Ruth Slack, PhD rslack@uottawa.ca Tel: (613) 562-5800 extension 8458 Fax: (613) 562-403 Dr.Slack's Lab Website: http://www.med.uottawa.ca/ruthslack Roger Guindon Hall (see Contact page for maps)

Affiliate Investigator, Neuroscience, Ottawa Hospital Research Institute

Professor Slack's interests lie in tumor suppressor proteins, specifically the two proteins p53 and retinoblastoma. Results of previous studies by Professor Slack, as well as those of others, suggest that the tumor suppressor p53 may function as a molecular switch leading to neuronal cell death following ischemia. Massive neuronal cell death leads to severe disability following stroke. In the advent of gene therapy, an understanding of the molecular events leading to neuronal cell death following ischemia is essential for effective genetic intervention. Professor Slack is examining the mechanism by which p53 mediates neuronal cell death and then using adenovirus-mediated gene delivery to render neurons resistant to ischemia. These investigations will provide a first step towards gene therapy approaches for the treatment of ischemia. It is hoped that in the future, these strategies will reduce the rate of neuronal cell death, and thereby reduce the disability resulting from stroke.

The retinoblastoma tumor suppressor protein pRb has recently been implicated in neuronal development and cell death. A key developmental step during neurogenesis is the decision to undergo terminal mitosis. Evidence indicates that terminal mitosis and terminal differentiation are tightly coupled and failure to exit the cell cycle results in impaired differentiation and neuronal cell death. Professor Slack is testing the hypothesis that pRb acts as a developmental switch to cause progenitor cells to exist the cell cycle and express a neuronal phenotype. The question will be approached using both transgenic mouse models and primary cultures of cortical progenitor cells that will be genetically manipulated with viral vectors. The studies will characterise the role of Rb in neurogenesis, as well as identify regulatory targets for Rb. As widespread cell death is prominent in the nervous system of pRb deficient transgenic mice, the molecular mechanism of neuronal cell death will be defined. These studies will contribute to our knowledge of neurogenesis, neurodegeneration and gene therapy.

Professor Slack is collaborating with investigators at the Montreal Neurological Institute, as well as the Neuroscience Research Institute in Ottawa.