The research in the Anguera laboratory focuses on maintenance of X-chromosome Inactivation in the immune system and in stem cells. They also study epigenetic mechanisms involving long noncoding RNAs during early human development and placental progenitors.
Mechanisms of X-chromosome Inactivation:
We are investigating the molecular mechanisms of X-Chromosome Inactivation, and how altered dosage of X-linked genes affects early embryonic development and contributes to sex-biased disease. We focus on the autoimmune disorder lupus, which has a strong female-bias, exhibits overexpression of X-linked immune-related genes, and involves lymphocytes. We study the epigenetic status of the inactive X in female lymphocytes from humans and mice, and have made the remarkable discovery that these cells do not maintain X-Chromosome Inactivation in the same way as other female somatic cells. We were the first to discover that the inactive X has euchromatic features in female lymphocytes, which may explain the female bias in autoimmune disorders such as lupus. We also study the dynamic mechanisms of Xist RNA localization and heterochromatin mark recruitment to the inactive X following lymphocyte activation.
Long noncoding RNAs during early human development:
We are also investigating sex-specific differences during human placental development using in vitro model systems. We discovered a novel X-linked long noncoding RNA specifically expressed in human placental progenitor cells that regulates the innate immune response.
X-chromosome Inactivation, Xist RNA, epigenetics, heterochromatin, female-biased autoimmunity, B cell development, B cell quiescence and activation, T cell quiescence and activation.
Wang Jianle, Anguera Montserrat C In Vitro Differentiation of Human Pluripotent Stem Cells into Trophoblastic Cells. Journal of visualized experiments : JoVE : , 2017.Penkala Ian, Wang Jianle, Syrett Camille M, Goetzl Laura, López Carolina B, Anguera Montserrat C lncRHOXF1, a Long Noncoding RNA from the X Chromosome That Suppresses Viral Response Genes during Development of the Early Human Placenta. Molecular and cellular biology 36: 1764-75, 2016.Wang Jianle, Syrett Camille M, Kramer Marianne C, Basu Arindam, Atchison Michael L, Anguera Montserrat C Unusual maintenance of X chromosome inactivation predisposes female lymphocytes for increased expression from the inactive X. Proceedings of the National Academy of Sciences of the United States of America 113: E2029-38, 2016.Luo Mengcheng, Zhou Jian, Leu N Adrian, Abreu Carla M, Wang Jianle, Anguera Montserrat C, de Rooij Dirk G, Jasin Maria, Wang P Jeremy Polycomb protein SCML2 associates with USP7 and counteracts histone H2A ubiquitination in the XY chromatin during male meiosis. PLoS genetics 11: e1004954, 2015.Lessing D, Anguera MC, Lee JT. X chromosome inactivation and epigenetic responses to cellular reprogramming. Annu Rev Genomics Hum Genet. 14: 85-110, 2013.Anguera Montserrat C, Sadreyev Ruslan, Zhang Zhaoqing, Szanto Attila, Payer Bernhard, Sheridan Steven D, Kwok Showming, Haggarty Stephen J, Sur Mriganka, Alvarez Jason, Gimelbrant Alexander, Mitalipova Maisam, Kirby James E, Lee Jeannie T Molecular signatures of human induced pluripotent stem cells highlight sex differences and cancer genes. Cell stem cell 11: 75-90, 2012.Anguera Montserrat C, Ma Weiyuan, Clift Danielle, Namekawa Satoshi, Kelleher Raymond J, Lee Jeannie T Tsx produces a long noncoding RNA and has general functions in the germline, stem cells, and brain. PLoS genetics 7: e1002248, 2011.Kim Daniel H, Jeon Yesu, Anguera Montserrat C, Lee Jeannie T X-chromosome epigenetic reprogramming in pluripotent stem cells via noncoding genes. Seminars in cell & developmental biology 22: 336-42, 2011.Field Martha S, Anguera Montserrat C, Page Rodney, Stover Patrick J 5,10-Methenyltetrahydrofolate synthetase activity is increased in tumors and modifies the efficacy of antipurine LY309887. Archives of biochemistry and biophysics 481: 145-50, 2009.Anguera Montserrat C, Liu Matthew, Avruch Joseph, Lee Jeannie T Characterization of two Mst1-deficient mouse models. Developmental dynamics : an official publication of the American Association of Anatomists 237: 3424-34, 2008.
Ph.D (Biochemistry, Molecular and Cellular Biology) Cornell University, 2004B.A (Environmental Chemistry) University of California, San Diego, 1998