Ruprecht-Karls-Universität Heidelberg
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Goerdt_Koch0118 - Scientist (f/m) / PhD position
Project no:
Goerdt_Koch0118

Project leader:

Project supervisor:
Goerdt, Sergij
Application deadline:
31. Dec 2018
Start of PhD project:
1. Feb 2019

Project description:

Title:
Vascular Control of Metastasis
Summary:
Despite great progress in the treatment of diverse cancers by targeted therapies and immune checkpoint inhibition, many patients nevertheless die due to cancer metastasis. Notably, metastasis of different cancers is remarkably organ-specific. It is our hypothesis that organotropic metastasis is controlled by organ-specifically differentiated vascular wall cells, especially endothelial cells. As the liver is a prime organ for cancer metastasis, we have comprehensively characterized the specialized endothelium of the liver microvasculature. We could demonstrate that transcription factor Gata4 acts as a master regulator of microvascular endothelial specification in the liver and we could identify several hepatic endothelial-derived “angiocrine” factors such as Bmp2 and Wnt2 required to maintain normal liver function.
Recent work by our group showed that liver endothelial Notch activation protects against liver metastasis in colorectal cancer as well as malignant melanoma (Wohlfeil SA et al, Cancer Research, in press). The angiocrine factors, however, that control liver metastasis are insufficiently characterized. In this project, our major aim is to study of the organ-specific vascular niches of the liver and the lymph node during metastasis in order to finally develop novel anti-metastatic treatment strategies for cancer patients.
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, in press.

• 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.
Methods that will be used:
• In vivo: working with constitutive and inducible celltype-specific knockout mice, mouse melanoma metastasis models, isolation of primary endothelial cells

• In vitro: a broad array 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, 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 structured phD-training within the Research Training Group (RTG) 2099; https://www.umm.uni-heidelberg.de/rtg2099/
o a broad scientific background
o a special and close mentoring
o stimulating team-work environment
o an excellent start to your scientific career
Keywords:
Vascular biology, angiokines, vascular niche, melanoma metastasis, lymph node, liver