Lab Location: Anna Spiegel Center of Translational Research, Level 5
Associated Clinical Departments: General Surgery, Vascular Surgery
Phone: +43-1-40400-73514, -73524
C. Brostjan has a prime interest in vascular biology and disease, addressing the interplay of endothelial cells, platelets and leukocytes in pro-inflammatory activation, coagulation and angiogenesis. While the focus was previously placed on tumor endothelium and anti-angiogenic cancer therapy, the research interests have evolved to the field of thrombosis and abdominal aortic aneurysms. The projects include basic research on gene and protein regulation initiated by the interaction of endothelial cells and blood cell populations. Furthermore, translational studies with blood and tissue analyses are focused on patients with abdominal aortic aneurysm.
1. Thrombospondin-1 (TSP-1) isoforms in hemostasis and thrombosis
Blood clotting is supported by the platelet factor TSP-1. Inflammatory cells such as neutrophilic leukocytes can process thrombospondin-1 to a smaller protein variant. This project is conducted in the context of a research consortium (FWF SFB-54) and is designed to determine whether proteolytic processing of TSP-1 is a mechanism by which inflammatory reactions can alter the function of TSP-1 thereby promoting blood clotting and the tendency for thrombotic events.
2. Neutrophils and extracellular traps in abdominal aortic aneurysms
The abdominal aortic aneurysm (AAA) develops upon media destruction by proteolytic matrix degradation and apoptotic death of smooth muscle cells. Neutrophils are known to accumulate in the vessel wall and intraluminal thrombus of AAAs and to contribute to aortic degeneration by the release of proteases, reactive oxygen species and by formation of neutrophil extracellular traps (NETs). The project evaluates the marker value of neutrophil activation and NET parameters in blood and tissue of AAA patients for their diagnostic and prognostic potential (prediction of rapid progression or rupture). Furthermore, distinct types of NETs based on nuclear or mitochondrial DNA are investigated and their therapeutic potential is assessed in mouse studies.
3. Monocyte subsets in cancer
Monocytes represent a heterogeneous population with subsets of distinct phenotype and function. While we have previously found that the so-called “intermediate monocytes” (known to be associated with angiogenesis and tissue remodeling) are elevated in colorectal cancer patients and their rise predicts response to chemotherapy, the current investigations are focused on monocyte subsets in endocrine breast cancer therapy.