- About
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About
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.
Google scholar link: https://scholar.google.com/citations?user=r1wp8XIAAAAJ&hl=en&oi=ao
Twitter: @jerwinlab
Research
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
Twitter: @jerwinlab
Team Members
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
Alumni
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
Publications
Google scholar link: https://scholar.google.com/citations?user=r1wp8XIAAAAJ&hl=en&oi=ao
Twitter: @jerwinlab
Benjamin KJ+, Arora R, Stolz JM, D’Ignazio L, Collado-Torres L, Hyde TM, Kleinman JE, Weinberger DR, Paquola ACM+, Erwin JA+*. Transcriptional and genetic sex differences for schizophrenia across the dorsolateral prefrontal cortex, hippocampus, and caudate nucleus. medRxiv. https://doi.org/10.1101/2022.09.30.22280452.
Sawada, Tomoyo+; Barbosa, André; Araujo, Bruno; McCord, Alejandra E; D’Ignazio, Laura; Benjamin, Kynon JM; Feltrin, Arthur; Arora, Ria; Brandtjen, Anna C; Kleinman, Joel E; Hyde, Thomas M; Weinberger, Daniel; Paquola, Apua CM; Erwin, Jennifer A+*. Ventral forebrain organoids derived from individuals with schizophrenia recapitulate perturbed striatal gene expression dynamics of the donor’s brains. (2022) bioRxiv, https://doi.org/10.1101/2022.05.26.493589
D’Ignazio L, Jacomini RS, Qamar B, Benjamin KJM, Arora R, Sawada T, Evans TA, Diffenderfer KE, Pankonin AR, Hendriks WT, Hyde TM, Kleinman JE, Weinberger DR, Bragg DC, Paquola ACM, and Erwin JA+. Variation in TAF1 expression in female carrier induced pluripotent stem cells and human brain ontogeny has implications for adult neostriatum vulnerability in X-linked Dystonia Parkinsonism (2022) 21 Jul 2022, ENEURO.0129-22.2022, https://10.1523/eneuro.0129-22.2022
Erwin JA, Weinberger DR. To Model Developmental Risk in a Dish. 2022 May;179(5):319-321. https:/doi.org/10.1176/appi.ajp.20220230. PubMed PMID: 35491567. The American Journal of Psychiatry
Fukuda S, Varshney A, Fowler BJ, Wang SB, Narendran S, Ambati K, Yasuma T, Magagnoli J, Leung H, Hirahara S, Nagasaka Y, Yasuma R, Apicella I, Pereira F, Makin RD, Magner E, Liu X, Sun J, Wang M, Baker K, Marion KM, Huang X, Baghdasaryan E, Ambati M, Ambati VL, Pandey A, Pandya L, Cummings T, Banerjee D, Huang P, Yerramothu P, Tolstonog GV, Held U, Erwin JA, Paquola ACM, Herdy JR, Ogura Y, Terasaki H, Oshika T, Darwish S, Singh RK, Mozaffari S, Bhattarai D, Kim KB, Hardin JW, Bennett CL, Hinton DR, Hanson TE, Röver C, Parang K, Kerur N, Liu J, Werner BC, Sutton SS, Sadda SR, Schumann GG, Gelfand BD, Gage FH, Ambati J. Cytoplasmic synthesis of endogenous Alu complementary DNA via reverse transcription and implications in age-related macular degeneration. (2021) PNAS
Benjamin KJ, Feltrin AS, Barbosa AR, Jaffe AE, Collado-Torres L, Burke EE, Shin JH, Ulrich WS, Deep-Soboslay A, Tao R, Hyde TM, Kleinman, JE, Erwin, JA+, Weinberger, DR+, & Paquola, AC + (2020). Caudate transcriptome implicates decreased presynaptic autoregulation as the dopamine risk factor for schizophrenia. (2022), Nat Neuroscience, https://doi.org/10.1038/s41593-022-01182-7. (+Co-Corresponding author)
Tietze E, Barbosa AR, Euclydes V, Cho HJ, Lee YK, Feltrin A, van de Leemput J, Di Carlo P, Sawada T, Benjamin KJ, Brentani H, Kleinman JE, Hyde TM, Weinberger DR, Ursini G, McKay R, Paquola AC, Shin JH, Erwin JA+ (2020). Single-cell analysis of human trophoblast stem cell specification reveals activation of fetal cytotrophoblast expression programs including coronavirus associated host factors and human endogenous retroviruses. bioRxiv, https://doi.org/10.1101/2020.08.29.273425.
Sawada T, Chater TE, Sasagawa Y, Yoshimura M, Fujimori-Tonou N, Tanaka K, Benjamin KJ, Paquola ACM, Erwin JA; Goda Y, Nikaido I, Kato T. Developmental excitation-inhibition inbalance underlying psychoses revealed by single-cell analysis of discordant twins-derived cerebral organoids. (2020) Mol Psychiatry. PMID: 32764691
Sawada T, Benjamin KJM, Brandtjen AC, Tietze E, Allen SJ, Paquola ACM, Kleinman JE, Hyde TM, Erwin, JA+. Generation of four postmortem dura-derived iPS cell lines from four control individuals with genotypic and brain-region-specific transcriptomic data available through the BrainSEQ consortium. (2020) Stem Cell Research.
Van den Hurk M, Erwin JA, Yeo GW, Gage FH, Bardy C. Patch-Seq Protocol to Analyze the Electrophysiology, Morphology and Transcriptome of Whole Single Neurons Derived From Human Pluripotent Stem Cells. (2018) Front Mol Neurosci. doi: 10.3389/fnmol2018.00261
Sarkar A, Mei A, Paquola ACM, Stern S, Bardy C, Klug J, Kim S, Neshat N, Kim HJ, Ku M, Shokhirev M, Adamowicz D, Marchetto MC, Jappeli R, Erwin JA, Padmanabhan K, Shtrahman M, Jin X, Fred H. Gage; Efficient generation of human CA3 neurons and modeling hippocampal neuronal connectivity in vitro. Cell Stem Cell, doi: 10.1016/j.stem.2018.04009.
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
Paquola ACM*, Erwin JA*, Gage FH, Insights into the role of somatic mosaicism in the brain. Current Opinion in Systems Biology, 2017
Erwin JA*, Paquola ACM*, Singer T, Gallina I, Novotny M, Quayle C, Bedrosian T, Butcher CR, Herdy JR, Lasken RS, Muotri AR, Gage FH (2016) L1-Associated Genomic Regions are Deleted in Somatic Cells of the Healthy Human Brain. Nature Neuroscience. doi: 10.1038/nn.4388.
Bardy C, Hurk MVD, Kakaradov B, Erwin JA, Jaeger B, Hernandez RV, Eames T, Gorris M, Santo E, Jappeli R, Barron J, Marchand C, Bryant A, Kellogg M, Lasken R, Steinbush H, Yeo GW, Gage FH (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 ACM, Venepally P, Novotny M, O’Connor C, Fitzpatrick C, Erwin JA, Hsu J, Husband D, McConnell MJ, Lasken R, and Gage FH (2016) Nuclear RNA-seq of single neurons reveals molecular signatures of activation. Nature Communications 7:12020.
Kung JT, Kesner B, An JY, Ahn JY, Cifuentes-Rojas C, Colognori D, Jeon Y, Szanto A, Del Rosario BC, Pinter SF, Erwin JA, and Lee JT (2015). Locus-Specific Targeting to the X Chromosome Revealed by the RNA Interactome of CTCF. Molecular Cell 57, 361-375.
Erwin JA, Marchetto MC, and Gage FH (2014). Mobile DNA elements in the generation of diversity and complexity in the brain. Nature Reviews Neuroscience 15, 497-506.
Erwin JA, del Rosario B, Payer B, and Lee JT (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 CJ*, Gimelbrant AA*, Erwin JA, Cheng AW, Guenther MG, Welstead GG, Alagappan R, Frampton GM, 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 JA, and Lee JT (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 JA, Song JJ, and Lee JT (2008). Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science 322, 750-756
Erwin JA, and Lee JT (2008). New twists in X-chromosome inactivation. Current Opinion In Cell Biology 20, 349-355.
Cohen DE*, Davidow LS*, Erwin JA, Xu N, Warshawsky D, and Lee JT (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.
Contact
We look forward to hearing from you. Please feel free to get in touch and we will get back to you as soon as possible.
The Erwin Lab
The Lieber Institute for Brain Development
855 North Wolfe Street
Suite 300, 3rd Floor
Baltimore, MD 21205
email: jennifer.erwin_at_libd_dot_org