Ruprecht-Karls-Universität Heidelberg
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Geraud0119 - Scientist (f/m) / PhD position
Project no:
Geraud0119

Project leader:

Project supervisor:
Géraud, Cyrill
Application deadline:
31. Mar 2019
Start of PhD project:
1. Apr 2019

Project description:

Title:
Hepatovascular control of disease susceptibility and resistance via circulating blood factors
Summary:
Liver sinusoidal endothelial cells (LSEC) are unique organ-specific endothelial cells that constitute the largest sinusoidal vascular bed of the body. LSEC are considered the most active endocytes of mammals and maintain blood and tissue homeostasis. Genetic ablation of LSEC-characteristic scavenger receptors Stab1 and Stab2 causes severe renal glomerulosclerosis and albuminuria by altering the molecular composition of the blood plasma. Preliminary data indicate that Stabilin-dependent circulating molecules can have either protective or harmful functions in different physiologic and pathophysiologic settings. The opposite roles of Stab1- and Stab2- mediated clearance during metabolic and fibrotic diseases will be the focus of this project. Elucidation of the underlying mechanisms that provide protection and confer susceptibility to atherosclerosis, organ fibrosis and skin inflammation, respectively, will advance our understanding of systemic angiocrine effects and we envision to establish proof-of-concept for Stabilin-targeted therapies.
For the project, structured PhD training will be provided in Collaborative Research Center 1366 “Vascular Control of Organ Function”, funded by the Deutsche Forschungsgemeinschaft (DFG) and starting Jan 1, 2019 and by the Research Training Group of the DFG, RTG 2099 “Hallmarks of Skin Cancer”.
References:
• Wohlfeil SA, et al Hepatic endothelial Notch activation protects against liver metastasis by regulating endothelial-tumor cell adhesion independent of angiocrine signaling. Cancer Res, 2018.

• Leibing T, et al. Angiocrine Wnt signaling controls liver growth and metabolic maturation in mice. Hepatology 68: 707-722, 2018

• Géraud C, et al. Gata4-dependent organ-specific endothelial differentiation controls liver development and embryonic hematopopiesis. J Clin Invest 127: 1099-1114, 2017.

• Koch PS, et al. Angiocrine Bmp2 signaling in murine liver controls normal iron homeostasis. Blood 29: 415-419, 2017.

• Géraud C, et al. The metastatic cycle: metastatic niches and cancer cell dissemination. J Dtsch Dermatol Ges. 12(11):1012-9, 2014.

• Géraud C, et al. Vascular niches: endothelial cells as tissue- and site-specific multifunctional team players in health and disease. J Dtsch Dermatol Ges. 12(8):685-9, 2014.
Methods that will be used:
• In vivo: working with knockout mice, murine models of organ diseases (metabolic and inflammatory diseases such as organ fibrosis, atherosclerosis an skin inflammation), isolation of primary endothelial cells, Histology and Immunohistochemistry.

• In vitro: a broad array of methods of molecular biology, protein biochemistry and cell culture techniques.
Cooperation partners:
• Laboratories within the Collaborative Research Center / Sonderforschungsbereich 1366 “Vascular Control of Organ Function” and within GRK/RTG 2099/1 (http://www.rtg2099.de/)

• close connections to laboratories within the DKFZ Heidelberg (Prof. Dr. H. Augustin) and the Medical Faculty Mannheim (Prof. Dr. S. Goerdt, Dr. P. Koch, Prof. Dr. A. Cerwenka, Prof. Dr. J. Heinecke)
Personal qualifications:
• We are looking for highly motivated candidates with interest in organ-specific vascular biology and its impact on organ dysfunction

• we can offer you:
o a structured PhD-training within the Research Training Group (RTG) 2099; https://www.umm.uni-heidelberg.de/rtg2099/ and the CRC1366 embedded School of Angioscience.
o a broad scientific background
o close mentoring and structured support
o stimulating team-work environment
o an excellent start to your scientific career
Keywords:
Vascular biology, angiokines, vascular niche, organ fibrosis, metabolic disease, atherosclerosis, metastasis, skin inflammation, liver