Ruprecht-Karls-Universität Heidelberg
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Goerdt0118 - Scientist (f/m) / PhD position
Project no:
Goerdt0118

Project leader:

Project supervisor:
Goerdt, Sergij
Application deadline:
15. Nov 2018
Start of PhD project:
1. Dec 2018

Project description:

Title:
Sinusoidal endothelial-specific mechanisms of melanoma metastasis
Summary:
During the last years microvascular endothelial cells have been considered to actively control the tissue microenvironment by creating so-called vascular niches. Paracrine acting angiocrine factors, including extracellular matrix (ECM) molecules and cell surface proteins are now recognized to regulate cell-cell interaction in vascular niches. These angiokines control organogenesis as well as organ function during health and disease. However, superordinate mechanisms for regulation of angiocrine signalling have remained elusive. We previously found Gata4 as a master regulator of microvascular sinusoidal specification in the liver and we could identify several liver angiokines and differentiation factors (e.g. Bmp2, Wnt2) required for the homeostasis of the liver vascular niche and for the whole organism.
In this project, our major aim is to study of the organ-specific vascular niches of the liver, the bone marrow and the lymph nodes and their molecular regulators and functions in physiology and pathophysiology including tumor progression and metastasis.
References:
• Leibing T, Géraud C et al. Angiocrine Wnt signaling controls liver growth and metabolic maturation in mice. Hepatology. 2017 Oct 23. doi: 10.1002/hep.29613.

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

• Koch PS, Olsavszky V et al. Angiocrine Bmp2 signaling in murine liver controls normal iron homeostasis. Blood 29: 415-419, 2017.
Methods that will be used:
• In vivo: working with constitutive and inducible celltype-specific knockout mice, isolation of primary endothelial cells
• In vitro: a broad array of molecular biology, protein biochemistry and cell culture techniques
Cooperation partners:
• Laboratories within the GRK/RTG 2099/1 (http://www.rtg2099.de/)
• close connections to laboratories within the DKFZ Heidelberg (Prof. Dr. H. Augustin, Prof. Dr. H.-R. Rodewald) and the Medical Faculty Mannheim (Prof. Dr. C. Géraud, Prof. Dr. A. Cerwenka, Prof. Dr. J. Heinecke, Prof. Dr. T Wieland)
Personal qualifications:
• We are looking for highly motivated candidates with interest in organ-specific vascular biology and metastasis
• we can offer you:
o a broad scientific background and
o a special and close mentoring in a
o stimulating team-work environment
o to provide you an excellent start to your scientific career
Keywords:
Vascular biology, liver sinusoidal endothelial cells, angiokines, vascular niche, melanoma metastasis