Miguel Brieño-Enríquez, MD, PhD
Assistant Professor, Department of Obstetrics, Gynecology & Reproductive Sciences, Magee-Womens Research Institute
Over half a girl’s eggs die before she is even born, and the number of healthy eggs continue to decrease throughout her life. My lab and I are researching how we can keep women’s eggs healthy throughout their lives, so they can continue having healthy babies.
Miguel Brieño-Enríquez, MD, PhD
Research in Brief
Research in the Brieño-Enríquez lab focuses in the regulation of gametogenesis in human and mouse and, more specifically, the fundamental mechanisms that are required to produce viable germ cells. Our studies include the analysis of all the different stages of germs cells including primordial germ cells (PGCs), spermatocytes, oocytes, as well as how age affects them.
Regulation of Cohesin Removal Mediated by NEK1 Kinase:
The cohesin complex is essential for maintaining sister chromatid cohesion and correcting chromosome segregation in both mitosis and meiosis. In mitosis, cohesin removal is orchestrated in two steps: 1) the prophase pathway and 2) cleavage by separase. The prophase pathway depends on the proper activity of wings apart-like (WAPL). WAPL action is dependent on its interaction with regulator of cohesion maintenance, homolog B (PDS5B) and phosphorylation of Sororin. While the regulation of the prophase pathway and mechanisms that control WAPL activity have been extensively studied in mitosis, these processes have not been characterized extensively in meiosis. The serine/threonine and tyrosine dual-specificity NIMA-like kinase-1, NEK1, is highly expressed in testis and is required for accurate cohesin removal at the first meiotic division via mechanisms that were hitherto unknown. Our studies demonstrated the regulative role of NEK1 during the meiotic prophase pathway.
Transgenerational Epigenetic Effects, PGCs and Non-coding RNAs:
In mammals, Primordial Germ Cells (PGCs) give rise to the germ cell pool during fetal development. We investigate whether prenatal exposure to environmental toxicants/drugs, such as endocrine disruptors, alter PGC differentiation, alter development of the germline, and/or induce transgenerational epigenetic disorders.
Protection of Ovarian Reserve and Reproductive Aging in Mammals:
In mammals, it is generally thought that the total number of oocytes and follicles in adult ovaries is established during pre- and perinatal life. However, the number of oocytes at birth can be modulated by any number of endogenous and exogenous factors. Because naked mole-rats (NMRs, Heterocephalus glaber) reportedly demonstrate no decline in fertility and fecundity into their third decade of life, we have recently begun to study NMR ovarian development to elucidate how they accomplish this remarkable feat.
- Miguel A. Brieño-Enríquez, Stefannie L. Moak, Anyul Abud-Flores, Paula Elaine Cohen. Characterization of Telomeric Repeat-Containing RNA (TERRA) localization and protein interactions in Primordial Germ Cells of the mouse. Biol Reprod. 2018 Nov 13. doi: 10.1093/biolre/ioy243
- Miguel A. Brieño-Enríquez, Stefannie L Moak, J Kim Holloway, Paula Elaine Cohen. (2017) NIMA-related kinase 1 (NEK1) regulates the localization and phosphorylation of α-Adducin (ADD1) and Myosin X (MYO10) during meiosis. PLoS ONE 12(10): e0185780
- Miguel A. Brieño-Enríquez, Stefannie L. Moak, Melissa Toledo, Joshua J. Filter, Stephen Gray, José L. Barbero, Paula E. Cohen and J. Kim Holloway. (2016) Cohesin removal along the chromosome arms during the first meiotic division depends on a NEK1-PP1γ-WAPL axis in the mouse. Cell Reports 17:977–986.
- Miguel A. Brieño-Enríquez, Eduardo Larriba, Jesús del Mazo. (2016) Endocrine disrupters, microRNAs, and primordial germ cells: a dangerous cocktail. Fertility and Sterility 106:871-879.
- Miguel A. Brieño-Enríquez & Paula E. Cohen. (2015) Double trouble in human aneuploidy. Nature Genetics 47:696-698.
- Miguel A. Brieño-Enríquez, Jesús García-López, David B. Cárdenas, Sylvain Guibert, Elouan Cleroux, Lukas Děd, Juan de Dios Hourcade, Jana Pěknicová, Michael Weber, Jesús del Mazo. (2015) Vinclozolin exposure during mouse development induces transgenerational alteration of the miRNA expression profiles in PGCs. PLoS One. 21;10(4):e0124296.
- Miguel A. Brieño-Enríquez, Rita Reig-Viader, Lluís Cabero, Núria Toran, Flavio Martínez F, Ignasi Roig, Montserrat Garcia-Caldés M. (2012) Gene expression is altered after BPA exposure in human fetal oocyte in vitro. Molecular Human Reproduction 18:171-183.
- Miguel A. Brieño-Enríquez, Pedro Robles, Núria Camats-Tarruella, Raquel García-Cruz R, Ignasi Roig, Lluís Cabero, Flavio Martínez, Montserrat Garcia-Caldés. (2011) Human meiotic progression and recombination are affected by Bisphenol A exposition during in vitro human oocyte development. Human Reproduction 26:2807-2818.
- Miguel A. Brieño-Enríquez, Pedro Robles, Raquel García-Cruz, Ignasi Roig, Lluís Cabero, Flavio Martínez, Montserrat Garcia-Caldés. (2010) A new culture technique that allows in vitro meiotic prophase development of fetal human oocytes. Human Reproduction 2010 25:74-84.
For additional publications, visit Pubmed.
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