Dr. Park’s research interests focus on the molecular mechanisms of oncogenic activation of receptor tyrosine kinases and mechanisms for cell transformation using the Met, hepatocyte growth factor (HGF) and oncoprotein as a model. Our group and others have shown that the activity of the HGF receptor is frequently altered in human cancer and have proposed new models for its mechanism of oncogenic activation. Our current work is aimed at identifying the critical molecular signals regulated by the HGF/SF receptor and receptor tyrosine kinases, in general, that contribute to tumor progression, and are suitable targets for therapeutic intervention. We have developed epithelial as well as fibroblastic and mouse models, to study at the molecular level, signals required for epithelial morphogenesis and those signals that promote the breakdown of organized epithelial structures, anchorage independent growth, tumorigenesis and invasion.
Our characterization of the receptor for Hepatocyte Growth Factor Scatter Factor, has shown that the consequence of steady state activation of signaling pathways in transformed and tumor cells is distinct from those activated following transient stimulation of the receptor by its ligand, indicating that transformation by receptor tyrosine kinases may be qualitatively different from the signaling that occurs following transient activation of that receptor. This is a complex question that requires a full understanding of how signals are integrated in normal cells and how these signals become altered in tumor cells in the context of other genetic alterations. This is particularly important for many human tumors and in particular for breast cancer where the biological consequence of receptor signals in an altered genetic background, or the consequence of activation of several receptor tyrosine kinases in the same tumor has not been examined.
Dr. Park’s research goals have now developed into a broader interest in understanding how multiple genetic alterations and epigenetic events synergize to promote tumorigenesis and progression in human breast cancer.
This research interest will interface with a breast cancer translational research initiative formed through a collaboration with multiple basic researchers at McGill and the MUHC and with surgeons, oncologists and pathologists at the MUHC. Dr. Park and colleagues aim at forming a Montreal Breast Cancer Functional Genomics Group that will employ the recent advances in strategies of genomics and proteomics, from the McGill based and worldwide research community, to identify molecular determinants of tumor prognosis, diagnosis and response to therapies. This is a large project that aims to interface developing technologies in the long term with improved patient care.