1) Name – Title of the research project in CCHD
Dontscho Kerjaschki - Molecular Analysis of Lymphatic Endothelial Cells
2) Coordinates of the Faculty Member
Clinical Institute of Pathology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria; phone +43 1 40400 5176; fax +43 1 40400 5193, e-mail dontscho.kerjaschki@meduniwien.ac.at
3) Keywords
Lymphatic endothelial cells, lymph vessels, podoplanin, lymphoid neoangiogenesis, macrophages, glomerular diseases, podocytes, renal inflammation and allograft rejection, kidney transplants
4) Research interest of the Faculty Member
Dr. Kerjaschki is interested in the molecular mechanisms and functional aspects of the interaction of tumour- and inflammatory cells with lymphatic endothelial cells. Lymphatic endothelial cell biology and pathology have become “hot” areas of research in the last few years because it was possible to isolate lymphatic endothelial cells, propagate them in culture, and study in detail their gene expression. A substantial part in this work has been conducted in the laboratory of Dr. Kerjaschki. The major focus of the current interest is to identify yet unidentified lymphatic markers and molecules that are significant for lymphmicroangiopathy during type 2 diabetes. Further, we are interested in molecules involved in the formation of lymphnode metastasis of malignant tumours, and to identify the molecular mechanisms of the formation of secondary and tertiary lymphatic organs which appear to be orchestrated by lymphatic vessels.
5) Collaborations within CCHD
Collaboration was established long ago with the group of B. Binder. We aim at investigating the lymphatic phenotype in knock out mice with this group. Connections also exist with E. Jensen-Jarolim’s group, who has a high expertise with the phage display technology. The immunological consequences of the lymphatic phenotype are analyzed in collaboration with H. Stockinger. For the molecular characterization of BEC and LEC homing molecules, collaborations with G. Superti-Furga will be initiated. We aim to apply mass-spectrometry or the TAP-tagging technology to analyze intracellular signalling partners of our newly identified surface molecules.
6) Collaborating research groups where PhD Students can perform their research stay
Prof. Michael Detmar, Institute of Pharmaceutical Sciences HCI H 303, Swiss Federal Institute of Technology ETH Zurich, Wolfgang-Pauli-Str. 10, CH-8093 Zürich, Switzerland.
Prof. Kari Alitalo, Molecular Cancer Biology Program, Biomedicum Helsinki, Haartman Institute, PO Box 63 (Haartmaninkatu 8), FI-00014 University of Helsinki, Finland.
7) Know-how and infrastructure of the research group
Our group has discovered the mucoprotein podoplanin as a lymphatic endothelial specific gene that now is an established marker antigen (Breiteneder-Geleff et al, 1999). We were the first to isolate and characterize lymphatic endothelial cells (Kriehuber et al, 2001) and to unravel novel processes of lymphatic neoangiogenesis (Kerjaschki et al, 2006). Podoplanin expression distinguishes lymphatic from blood vessels, but it is also expressed by certain tumour types (Hantusch et al, 2007). Recent evidence indicates that podoplanin induces tumour cell migration and invasion, leading to a phenomenon called collective tumour cell invasion (Wicki et al, 2006). Moreover, podoplanin functions as a binder of chemokines (Kerjaschki et al, J Am Soc Nephrol).
The proposed project is an ambitious combination of cell biology, molecular biology, in vivo studies and immunohistochemical techniques. The features of endothelial cells have been studied since several years in the laboratory of Prof. Kerjaschki and we are routinely using primary cultures of lymphatic endothelial cells. We are disposing of a cell culture lab to cultivate lymphatic endothelial cells and to perform cell biological assays, plus an immunofluorescence and confocal microscopy facility for visualization experiments. Further, a fully equipped molecular biology lab, a radioactivity approved lab and a standard protein chemistry lab for performing phage display, PCR and cloning and protein characterization procedures are at hand. Furthermore, in the Institute diagnostic expertise in tumour pathology is immediately at hand when evaluation of histological morphology is needed.
