- 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 Erwin lab elucidates mechanisms underlying the interaction between genetic variation, epigenetics and retroelements that influence human brain development. We integrate human stem cell models, genomics in post-mortem tissue and computational approaches to guide therapeutic development. We previously demonstrated that the human brain exhibits extensive genetic variability due to mobile DNA elements and discovered that L1 endonuclease activity mediates large somatic copy number variants in the brain (Erwin et al, Nature Neuroscience, 2016). We recently completed the largest transcriptome analysis of post-mortem caudate nucleus in schizophrenia which implicates decreased presynaptic autoregulation as the dopamine risk factor for schizophrenia (Benjamin et al, Nature Neuroscience, 2022). We have developed stem cell models from a subset of the postmortem cohort to better understand the molecular underpinnings of human psychiatric disorders (Sawada et al, Stem Cell Research 2020). Using cerebral and a ventral forebrain organoid model that we developed, we demonstrate that striatal neurons in the patients with SCZ carry abnormalities that originated during early brain development and the ventral forebrain striatal organoid model can recapitulate a subset of neurodevelopmental phenotypes in a dish that are present in the same patient’s postmortem tissue (Sawada et al, Stem Cell Reports 2020; and Sawada et al, biorxiv 2022). We have also used human iPS models and postmortem tissue analysis to identify the pathogenic role of a human specific retroelement (SVA) in the rare neurodegenerative disorder X-linked Dystonia Parkinsonism. In addition, we have developed iPS models of placental development and demonstrated retroelement-associated processes in human trophectoderm development (Tietze et al, 2020). By elucidating these poorly understood mechanisms, we aim to identify novel targets for psychiatric and neurodegenerative disorders.
Google scholar link: https://scholar.google.com/citations?user=r1wp8XIAAAAJ&hl=en&oi=ao
Current Team Members
Tomoyo Sawada, PhD
Arthur Feltrin, PhD
Bonna Sheehan, B.S.
Taylor Evans, B.S.; PhD Student JHMI CMM
Bailey Spiegelberg, M.P.H; PhD Student JHMI Human Genetics
Hunter Giles, B.S.; PhD Student JHMI Human Genetics
Yanhong Wang, MD, Stem Cell Core
Alejandra McCord, B.S., Stem Cell Core
Kynon Jade Benjamin, PhD
Present: K99 Fellow
Bruno Araujo Torres, PhD
Present: Associate Director GSK
Laura D’Ignazio, PhD
Present: Senior Application scientist, Maxwell Biosystems
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