Researching meiosis, the mechanisms of DNA damage detection and repair during normal development, and implications for cancer patients during 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.
Emori C, Boucher Z, Bolcun-Filas E. CHEK2 Signaling is hte Key Regulator of Oocyte Survival after Chemotherapy [preprint]. 2021 September.
Boateng R, Boechat N, Henrich PP, Bolcun-Filas E. Whole Ovary Immunofluorescence, Clearing, and Multiphoton Microscopy for Quantitative 3D Analysis of the Developing Ovarian Reserve in Mouse. J Vis Exp. 2021 Sep 3;(175). doi: 10.3791/62972. PubMed PMID: 34542534; PubMed Central PMCID: PMC8911993.
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. doi: 10.1126/science.1247671. PubMed PMID: 24482479; PubMed Central PMCID: PMC4048839.
Woodard TL, Bolcun-Filas E. Prolonging Reproductive Life after Cancer: The Need for Fertoprotective Therapies. Trends Cancer. 2016 May;2(5):222-233. doi: 10.1016/j.trecan.2016.03.006. Epub 2016 Apr 23. Review. PubMed PMID: 28741510.
Bolcun-Filas E, Handel MA. Meiosis: the chromosomal foundation of reproduction. Biol Reprod. 2018 Jul 1;99(1):112-126. doi: 10.1093/biolre/ioy021. Review. PubMed PMID: 29385397.
Powers NR, Dumont BL, Emori C, Lawal RA, Brunton C, Paigen K, Handel MA, Bolcun-Filas E, Petkov PM, Bhattacharyya T. Sexual dimorphism in the meiotic requirement for PRDM9: A mammalian evolutionary safeguard. Sci Adv. 2020 Oct;6(43). doi: 10.1126/sciadv.abb6606. Print 2020 Oct. PubMed PMID: 33097538; PubMed Central PMCID: PMC7608834.
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I investigate how females’ genetic backgrounds influence their fertility.