Hunt, Pat
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Research Interests

Research in our laboratory focuses on mammalian germ cell development with the aim of increasing our understanding of the genetic control of sex determination and of the meiotic process in mammals. Our research involves studies of both humans and mice.

We are conducting studies of human oocytes in association with the Department of Reproductive Biology at University Hospitals. The aim of this research is to elucidate the basis of the maternal age effect in the human female; that is, to determine why, as women age, they are at an increased risk of producing chromosomally abnormal children. Although we know that the maternal age effect is the result of meiotic errors in the egg and that most errors occur during the completion of the first meiotic division (around the time of ovulation), the mechanism by which age increases the frequency of errors remains unknown. Recent studies in our laboratory suggest that, with increasing age, the growth process of the human oocyte may become perturbed (Volarcik et al., 1998). Hence one goal of our research is to understand how changes in the environment in which the oocyte undergoes its final growth and maturation effect the meiotic process.

In addition, we are studying a number of different mouse mutants to understand the genetic control of the meiotic cell cycle in mammals and the factors that influence meiotic chromosome alignment and segregation. These studies make use of new techniques for the in vitro growth of murine follicles, the production of chimeric ovaries, the analysis of meiotic cell cycle progression and the analysis of meiotic chromosome behavior. Our recent studies suggest that the control of mammalian female meiosis differs in fundamental respects from both male meiosis and mitosis and that these differences may provide a key to understanding the high error rate in female meiosis (LeMaire-Adkins et al., 1997).

Publications

Hunt, P.A., Koehler, K.E., Susiarjo, M., Hodges, C.A., Ilagan, A., Voigt, R.C., Thomas, S., Thomas, B.F., Hassold, T.J., Bisphenol A causes meiotic aneuploidy in the female mouse, Current Biology, 13:546-553, 2003

Koehler, K.E., Voigt, R.C., Thomas, S., Lamb, B., Urban, C., Hassold, T., Hunt, P.A., When disaster strikes: Rethinking caging materials, Lab Animal, 32(4):24-27, 2003

Theunissen, J. F., Kaplan, M.I., Hunt, P.A., Williams, B.R., Ferguson, D.O., Alt, F.W., Petrini, J.H.J., Checkpoint failure and chromosomal instability without lymphomagenesis in Mre11ATLD1/ATLD1 mice, Molecular Cell12:1-20, 2003

Revenkova, E., Eijpe, M., Heyting, C., Hodges, C.A., Hunt, P.A., Liebe, B., Scherthan, H., Jessberger, R., Cohesin SMC1 beta is required for meiotic chromosome dynamics, sister chromatid cohesion and DNA recombination, Nature Cell Biology, 6(6):555-62, 2004

Cherry, S.M, Hunt, P.A, Hassold, T.J., Cisplatin disrupts mammalian spermatogenesis, but does not affect recombination or chromosome segregation, Mutation Research 564(2):115-128, 2004

Lynn, A., Schrump, St. Cherry, J., Hassold, T, Hunt, P.  Sex, not genotype, determines recombination levels in mice, American Journal of Human Genetics, 77:670-675, 2005.

Hodges, C.A., Revenkova, E., Jessberger, R., Hassold, T.J., Hunt, P.A., SMC1b-deficient female mice provide evidence that cohesins are a missing link in age-related nondisjunction, Nature Genetics 37(12):1351-1355, 2005

Hall, H., Hunt, P., Hassold, T., Meiosis and sex chromosome aneuploidy: how meiotic errors cause aneuploidy, how aneuploidy causes meiotic errors, Current Opinion in Genetics and Development, 16:323-329, 2006.

Koehler, K.E., Schrump, S.E., Cherry, J.P., Hassold, T.J., Hunt, P.A.,  Near-human aneuploidy levels in female mice with homeologous chromosomes. Current Biology, 16(15):R579-80, 2006
Hunt, P.A. Meiosis in mammals: recombination, non-disjunction and the environment.  Biochem Soc Trans, 34(Pt)4):574-7, 2006

Susiarjo, M., Hassold, T.J., Freeman, Hunt, P.A., Bisphenol A Exposure In Utero Disrupts Early Oogenesis in the Mouse, Plos Genetics, 3(1); 2007

Cherry, S.M., Adelman, C.A., Theunissen, J.W., Hassold, T.J., Hunt, P.A., Petrini, J. H., The Mre11 Complex Influences DNA Repair, Synapsis and Crossover Control in Murine Meiosis, Current Biology, 17(4):373-378, 2007.

Perez, G.I., Jurisicova, A., Wise, L., Lipina, T., Kanisek, M., Bechard, A., Takai, Y., Hunt, P., Roder, J., Grynpas, M., Tilly, J., Absence of the pro-apoptotic Bax protein extends fertility ad alleviates age-related health complications in female mice, PNAS, 104(12):5229-34, 2007.

Johnson, M.T., Freeman, E.A., Gardner, D.K., Hunt, P.A.,  Oxidative metabolism of pyruvate is required for meiotic maturation of murine oocytes in vivo,  Biology of Reproduction, in press.