Honours and Awards

• CRC Chair in Molecular Oncology, McGill University

• Medical Research Council of Canada, MRC Scientist Award

• National Cancer Institute of Canada, Research Scientist Award.

• Medical Research Council of Canada Fellowship. Department of Genetics, Harvard Medical School.

• Medical Research Council of Canada Studentship. Department of Microbiology and Immunology, McGill University.

• J.W. McConnell Award. Department of Microbiology and Immunology, McGill University.

• University Scholar.

• E.D.G. Murray Prize. Department of Microbiology and Immunology, McGill University.

• J.W. McConnell Award.Department of Microbiology and Immunology, McGill University.

• N.S.E.R.C. Undergraduate Scholarship. Institute of Parasitology, McGill University.

Research interests

The transition of a primary mammary epithelial cell to acquire a malignant phenotype involves multiple genetic events including the activation of dominant activating oncogenes and the inactivation of specific tumor suppressor genes. Our laboratory is interested in studying the role of the Epidermal Growth Factor Receptor (EGFR) family in the induction and progression of breast cancer. Elevated expression of the various EGFR family of receptor tyrosine kinases have been observed in a large proportion of sporadic breast cancers and their derived cell lines. For example, amplification and overexpression of the erbB2/neu proto-oncogene is observed in 20-30% of human breast cancer and correlates inversely with survival of the patient. As a primary focus of the laboratory to determine the relative contribution of the EGFR family receptors and their downstream signaling pathways in mammary gland development and in mammary tumorigenesis, we employ transgenic and gene targeting strategies (knock-out and knock-in). For example, we have generated a number of important ErbB2-induced mammary tumor models and are currently genetically dissecting the individual signaling pathways to determine their specific role in tumorigenesis and metastases. In addition, given the fact that germline inactivation of these signaling pathways result in either embryonic or perinatal lethality, we have used the Cre/LoxP recombination system to specifically inactivate each of these signaling molecules in the mammary epithelium to examine their role in mammary gland development or its relative contribution to mammary tumorigenesis. The results of our studies using a variety of biochemical, cell biology, and genetic analyses will provide invaluable insight into the molecular basis for ErbB2-mediated cancer.

Selected publications

Kim, H., Chan R., Dankort, D.L., Zou, D, Naujokas, M., Park, M. and Muller, W.J. (2005). The c-Src tyrosine kinase associates with the catalytic domain of ErbB-2”:implications for erbB-2 mediated transformation and signalling. Oncogene 24, 7599-7607

Howe,L.R., Chang, S.H., Tolle, K.C., Dillon, R., Young, L.J., Cardiff, R.D., Newman,R.A., Yang, P., Thaller, H.T., Muller, W.J., Brown, A.M., Hla, T., subbaramaiah, K., and Dannenberg, A. (2005). HER2/neu-induced mammary tumorigenesis and angiogenesis are reduced in cyclooxygenase knockout mice. Cancer Research 65, 10113-10119

Lin EY, Jones JG, Li P, Zhu L, Whitney KD, Muller WJ, Pollard JW. "Progression to malignancy in the polyoma middle T oncoprotein mouse breast cancer model provides a reliable model for human diseases." Am J Pathol. 2003 Nov;163(5):2113-26 [in process].

de Candia P, Solit DB, Giri D, Brogi E, Siegel PM, Olshen AB, Muller WJ, Rosen N, Benezra R. "Angiogenesis impairment in Id-deficient mice cooperates with an Hsp90 inhibitor to completely suppress HER2/neu-dependent breast tumors." Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12337-42. Epub 2003 Oct 02.

Siegel PM, Shu W, Cardiff RD, Muller WJ, Massague J. "Transforming growth factor beta signaling impairs Neu-induced mammary tumorigenesis while promoting pulmonary metastasis." Proc Natl Acad Sci USA . 2003 Jul 8;100(14):8430-5. Epub 2003 Jun 13.

D'Amico M, Wu K, Di Vizio D, Reutens AT, Stahl M, Fu M, Albanese C, Russell RG, Muller WJ, White M, Negassa A, Lee HW, DePinho RA, Pestell RG. "The role of Ink4a/Arf in ErbB2 mammary gland tumorigenesis." Cancer Res. 2003 Jun 15;63(12):3395-402.

Williams TM, Cheung MW, Park DS, Razani B, Cohen AW, Muller WJ, Di Vizio D, Chopra NG, Pestell RG, Lisanti MP. "Loss of caveolin-1 gene expression accelerates the development of dysplastic mammary lesions in tumor-prone transgenic mice." Mol Biol Cell. 2003 Mar;14(3):1027-42.