Breast cancer is a leading cause of cancer death among women. Current therapeutic strategies are aimed at controlling late stage malignant breast cancers. Although this strategy helps patients by extending their lifespan, they hardly result in a disease-free survival. Strategies to treat or control premalignant lesions and prevent development of aggressive malignant cancers are likely to provide the best opportunity for a long-term disease-free survival.

Premalignant growths have both an aberrant increase in cell number and a loss of cell architecture. The latter is a key criterion used by pathologists to identify and define cancerous tissue. While there are many treatment strategies being used or being developed that are aimed at pathways that control cell number increase, none have been aimed at pathways that control cell architecture. This is partly due to a poor understanding of the molecular mechanisms by which cell structure is deregulated during cancer development. My laboratory's goals are to understand how cell architecture, referred to as cell polarity, is disrupted during carcinoma and to identify pathways that can be targeted for therapeutic intervention.

We use a combination of mouse models and a unique organotypic, three-dimensional, cell culture method to study how cell polarity proteins and pathways regulate normal morphogenesis and how cell polarity disruption initiates cancer. Using the 3-D culture method, we recently discovered that oncogenes such as HER2/ErbB2 interact with the polarity protein Par6 to disrupt cell polarity. Interestingly, the ErbB2-Par6 pathway was not required for ErbB2 to induce cell proliferation, suggesting that pathways controlling cell proliferation and cell polarity can be uncoupled. In addition, we have discovered that deregulation of a cell polarity protein Scribble sensitized the cells to oncogenic insult and development of tumors by disrupting cell polarity and cell death without a significant effect on cell proliferation. Together these studies have identified cell polarity pathways as novel regulators of the cancer process. We are currently pursuing ways to target these pathways.

The above findings stem from the analysis of few polarity proteins; we believe that there are hundreds of proteins that regulate various aspects of cell polarity and tissue morphogenesis. Moving forward, we are conducting a methodical analysis to identify the polarity proteins that are altered in carcinoma. We are also investigating how alterations in polarity pathways disrupt normal tissue morphogenesis, how they cooperate with oncogenic events and how they regulate tumor progression. In doing so, we hope to identify cell polarity proteins and pathways that can be exploited for diagnosis and treatment of early cancers.

Additional Appointments

• Affiliate Investigator, Campbell Family Institute for Breast Cancer Research


• Lee K. and Margaret Lau Chair in Breast Cancer Research


• Member, Terry Fox-Ontario Cancer Institute for Cancer Research Selective Therapies Program