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Friday, December 13, 2019 at 12:20pm
Professor of Genetics, Director, Center for Reproductive Genomics, Associate Vice Provost for Life Sciences
Studies in our lab are focused on the regulation of meiosis in mammals, with special emphasis on how meiotic recombination is controlled. We focus primarily on the role of various DNA repair pathways, most notably the DNA mismatch repair (MMR) family. Initially characterized by their function in repair of DNA, and their role in the etiology of human colorectal cancer, the MMR family is important for genome stability in a variety of organisms. 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, as well as other DNA repair proteins such as members of the Fanconi Anemia pathway, play an essential role in directing appropriate recombination events during meiosis. A major goal of our research is to understand how these various pathways interact.
In addition to our studies of meiotic recombination, we are also interested in the unique transcriptional silencing mechanisms that exist during prophase I of meiosis. In particular, the silencing of the sex chromosomes is a hallmark of mammalian meiosis, and yet its function and mechanism remains poorly understood. Our studies are focused on elucidating the role of non-coding RNAs in this silencing phenomenon.