Investigator, Lady Davis Institute Assistant Professor, Department of Oncology, McGill University
Dr. Josie Ursini-Siegel is an Assistant Professor at the Lady Davis Institute for Medical Research, a member of the Jewish General Hospital/Segal Cancer Center and the Department of Oncology at McGill University. Cancer cells induce the recruitment of, and are interdispersed within, a tumor stroma that includes fibroblasts, endothelial cells, immune cells and extracellular matrix components. Indeed, an activated stroma promotes breast cancer progression and facilitates metastatic spread, the most devastating aspect of this disease. Dr. Ursini-Siegel is interested in understanding the mechanism by which the ShcA adaptor protein regulates signal transduction pathways in breast cancer cells to facilitate communication with the local microenvironment and promote the establishment of a pro-tumorigenic reactive stroma. To achieve this, she utilizes a genetic approach to alter ShcA signalling or expression in well characterized transgenic breast cancer mouse models.
Major Research Activites
Dr. Ursini-Siegel’s research interests include:
- Defining the mechanism by which ShcA signaling in breast cancer cells controls both tumor neovascularization and blood vessel integrity.
- Defining the mechanism by which ShcA signaling in breast cancer cells establishes a local immunosuppressive state to favour cancer progression.
- Translate the SRIS into a clinically-relevant diagnostic tool to predict the outcome of HER2 and basal breast cancer patients. This has enormous clinical potential since there is currently no screening test to stratify these patients within these subtypes based on outcome.
- Identify the contribution of the individual ShcA isoforms during breast cancer progression.
Ursini-Siegel J, Hardy WR, Zheng Y, Ling C, Zuo D, Zhang C, Podmore L, Pawson T, Muller WJ. The ShcA SH2 domain engages a 14-3-3/PI3'K signaling complex and promotes breast cancer cell survival. Oncogene. 2012 Jan 30. doi: 10.1038/onc.2012.4.
Kristensen VN, Vaske CJ, Ursini-Siegel J, Van Loo P, Nordgard SH, Sachidanandam R, Sørlie T, Wärnberg F, Haakensen VD, Helland Å, Naume B, Perou CM, Haussler D, Troyanskaya OG, Børresen-Dale AL. Integrated molecular profiles of invasive breast tumors and ductal carcinoma in situ (DCIS) reveal differential vascular and interleukin signaling. Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):2802-7.
Ursini-Siegel J, Cory S, Zuo D, Hardy WR, Rexhepaj E, Lam S, Schade B, Jirstrom K, Bjur E, Piccirillo CA, Denardo D, Coussens LM, Brennan DJ, Gallagher WM, Park M, Pawson T, Hallett M, Muller WJ. Receptor tyrosine kinase signaling favors a protumorigenic state in breast cancer cells by inhibiting the adaptive immune response. Cancer Res. 2010 Oct 15;70(20):7776-87.
Ursini-Siegel J, Hardy WR, Zuo D, Lam SH, Sanguin-Gendreau V, Cardiff RD, Pawson T, Muller WJ. ShcA signalling is essential for tumour progression in mouse models of human breast cancer. EMBO J. 2008 Mar 19;27(6):910-20.