Paula Cohen, PhD
Department of Biomedical Sciences
Professor of Genetics
Director, Center for Reproductive Genomics
Associate Vice Provost for Life Sciences
Department of Biomedical Sciences
Cornell University College of Veterinary Medicine
T9 014C Veterinary Research Tower, Box 17
Ithaca, NY 14853-6401
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.
Dr. Paula Cohen obtained her PhD in reproductive physiology in 1992 at the University of London, England, where she studied the endocrine regulation of implantation.
Dr. Cohen took a Postdoctoral position at the Albert Einstein College of Medicine, New York, where she focused on regulation of gonadal function in males and females, and in maturation of the hypothalamic-pituitary-gonadal axis. During this time, she become interested in germ cell biology and genome integrity, and transitioned into this area to study the roles of DNA repair proteins in mammalian meiosis. She joined the faculty of the Department of Genetics at Albert Einstein College in 2000, and then in 2004 was recruited to Cornell University, within the Department of Biomedical Sciences. In 2007, she was promoted to the rank of Associate Professor with indefinite tenure, and then was promoted to full Professor in 2013. In 2018, she became Associate Vice Provost for Life Sciences. In her own lab, Dr. Cohen has mentored 13 graduate students, 10 Postdoctoral fellows, 1 reproductive endocrinology fellow, and numerous undergraduates.
- 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
Since starting her own lab, she has received funding from NIH, the March of Dimes, the National Down Syndrome Society, and the Hereditary Diseases Foundation. More recently, she received a prized Grand Challenge grant from the Bill and Melinda Gates Foundation to investigate a new strategy for contraceptive development in men. Medical College, as well as participants from other colleges within Cornell University. In 2014, she successfully obtained a P50 grant to fund research within the CRG as part of the NICHD “National Centers for Translational Research in Reproduction and Infertility”. While at Cornell, she has received numerous merit awards for her research contributions, the Provost’s award for Distinguished Scholarship (2009), and the SUNY Chancellor’s award for Academic Excellence (2017).
In 2006, Dr. Cohen established the Center for Reproductive Genomics (CRG), the first Cornell-wide center encompassing clinicians and scientists from the College of Veterinary Medicine and from the Weill-Cornell Medical College, as well as participants from other colleges within Cornell University. She has co-authored over 60 papers, served as a regular and ad hoc member on several different NIH Study Sections, as well as several Special Emphasis panels for NICHD and NIGMS. Dr. Cohen has reviewed grants for international panels, including serving on the advisory board for the German Government’s Research Foundation for their special priority program in “Genome Haploidization” for six years, as well as for the UK Medical Research Council, the Wellcome Foundation (UK), The Telethon Foundation (Italy), and for the European Research Council. In 2016, she was elected by her peers to become the vice-Chair for the 2018 Gordon Research Conference on Meiosis and the chair for the 2020 meeting. Dr. Cohen previously served as associate editor for the journal, Chromosoma, and currently serves in that role for PLoS Genetics, and previously served on the editorial advisory board of Chromosome Research. She has participated as a lecturer and lab leader in the Frontiers in Reproduction (FIR) course at the Marine Biology Labs at Woods Hole, MA, for the past fourteen years. In 2015, she contributed the first chapter on meiosis for the 4th Edition of Knobil and Neil’s Physiology of Reproduction (Elsevier Press). She has served as the Director of Admissions for the Graduate Field in Genetics and Development, and on the steering committee for that field as well as for the graduate field of Molecular and Integrative Physiology.