Honours and Awards

• Jeanne Manery Fisher Memorial Lectureship

• Diane and Sal Guerrera Chair in Cancer Genetics

• CIHR Senior Investigator

• William Dawson Scholar

• Barbara Bourne Tiffin Cancer Research Award

• MRC Scientist

• Senior Scholar, National Cancer Institute of Canada

• Fogarty Fellowship, National Cancer Institute, USA

• MRC Studentship, Glasgow University, UK

Research interests

There is increasing evidence to support the concept that the malignant behavior of some tumors is sustained by the deregulated activation of growth factor receptors. Although much is known about the signal transduction pathways that are activated following acute stimulation of cells by growth factors, little is known about the steady state balance achieved by each signal in tumor cells following receptor deregulation, and the consequence of this for tumor formation and metastasis.

My interests have focused 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. We and others have demonstrated that the activity of the HGF receptor is frequently altered in human cancer and we have proposed new models for its mechanism of oncogenic activation. Many of our research goals for the next five years are 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. For these aims 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.

From our characterization of the receptor for Hepatocyte Growth Factor Scatter Factor, we now know significantly more about signal transduction pathways involved in transformation by this receptor oncoprotein than other receptor tyrosine kinase derived oncoproteins. These studies have revealed 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. This indicates 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.

My 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. For these studies I have integrated with a multidisciplinary group of oncologists and basic scientists who are funded by a Streams of Excellence Program from the CBCRI. These individuals, situated at multiple sites throughout Canada (Vancouver, Toronto, Hamilton, Montreal), are focused on the process of the rapid transfer of discoveries made at the research level to the bedside. In these studies I will collaborate with others to establish murine models of breast cancer that integrate the complexity of genetic alterations in human breast cancer and validate how these models reflect the human disease.

These research aims are funded for the next five years through operating grants from the CIHR, NCIC and CBCRI. In my lab within the Molecular Oncology Group, and through the Departments of Biochemistry, Experimental Medicine, Medicine and Oncology I will continue to train and teach students, postdoctoral fellows and medical students in the molecular basis of neoplasia.

Selected publications

Mood K*, Saucier C*, Ishimura A, Bong YS, Lee HS, Park M and Daar IO. Oncogenic Met Receptor Induces Cell-Cycle Progresion in Xenopus Oocytes Independent of Direct Grb2 and Shc Binding or Mos synthesis, but Requires Phosphatidylinositol 3-Kinase and Raf Signaling. J. Cell. Physiol. 207:271-285, 2006. *Co-first author

Suzuki M, Mimuro H, Suzuki T, Park M, Yamamoto T, Sasakawa C. Interaction of CagA with Crk plays an important role in Helicobacter pylori-induced loss of gastric epithelial cell adhesion. JEM The Rockefeller University Press 202 (9):1235-1247. Nov 7, 2005.

Sangwan V, Paliouras GN, Cheng A, Dubé N, Tremblay ML and Park M. (2005) Protein-tyrosine Phosphatase 1B Deficiency Protects against Fas-induced Hepatic Failure. J. Biol. Chem. 281 (1):221-228, 2006.

Abella JV, Peschard P, Naujokas MA, Lin T, Saucier C, Urbé S and Park M. Met/Hepatocyte Growth Factor Receptor Ubiquitination Suppresses Transformation and is Required for Hrs Phosphorylation. Mol. Cell. Biol. 25 (21):9632-45, 2005.

Long J, Zuo D and Park M. Pc2-mediated Sumoylation of Smad-Interacting Protein 1 Attenuates Transcriptional Repression of E-Cadherin. J. Biol. Chem. 280 (42):35477-35489, 2005.

Kim H, Chan R, Dankort DL, Zuo D, Naujokas MA, Park M and Muller WJ. (2004) The c-Src tyrosine kinase associates with the catalytic domain of ErbB-2: Implications for ErbB-2 mediated signaling and transformation. Oncogene (in press)