Paula Cohen, PhD
Department of Biomedical Sciences
Professor of Genetics
Director, Center for Reproductive Genomics
Department of Biomedical Sciences
Cornell University College of Veterinary Medicine
Veterinary Research Tower T9014C, Box 17
Ithaca, NY 14853
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.
- Hilz S., Fogarty E.A., Modzelewski A.J., Cohen P.E., and Grimson A. Transcriptome profiling of the developing male germ line identifies the miR-29 family as a global regulator during meiosis. RNA Biology (2017) PMID: 27981880
- Brieño-Enriquez M.A., Moak S., Toledo M., Filter J.J., Gray S., Barbero J.L., Cohen P.E., and Holloway J.K. Cohesin removal along the chromosome arms during the first meiotic division depends on a NEK1-PP1γ-WAPL axis. Cell Reports 17:977-986 (2016) PMID: 27760328
- Hilz S., Modzelewski A.J., Cohen P.E., and Grimson A. The roles of microRNAs and siRNAs in mammalian spermatogenesis. Development 143: 3061-3073 (2016) PMID: 27578177
- Gray S., and Cohen, P.E. Control of meiotic crossovers: from double strand break formation to designation. Annual Review of Genetics 50:175-210 (2016) PMID: 27648641
- Burkhardt S., Borsos M,. Szydlowska A., Godwin J., Williams S.A., Cohen P.E., Hirota T., Saitou M., Tachibana-Konwalski K.. Chromosome Cohesion Established by Rec8-Cohesin in Fetal Oocytes Is Maintained without Detectable Turnover in Oocytes Arrested for Months in Mice. Current Biology 26(5):678-85. (2016) PMID: 26898469
- §Sun X, §Brieno-Enriquez M.A., §Cornelius A., Modzelewski A.J. Maley T.T., Campbell-Peterson K.M., Holloway J.K., & Cohen, P.E. FancJ (Brip1) loss-of-function allele results in spermatogonial cell depletion during embryogenesis and altered processing of crossover sites during meiotic prophase I in mice. §These authors contributed equally. Chromosoma 125:237-252 (2016) PMID: 26490168
- Brieno-Enriquez M.A., & Cohen P.E. Double trouble in human aneuploidy. Nature Genetics, 47:696-698 (2015). PMID: 26111508
- §Modzelewski A.J., §Hilz A., Crate E.A., Fogerty E.A., Grenier J.K., Freire R., §Cohen P.E., and §Grimson A. Dgcr8 and Dicer are essential for X and Y chromosome integrity in male meiosis. §These authors contributed equally. Journal of Cell Science, 128: 2314-2327 (2015). PMID: 25934699
- §Holloway J.K., §Sun X., Yokoo R., Villeneuve A.M., & Cohen P.E. CNTD1 is critical for defining the final population and distribution of crossovers during mammalian meiosis. §These authors contributed equally. Journal of Cell Biology 205:633-641 (2014). PMID: 24891606 [featured in an IN FOCUS article]
- Qiao H., Prasada Rao H.B., Yang Y., Fong J.H., Cloutier J.M., Deacon D.C., Nagel K.E., Swartz R.K., Strong E., Holloway, Cohen P.E., Schimenti J.C., Ward J., & Hunter N. Antagonistic roles of ubiquitin ligase HEI10 and SUMO ligase RNF212 regulate meiotic recombination. Nature Genetics. 46(2): 194-199 (2014). PMID: 24390283
Awards and Honors