Cohen, Paula

Associate Professor of Genetics
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Positions

Studies in our lab are focused on the role of the DNA mismatch repair (MMR) family in mammalian meiosis and recombination. Initially characterized by their function in repair of DNA, the MMR family is important for genome stability in a variety of organisms. This is illustrated by the observation that mutations in the genes encoding some MMR family members results in predisposition to colorectal cancer in the human population. Their function in meiosis is no less important, since disruption of the MMR pathway in mice leads to meiotic arrest and infertility. Our lab has been heavily involved in the analysis of MMR mouse mutants and their subsequent meiotic phenotypes, and these studies form the cornerstone of our research.

In addition to the study of meiotic mutants, our lab is also interested in the identification of key protein-protein and protein-DNA interactions during mouse meiosis in order to understand how recombination events are regulated, monitored and resolved. Failure to control the timing and frequency of recombination events results in mis-segregation, or non-disjunction, of chromosomes that results in embryos that are either not viable (resulting in miscarriage) or in offspring with genetic disorders such as trisomy 21, or Down syndrome. We hypothesize that the MMR pathway plays an essential role in directing appropriate recombination since members of this pathway are found at recombination sites and since mutations in these genes result in premature chromosome separation.

To explore the role of the MMR pathway in human meiosis, we have recently begun to examine human female meiosis at the molecular level. These studies are aimed at elucidating recombinogenic events in human oocytes since little is known of these processes in humans and since the majority of trisomic disorders are the result of meiotic errors during female meiosis. We are particularly interested in the fate of human oocytes after meiotic recombination events have been resolved and in the genetic/environmental influences on recombination proficiency in human oocytes.