Objective Cancer care will be revolutionized over the next decade by the introduction of novel therapeutics that target the underlying molecular mechanisms of the disease. With the advent of human genetics, a plethora of genes have been correlated with human diseases such as cancer the SNP maps. Since the sequences are now available, the next big challenge is to determine the function of these genes in the context of the entire organism. Genetic animal models have proven to be extremely valuable to elucidate the essential functions of genes in normal physiology and the pathogenesis of disease. Using gene-targeted mice we have previously identified RANKL as a master gene of bone loss in arthritis, osteoporosis, and cancer cell migration and metastases and genes that control heart and kidney function; wound healing; diabetes; or lung injury Our primary goal is to use functional genomics in Drosophila and mice to understand cell transformation, invasion, and cancer metastases of epithelial tumors. The following projects are proposed: 1. Role of the key osteoclast differentiation factors RANKL-RANK and its downstream signalling cascade in the development of breast and prostate cancer. 2. Requirement of osteoclasts for bone metastases and stem cell niches using a new RANKfloxed allele; function of RANKL-RANK in local tumor cell invasion. 3. Role of RANKL-RANK in the central fever response to understand potential implications of future RANKL-RANK directed therapies. 4. Integration of gene targeting in mice with state-of-the art technologies in fly genetics; use of whole genome tissue-specific in vivo RNAi Drosophila libraries to identify essential and novel pathways for cancer pathogenesis using whole genome screens. 5. Role of TSPAN6, as a candidate lung metastasis gene. Identification of new cancer disease genes will allow us to design novel strategies for cancer treatment and will have ultimately impact on the basic understanding of cancer, metastases, and human health. Fields of science medical and health sciencesclinical medicineoncologyprostate cancermedical and health sciencesclinical medicinerheumatologymedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesbasic medicinemedical geneticsnatural sciencesbiological sciencesgeneticsgenomes Keywords RANKL-RANK breast cancer fever mammary gland biology metastasis osteoclast prostate cancer signal transduction whole genome drosophila genetics Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-AG-LS4 - ERC Advanced Grant - Physiology, Pathophysiology and Endocrinology Call for proposal ERC-2008-AdG See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Host institution INSTITUT FUER MOLEKULARE BIOTECHNOLOGIE GMBH EU contribution € 2 499 465,00 Address DR BOHRGASSE 3 1030 Wien Austria See on map Region Ostösterreich Wien Wien Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Administrative Contact Tanja Winkler (Ms.) Principal investigator Josef Martin Penninger (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all INSTITUT FUER MOLEKULARE BIOTECHNOLOGIE GMBH Austria EU contribution € 2 499 465,00 Address DR BOHRGASSE 3 1030 Wien See on map Region Ostösterreich Wien Wien Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Administrative Contact Tanja Winkler (Ms.) Principal investigator Josef Martin Penninger (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
