Gordon A, Yoon SJ, Bicks L, Martin J, Pintacuda G, Arteaga S, Wamsley B, Guo Q, Elahi L, Dolmetsch R, Bernstein J, O’Hara R, Hallmayer J, Lage K, Pasca S, Geschwind DH. Developmental convergence and divergence in human stem cell models of autism spectrum disorder. bioRxiv [Preprint]. 2024 Apr;587492. doi: 10.1101/2024.04.01.587492.
Pioneering research in
The Geschwind Lab integrates population genetics, functional genomics, and bioinformatics with basic and clinical neuroscience to advance our understanding of neurologic and psychiatric disease pathogenesis and to accelerate treatment development.
Gene
Discovery
We work to identify genes that increase risk for autism and neurodegenerative dementia
Functional
Genomics
We use functional genomics and systems biology methods to integrate data and understand mechanisms
Disease
Modeling
We model the effects of these genes using in vitro and in vivo systems, from human neurons to mouse models
Drug
Development
We perform studies focused on developing new drugs or therapeutic approaches
Featured Research
The Autism Genetics & Human Diversity Project is investigating genetic risk for autism spectrum disorders (ASD) as well as healthcare disparities in autism services among African American families. Learn more about the Autism Genetics & Human Diversity Project here.
SSPsyGene aims to understand the impacts of mutations for over 200 genes known to contribute to neuropsychiatric and neurodevelopmental disease risk. Through a high throughput, quantitative, and multi-scale pipeline, the program will generate cell lines with mutations for each gene of interest and characterize the effects of mutation on human cortical development using 2D and 3D platforms.
Established in 2015 by the National Institute of Mental Health (NIMH), the PsychENCODE Consortium (PEC) is a multi-site investigation of the genomic basis of neuropsychiatric diseases. The aim is to create a resource of mechanistic insights to guide future therapeutic development.
CWOW aims to use multi-omics and functional genomic CRISPR screens to understand the differences in gene expression and cellular function as a result of the MAPT H1/H2 haplotype inversion, its effects on sporadic and familial tauopathies, and identification of novel therapeutic targets for the treatment of tauopathies.
A large-scale, multi-lab package (9 publications) that explores the molecular underpinnings of neuropsychiatric disease risk in human brain tissues.
Correction of Autism Risk Gene Expression Levels using CRISPR-Activation
We are leveraging advances in gene editing technology – using CRISPR-A to target regions of DNA known as enhancers that will turn up the expression of genes that cause ASD. Using stem cell-based 3D human cultures called cortical organoids, we have demonstrated the effectiveness of this approach on CHD8 and SCN2A, two of the most well-characterized ASD risk genes. Read more here.
Recent Publications
Emani PS, Liu JJ, Clarke D, Jensen M, Warrell J, Gupta C, Meng R, Lee CY, Xu S, Dursun C, Lou S, Chen Y, Chu Z, Galeev T, Hwang A, Li Y, Ni P, Zhou X; PsychENCODE Consortium‡; Bakken TE, Bendl J, Bicks L, Chatterjee T, Cheng L, Cheng Y, Dai Y, Duan Z, Flaherty M, Fullard JF, Gancz M, Garrido-Martín D, Gaynor-Gillett S, Grundman J, Hawken N, Henry E, Hoffman GE, Huang A, Jiang Y, Jin T, Jorstad NL, Kawaguchi R, Khullar S, Liu J, Liu J, Liu S, Ma S, Margolis M, Mazariegos S, Moore J, Moran JR, Nguyen E, Phalke N, Pjanic M, Pratt H, Quintero D, Rajagopalan AS, Riesenmy TR, Shedd N, Shi M, Spector M, Terwilliger R, Travaglini KJ, Wamsley B, Wang G, Xia Y, Xiao S, Yang AC, Zheng S, Gandal MJ, Lee D, Lein ES, Roussos P, Sestan N, Weng Z, White KP, Won H, Girgenti MJ, Zhang J, Wang D, Geschwind D, Gerstein M. Single-cell genomics and regulatory networks for 388 human brains. Science. 2024 May 24;384(6698):eadi5199. doi: 10.1126/science.adi5199. Epub 2024 May 24. PMID: 38781369.
Wamsley B, Bicks L, Cheng Y, Kawaguchi R, Quintero D, Margolis M, Grundman J, Liu J, Xiao S, Hawken N, Mazariegos S, Geschwind DH. Molecular cascades and cell-type specific signatures in ASD revealed by single cell genomics. Science. 2024 May 24;384(6698):eadh2602. doi: 10.1126/science.adh2602. Epub 2024 May 24. PMID: 38781372.
Wang H, Chang TS, Dombroski BA, Cheng PL, Patil V, Valiente-Banuet L, Farrell K, Mclean C, Molina-Porcel L, Rajput A, De Deyn PP, Bastard NL, Gearing M, Kaat LD, Swieten JCV, Dopper E, Ghetti BF, Newell KL, Troakes C, de Yébenes JG, Rábano-Gutierrez A, Meller T, Oertel WH, Respondek G, Stamelou M, Arzberger T, Roeber S, Müller U, Hopfner F, Pastor P, Brice A, Durr A, Ber IL, Beach TG, Serrano GE, Hazrati LN, Litvan I, Rademakers R, Ross OA, Galasko D, Boxer AL, Miller BL, Seeley WW, Deerlin VMV, Lee EB, White CL 3rd, Morris H, de Silva R, Crary JF, Goate AM, Friedman JS, Leung YY, Coppola G, Naj AC, Wang LS; PSP genetics study group; Dickson DW, Höglinger GU, Schellenberg GD, Geschwind DH, Lee WP. Whole-Genome Sequencing Analysis Reveals New Susceptibility Loci and Structural Variants Associated with Progressive Supranuclear Palsy. medRxiv [Preprint]. 2024 Jan 30:2023.12.28.23300612. doi: 10.1101/2023.12.28.23300612. PMID: 38234807; PMCID: PMC10793533.
Cirnigliaro M, Chang TS, Arteaga SA, Pérez-Cano L, Ruzzo EK, Gordon A, Bicks LK, Jung JY, Lowe JK, Wall DP, Geschwind DH. The contributions of rare inherited and polygenic risk to ASD in multiplex families. PNAS. 2023 Aug;120(31):e2215632120. doi: 10.1073/pnas.2215632120. Epub 2023 Jul 28. PMID: 37506195; PMCID: PMC10400943.
Rexach JE, Cheng Y, Chen L, Polioudakis D, Lin LC, Mitri V, Elkins A, Yin A, Calini D, Kawaguchi R, Ou J, Huang J, Williams C, Robinson J, Gaus SE, Spina S, Lee EB, Grinberg LT, Vinters H, Trojanowski JQ, Seeley WW, Malhotra D, Geschwind DH. Disease-specific selective vulnerability and neuroimmune pathways in dementia revealed by single cell genomics. bioRxiv [Preprint]. 2023 Sep 30:2023.09.29.560245. doi: 10.1101/2023.09.29.560245. PMID: 37808727; PMCID: PMC10557766.