- Team Members
Jennifer Erwin is a molecular geneticist and neuroscientist who studies how environmental and genetic variations affect the human brain in health and disease. As a principal investigator at the Lieber Institute for Brain Development, her research group uses a hybrid of human stem cell models, post-mortem tissue and computational approaches to interrogate the contribution of epigenetic and somatic mosaicism to brain diseases. During her postdoctoral research in the laboratory of Fred H Gage at the Salk Institute, she discovered that the human brain exhibits extensive genetic variability. She developed single-cell sequencing strategies to define the mutational landscape of somatic brain retrotransposition in human stem cell models, human post-mortem tissue and mouse. She obtained a BSc in Biology from the Massachusetts Institute of Technology where she trained in the laboratory of Dr. Rudolf Jaenisch and Dr. Kevin Eggan. During her PhD at Harvard University in the laboratory of Dr. Jeannie T. Lee, she elucidated mechanisms of non-coding RNA mediated epigenetic regulation in stem cells. She is the recipient of several awards and fellowships including: the Charles J Epstein Trainee Award for Excellence in Human Genetics Research Semifinalist from the American Society of Human Genetics, the Hewitt Foundation Postdoctoral Fellowship, Phi Beta Kappa at MIT, and the National Science Foundation Pre-Doctoral Fellowship.
The developing human brain during prenatal life is uniquely sensitive to experience, which confer long-lasting effects. Epidemiological and neuroimaging studies have revealed that maternal stress, prenatal infection, sex and diet during this sensitive time associates with risk for developing schizophrenia, affective disorders and autism. While clinicians have studied these gene-by-environment associations for more than a century, the key underlying mechanisms linking sex and stress-responsive signals to long-lasting changes is largely unknown. There is tremendous need for a deeper understanding of these underlying molecular mechanisms in order to develop novel therapies for brain illnesses. The Erwin lab aims to better understand the mystery of how genes and the environment interact during human brain development, how this interaction impacts individuals in adult life and how it affects brain disease.
The overarching goal of the Erwin lab is to define the molecular mechanisms and environmental context in which human genomic variation influences susceptibility to complex brain disorders. Because the developing human brain is inaccessible to study and environmental experience is heterogeneous, we have limited knowledge about the genetic loci and molecular mechanisms of gene x environment interaction related to altered neural development and liability for brain disorders. The goals of the Erwin lab are to 1) develop human stem cell models of brain development with controlled environmental and genetic variations to interrogate how human brain development responds to these variations 2) define the contribution and functional consequences of stress-responsive DNA changes in the brain and 3) interrogate if placental function in response to stress mediates schizophrenia genomic risk. This work will provide insight into the origin of brain disorders, identify preventative measures and define molecular targets which could be malleable to treatment.
Ethan Tietze, MS
McConnell MJ, Moran JV, Abyzov A, Akbarian S, Bae T, Cortes-Ciriano I, Erwin JA, Fasching L, Flasch DA, Freed D, Ganz J, Jaffe AE, Kwan KY, Kwon M, Lodato MA, Mills RE, Paquola ACM, Rodin RE, Rosenbluh C, Sestan N, Sherman MA, Shin JH, Song S, Straub RE, Thorpe J, Weinberger DR, Urban AE, Zhou B, Gage FH, Lehner T, Senthil G, Walsh CA, Chess A, Courchesne E, Gleeson JG, Kidd JM, Park PJ, Pevsner J, Vaccarino FM; Brain Somatic Mosaicism Network. (2017) Intersection of diverse neuronal genomes and neuropsychiatric disease: The Brain Somatic Mosaicism Network. Science. doi: 10.1126/science.aal1641
Erwin, J.A.*, Paquola, A.C.M.*, Singer, T., Gallina, I., Novotny, M., Quayle, C., Bedrosian, T., Butcher, C.R., Herdy, J.R., Lasken, R.S., Muotri, A.R., Gage, F.H. (2016) L1-Associated Genomic Regions are Deleted in Somatic Cells of the Healthy Human Brain. Nature Neuroscience. doi: 10.1038/nn.4388. (* equal contribution)
Bardy, C., Hurk, M.V.D., Kakaradov, B., Erwin, J.A., Jaeger, B., Hernandez, R.V., Eames, T., Gorris, M., Santo, E., Jappeli, R., Barron, J., Marchand, C., Bryant, A., Kellogg, M., Lasken, R., Steinbush, H., Yeo, G.W., Gage, F.H. (2016) Single-cell transcriptome predicts the electrophysiology of mature human neurons. Molecular Psychiatry. 21(11):1573-1588
Krishnaswami SR, Grindberg RV, Novotny M, Venepally P, Lacar B, Bhutani K, Linker SB, Pham S, Erwin JA, Miller JA, Hodge R, McCarthy JK, Kelder M, McCorrison J, Aevermann BD, Fuertes FD, Scheuermann RH, Lee J, Lein ES, Schork N, McConnell MJ, Gage FH, Lasken RS. (2016) RNA-Seq from single nuclei: capturing the transcriptome of human postmortem neurons. Nature Protocols 3:499-524
Lacar, B., Linker, S., Jaeger, B., Krishnaswami, S., Barron, J., Kelder, M., Parylak, S., Paquola, A.C.M., Venepally, P., Novotny, M., O’Connor, C., Fitzpatrick, C., Erwin, J.A., Hsu, J., Husband, J., McConnell, M.J., Lasken, R., and Gage, F.H. (2016) Nuclear RNA-seq of single neurons reveals molecular signatures of activation. Nature Communications 7:12020
Kung, J.T., Kesner, B., An, J.Y., Ahn, J.Y., Cifuentes-Rojas, C., Colognori, D., Jeon, Y., Szanto, A., Del Rosario, B.C., Pinter, S.F., Erwin, J.A., and Lee, J.T. (2015). Locus-Specific Targeting to the X Chromosome Revealed by the RNA Interactome of CTCF. Molecular Cell 57, 361-375.
Erwin, J.A., Marchetto, M.C., and Gage, F.H. (2014). Mobile DNA elements in the generation of diversity and complexity in the brain. Nature Reviews Neuroscience 15, 497-506.
Erwin, J.A., del Rosario, B., Payer, B., and Lee, J.T. (2012). An ex vivo model for imprinting: mutually exclusive binding of Cdx2 and Oct4 as a switch for imprinted and random X-inactivation. Genetics 192, 857-868.
Lengner, C.J.*, Gimelbrant, A.A.*, Erwin, J.A., Cheng, A.W., Guenther, M.G., Welstead, G.G., Alagappan, R., Frampton, G.M., Xu, P., Muffat, J., Santagata S, Powers D, Barrett CB, Young RA, Lee JT, Jaenisch R, Mitalipova M (2010). Derivation of pre-X inactivation human embryonic stem cells under physiological oxygen concentrations. Cell 141, 872-883.
Erwin, J.A., and Lee, J.T. (2010). Characterization of X-chromosome inactivation status in human pluripotent stem cells. Current Protocols In Stem Cell Biology Chapter 1, Unit 1B 6.
Zhao, J., Sun, B.K., Erwin, J.A., Song, J.J., and Lee, J.T. (2008). Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science 322, 750-756
Erwin, J.A., and Lee, J.T. (2008). New twists in X-chromosome inactivation. Current Opinion In Cell Biology 20, 349-355.
Cohen, D.E.*, Davidow, L.S.*, Erwin, J.A., Xu, N., Warshawsky, D., and Lee, J.T. (2007). The DXPas34 repeat regulates random and imprinted X inactivation. Developmental Cell 12, 57-71.
Eggan, K., Rode, A., Jentsch, I., Samuel, C., Hennek, T., Tintrup, H., Zevnik, B., Erwin, J., Loring, J., Jackson-Grusby, L., Speicher MR, Kuehn R, Jaenisch R (2002). Male and female mice derived from the same embryonic stem cell clone by tetraploid embryo complementation. Nature Biotechnology 20, 455-459.
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The Erwin Lab
The Lieber Institute for Brain Development
855 North Wolfe Street
Suite 300, 3rd Floor
Baltimore, MD 21205
LIBD Speaker Series: Bryan W. Luikart, Ph.D.
Understanding the Neurobiological Basis of Autism Using PTEN as a Genetic Model Bryan W. Luikart, Ph.D. Assistant Professor Department of Molecular and Systems Biology Geisel School of Medicine at Dartmouth When: September 26 2:00pm-3:00pm Where: The Lieber Institute for Brain […]