approaches including LC-MS/MS (cooperation: Prof. Ceglarek) and single-cell RNA-seq. Studying the role of thrombo-inflammatory mediators in vascular complications will lay the ground for the identification of new biomarkers and potential therapies.
