Michael Reedijk

At A Glance

• Focus on understanding the mechanisms that drive abnormal activation of developmental pathways (such as Notch) in cancer
• Studying the role of developmental pathways in regulating interactions between cancer cells and “normal cells” of the tumor microenvironment
• As a clinician, the interface between our mechanistic work and patient care is stream-lined
• Strong collaborative interactions with immunologists within the institute have allowed us to sort out cross-talk between developmental pathways and the innate and adaptive immune systems in cancer progression

Short Bio

Dr. Michael Reedijk, a graduate of the Department of Microbiology and Immunology at McGill University, completed his Doctoral studies in signal transduction in the Department of Medical Genetics at the University of Toronto in 1993. Overlapping with his Ph.D studies, he completed undergraduate training in Medicine (U of T), graduating in 1995. Dr. Reedijk began specialty training at U of T in General Surgery in 1996, and became a Fellow of the Royal College of Physicians and Surgeons of Canada in 2001. After completing combined clinical (Surgical Oncology) and post-doctoral research (Hospital for Sick Children – Division of Blood and Cancer) fellowships, he began his Surgical Oncology Staff Appointments at Mount Sinai Hospital and University Health Network in 2003. Dr. Reedijk was appointed as the Director of Research, Departments of Surgical Oncology at the University Health Network and Mount Sinai Hospital in 2006. He is currently an Associate Professor in the Departments of Surgery and Medical Biophysics at the University of Toronto. His clinical practice is devoted to the surgical treatment of melanoma and malignancies of the breast. His research lab is within The Campbell Family Institute for Cancer Research/Ontario Cancer Institute at the Princess Margaret Cancer Centre where his focus is on Notch Signaling in Breast Cancer and the tumor microenvironment.

Research Synopsis

Protein-protein interactions. Contributions to landmark papers describing the mechanisms of interaction between tyrosine-phosphorylated growth factor receptors and SH2/SH3-containing intracellular signaling molecules (Embo J, Mol Cell Biol, Proc Natl Acad Sci U S A).

Identification of JAG1 as a novel prognostic marker in breast cancer. JAG1 is a ligand that activates a signaling pathway (Notch signaling cascade) that can be directly targeted with anti-Notch compounds such as γ-secretase inhibitors (GSI). In this work we showed that JAG1 is an independent predictor of outcome, even in patients who have traditionally been identified as having “good” prognosis (i.e. axillary lymph node-negative patients). Furthermore, JAG1 expression identifies patients with breast tumors of the triple negative (TN) subtype for whom there are currently no targeted therapies available. These findings make the Notch signaling pathway an attractive therapeutic target in TN breast cancer. As such, we have been involved in clinical trials to test anti-Notch compounds in cancer (Cancer Research, Gynecol Oncol, Br J Cancer, Invest New Drugs).

High throughput kinase inhibitor screens to identify drivers of Notch activation in breast cancer. In this work we have identified the TRB3 and MAPK-ERK/TGFβ pathways as fundamental Notch regulators in breast cancer (Proc Natl Acad Sci U S A).

Recent Publications

• Izrailit J, Berman HK, Datti A, Wrana JL, Reedijk M. High throughput kinase inhibitor screens reveal TRB3 and MAPK-ERK/TGFβ pathways as fundamental Notch regulators in breast cancer. Proceedings of the national academy of sciences USA. 2013: 110: pp1714-9.
• Shimizu M, Cohen B, Goldvasser P, Berman H, Virtanen C and M Reedijk. Plasminogen activator uPA is a direct transcriptional target of the JAG1-Notch receptor signaling pathway in breast cancer. Cancer Research. 2011: 71: pp 277-86.
• Cohen, B., M. Shimizu, J. Izrailit, N.F.L. Ng, Y. Bukhman, J.G. Pan, J. Dering and M. Reedijk. Cyclin D1 is a direct target of JAG1-mediated Notch signaling in breast cancer. Breast Cancer Research and Treatment 2010: 123: pp 113-124.
• Reedijk, M., D. Pinnaduwage, B.C. Dickson, A.M. Mulligan, H. Zhang, S.B. Bull, F.P. O'Malley, S.E. Egan and I.L. Andrulis. JAG1 expression, associated with basal phenotype, predicts recurrence in lymph node-negative breast cancer. Breast Cancer Research and Treatment. 2008: 111: pp 439-448.
• Dickson B.C., Mulligan A.-M., Zhang H., Lockwood G., O'Malley F.P., Egan S.E. and M. Reedijk. High-level JAG1 mRNA and protein predict poor outcome in breast cancer. Modern Pathology. 2007: 20: pp 685-693.
• Reedijk M., Odorcic S., Chang L., McCready D.R., Lockwood G., and S.E. Egan: The Notch activation system is highly expressed in human breast cancers with poor prognosis. Cancer Research. 2005: 65: pp 8530-7.