TRR 23:  Vascular Differentiation and Remodelling

• Subject Area: Medicine ; Biology
• Term: from 2005 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5486332

Vascular disease directly or indirectly accounts for approximately 70 percent of human deaths and is intimately linked with a number of conditions such as stroke, myocardial infarction, peripheral artery disease, hypertension, rheumathoid arthritis, and cancer as well as the new epidemics of diabetes and obesity. Despite the high social and economical impact of vascular disease, surprisingly little is known about the molecular and cellular mechanisms that affect the cells of the vessel wall during disease development.
Moreover, the functional analysis of the molecular mechanisms that regulate blood vessel formation has in the past concentrated on the characterisation of pro- and anti-angiogenic molecules that directly act on endothelial cells. This preoccupation with the function of isolated endothelial cells implies that interactions between endothelial cells and other vascular cells, such as pericytes and smooth muscle cells as well as the role of vascular progenitor cells, are not well understood.
The Transregional Collaborative Research Centre is studying the vessel wall in health and disease using a variety of state-of-the-art methods, including molecular and cellular biology, vascular physiology, transgenic mice and in-vivo-imaging technology. The work programme is divided into three sections. Project area A summarises the projects that concentrate on the role of mediators and effectors that act on vascular cells. Project area B deals with cellular responses to exogenous stimuli, whereas project area C includes projects centered on cellular and systemic interactions between vascular cells and investigates complex regulatory mechanisms in vivo. One basic concept links all of the projects, namely the notion that the vessel wall is a highly organised multicellular system that requires the interdisciplinary analysis of all of the major cell types involved.

• DFG Programme: CRC/Transregios

Completed projects

• A01 - Characterization of BMPER, an endothelial precursor cell derived BMP regulator in vascular differentiation and remodeling (Project Head Moser, Martin )
• A02 - Role of integrin activity regulation for endothelial cell adhesion, migration and angiogenesis (Project Heads Chavakis, Emmanouil ;  Dimmeler, Stefanie )
• A03 - Role of the Angiopoietin/Tie system in controlling vascular morphogenesis and homeostasis (Project Head Augustin, Hellmut G. )
• A04 - Regulation of vascular Notch signalling by EGFL7 (Project Head Schmidt, Mirko H.H. )
• A05 - Function of podoplanin in lymphangiogenesis (Project Head Schacht, Vivien )
• A06 - The Cytochrome P450/soluble epoxide hydrolase axis in angiogenic endothelial cell signalling and vascular differentiation (Project Head Fleming, Ph.D., Ingrid )
• A07 - The role of Notch ligands during blood vessel development (Project Head Fischer, Andreas )
• A08 - Physiological roles of collagen-binding integrins on endothelial cells in angiogenic sprouting and vessel integrity (Project Head Eble, Johannes Andreas )
• A09 - Mechanism controlling the transition from quiescent to activated endothelium by exocytosis of Wiebel-Palade bodies triggered by tumor cells (Project Head Schneider, Stefan Werner )
• A10 - Role of flow-induced microRNAs in vessel maturation (Project Head Dimmeler, Stefanie )
• B01 - Synopsis - Liver-specific vascular differentiation and functions (Project Heads Goerdt, Sergij ;  Géraud, Cyrill )
• B02 - Role of Junb and Junb target genes in vascular morphogenesis and homeostasis (Project Heads Angel, Peter ;  Schorpp-Kistner, Marina )
• B05 - Role of histone deacetylases (HDACs) for angiogenesis signaling in endothelial cells (Project Head Urbich, Carmen )
• B06 - Characterization of Nucleoside Diphosphate Kinase B as Novel Regulator of Angiogenesis (Project Heads Lutz, Susanne ;  Wieland, Ph.D., Thomas )
• B07 - Molecular analysis of the Wnt/ß-catenin pathway in endothelial differentiation and remodeling (Project Heads Liebner, Ph.D., Stefan ;  Plate, Karlheinz )
• C01 - Role of Angiopoietins in brain vascular homeostasis (Project Heads Plate, Karlheinz ;  Reiss, Yvonne )
• C02 - Analysis of the multistep nature of homing and incorporation of circulating progenitor cells during tumor angiogenesis (Project Heads Klüter, Harald ;  Vajkoczy, Peter )
• C03 - Impact of Rho GTPase expression on tumor neovascularization (Project Heads Gille, Jens ;  Henschler, Reinhard )
• C04 - Role of bone marrow derived progenitor cells to tumor vascularization: mechanisms and functional implications (Project Heads Machein, Marcia ;  Plate, Karlheinz )
• C05 - Regulation of the smooth muscle cell phenotype switch during remodeling processes of arteries and veins (Project Head Korff, Thomas )
• C06 - Endothelial cell-platelet-leukocyte interactions during vascular remodeling (Project Head Hecker, Ph.D., Markus )
• C07 - Mechanisms regulating vascular smooth muscle cell differentiation (Project Heads Offermanns, Stefan ;  Wettschureck, Nina )
• C08 - Role of the Meis2 homeobox transcription factor in endocardial cell differentiation and function (Project Head Stainier, Ph.D., Didier Y. )
• MGKZ03 - Integrated Research Training Group "Vascular Cell Biology" (Project Head Hecker, Ph.D., Markus )
• Z01 - Non-invasive assessment of tissue micro-morphology, vessel function and cell migration in vivo with contrast-enhanced MRI, VCT and hybrid imaging (Project Heads Bäuerle, Tobias ;  Kiessling, Fabian ;  Komljenovic, Dorde ;  Müller, Margareta M. )
• Z02 - Central tasks (Project Head Augustin, Hellmut G. )
• Z05 - The zebrafish as a model organism to study vascular differentiation and remodelling (Project Head Kroll, Jens )

• Applicant Institution: Ruprecht-Karls-Universität Heidelberg
• Co-Applicant Institution: Goethe-Universität Frankfurt am Main
• Participating Institution: Deutsches Krebsforschungszentrum (DKFZ); Max-Planck-Institut für Herz- und Lungenforschung; W.G. Kerkhoff-Institut
• Spokespersons: Professor Dr. Hellmut G. Augustin, since 7/2009; Professor Dr. Karlheinz Plate, until 6/2009