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Scientist: London Regional Cancer Program, London Health Sciences Centre, London, Ontario
Assistant Professor: Department of Biochemistry, University of Western Ontario, London, Ontario
Cross Appointment: Department of Oncology
London Regional Cancer Program
Room A4-136, Cancer Research Laboratory Program
790 Commissioners Rd. E.
Canada N6A 4L6
Cell cycle regulation in development and oncogenesis
Laboratory research is focused on the fundamental mechanisms that regulate the mammalian cell cycle and how they are disrupted in cancer. This is carried out by using cell culture, in vitro biochemical, and mouse gene-targeting technologies.
Regulation of Cell Proliferation in Cancer Regulation of the mammalian cell division cycle is critical to development as cell cycle exit and differentiation are intimately linked with patterning and tissue morphogenesis. Loss of proliferative control during development is catastrophic, as it leads to apoptosis and tissue degeneration. Loss of cell cycle control is also important in disease pathology, as deregulated proliferation is a defining feature of cancer.
The G1 phase of the cell cycle is the stage at which a cell can decide to replicate its DNA and divide, or exit the cell cycle. As such, understanding the molecular mechanisms that control this decision making process is central to understanding development and cancer. The master regulator of progression through the G1 phase of the cell cycle is the Retinoblastoma protein (pRB). Its function is disabled in nearly all forms of human cancer.
Despite the central role of pRB in cell cycle control, it is unclear how it interprets regulatory signals in G1 and controls cyclin dependent kinases and transcription. This deficiency stems from the fact that pRB uses a single growth suppressive domain called the ‘pocket’ to mediate most of its regulatory functions. Dissection of function within this domain has been challenging because cancer derived mutations destroy all interactions with this domain causing a myriad of functional consequences. In sum, without a concise mechanistic understanding of the retinoblastoma protein’s function, much of the regulation of cell proliferation in development and disease will remain a mystery.