Bar Harbor, ME
Researching meiosis, the mechanisms of DNA damage detection and repair during normal development of gametes, and implications for fertility of cancer patients after radiation and chemotherapy.
Germ cells are the only cell type that must endure extensive DNA damage in the form of programmed meiotic double-strand breaks (DSBs) during their normal development. Paradoxically, the absence of DSBs during meiosis as well as persisting unrepaired breaks are detrimental and typically result in meiotic arrest and infertility. Our research aims to understand the molecular mechanisms controlling the development of healthy gametes and how misregulation of these mechanisms can lead to reproductive disorders. In particular, we are interested in meiotic “quality checkpoints” operating in germ cells, which ensure that the correct and intact genetic information is transmitted to the next generation. The same checkpoint that monitors DSB repair during meiosis is responsible for high sensitivity of oocytes to cancer treatment. Chemo and radiation therapies can cause oocyte death and lead to premature ovarian failure and infertility. Disabling the key checkpoint kinase CHK2 preserved fertility in mice exposed to ionizing radiation, thus opening a new avenue for oncofertility research. Our goal is to further dissect the DNA damage response pathway in oocytes, helping identify additional targets for fertility preservation therapies in cancer patients.
Department of Biomedical Sciences, Cornell University, Ithaca, NY
Adv: John Schimenti
MRC Human Genetics Unit, Edinburgh, UK
Adv: Howard Cooke
Ph.D., developmental biology
Georg-August-Universitat, Institut fur Humangenetik, Gottingen, Germany
Adv: Wolfgang Engel
Jagiellonian University, Krakow, Poland
Adv: Jozefa Styrna
The Jackson Laboratory, Bar Harbor, ME
Department of Biomedical Sciences, Cornell University,
MRC Career Development Fellowship
IAESTE student exchange program at Georg-August-Universitat, Institut fur Humangenetik, Gottingen, Germany
Terri L. Woodard, Ewelina Bolcun-Filas. Prolonging Reproductive Life after Cancer: The Need for Fertoprotective Therapies. Trends in Cancer. 2016
Bolcun-Filas E, Rinaldi VD, White ME, Schimenti JC. Reversal of female infertility by Chk2 ablation reveals the oocyte DNA damage checkpoint pathway. Science. 2014 Jan 31;343(6170):533-6.
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