|Vascular network remodeling and the formation of new blood vessels (angiogenesis and arteriogenesis) plays an important role in the pathophysiology of ischemic cardiovascular disease, diabetes, hypertension, and cancer, which are the most common causes of mortality in western society. In the pediatric setting, improper vascular network remodeling during embryogenesis is a major cause of birth defects, and programs for cardiovascular disease in the adult. Formation of vascular and neuronal networks shows many similarities including common molecular cues and the principle of directed guidance. Factors originally reported to act as guidance factor in the nervous system, also mediate angiogenic remodeling events, and angiogenic factors like VEGF, affect neurogenesis. Furthermore, the patterning of blood vessels and nerves is interdependent, involving signals provided by nerves.||
Our goal is to generate novel genetic insights in the regulation of vascular development and arterial-venous vessel identity that can translate into therapeutic strategies. Our research projects aim at understanding the molecular regulation of angiogenesis and arteriogenesis.
We focus on four crucial aspects:
1) Formation of angiogenic sprouts and guidance of vessel sprouts by endothelial tip cells (Nature 2004, Development 2011; Circulation Research, 2012)
2) Imprinting of arterial-venous venous vessel identity by neural guidance genes and hemodynamic factors (Development 2004; Development 2012).
3) Formation, recruitment and growth of (native) arterial collateral networks in ischemic cardiovascular diseases (Circulation Research 2011; Development 2013)
4) Identification of evolutionary conserved principles of vascular and neuronal differentiation and patterning
For this purpose we characterize the mechanisms of vascular and neuronal development in experimental models including (transgenic) zebrafish, chick and mouse embryo. In addition, the concepts emerging from understanding the basic molecular principles governing vascular growth are translated into relevant pathologic settings including cerebral and cardiac ischemia models, and cancer. We specifically address arterial collateral development upon arterial occlusion and prevention-recovery from target organ damage (heart infarct, stroke).
Translational Medicine, from bench to bedside
Translation and integration of basic science concepts into clinical practice requires a continuous feedback from clinical specialists. We therefore have extensive collaborations with clinicians at the working in the field of cardiology and neurology. Our lab also contributes to the German Center for Cardiovascular Research (DZHK).
Key-words summarizing our work
angiogenesis, arteriogenesis, tip cell differentiation, vessel guidance, hemodynamics, tissue morphogenesis, neural guidance genes, neuro-vascular interface