Assistant Professor, Department of Biomedical Sciences, University of Pennsylvania School of Veterinary Medicine
University of Pennsylvania
School of Veterinary Medicine
3800 Spruce St., Rm 390EB
Philadelphia, PA 19104
Office: (215) 898-0567
Fax: (215) 573-6810
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.
Contribution to Science
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.
- Jianle Wang, Camille Syrett, Marianne Kramer, Arindam Basu, Michael Atchison, and Montserrat C. Anguera. (2016). “Unusual maintenance of X-chromosome Inactivation predisposes female lymphocytes for increased expression from the inactive X”. Proc Natl Acad Sci, Mar. 21, 2016. PMCID: PMC4833277
- Anguera, Montserrat C.., Sadreyev, R., Zhang, Z., Szanto, A., Sheridan, S., Haggerty, S., Jaenisch, R., Gimbelbrandt, A., Mitalipova, M., and Lee, J.T. (2012). “Molecular signatures and epigenetic stability of human induced pluripotent stem cells.” Cell Stem Cell 11(1):75-90. PMCID: PMC3587778
- Lessing, D., Anguera, Montserrat C., and Lee, J.T. (2013). “X Chromosome Inactivation and Epigenetic Responses to Cellular Reprogramming.” Annu Rev Genomics Hum Genet. 14:85-110. PMID: 23662665.
- Anguera, Montserrat C., Sun, B.K., Xu, N., and Lee, J.T. (2006). “X-Chromosome Kiss and Tell: How the Xs Go Their Separate Ways.” Cold Spring Harb Symp Quant Biol. 71:429-37.
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.
- Ian Penkala, Camille Syrett, Jianle Wang, and Montserrat C. Anguera. (2016). “LNCRHOXF1: a long noncoding RNA from the X-chromosome that suppresses viral response genes during development of the early human placenta”. Mol Cell Biol. Apr 11, 2016, PMID: 27066803. PMCID: PMC4907097.
- Jianle Wang, Montserrat C. Anguera. “In Vitro Differentiation of Human Pluripotent Stem Cells into Trophoblastic Cells”. J Vis Exp. 2017 Mar 16;(121). doi: 10.3791/55268. PMID: 28362386