James Gusella headshot

James Francis Gusella, Ph.D.

Bullard Professor of Neurogenetics in the Department of Genetics, Harvard Medical School
Research Staff, Massachusetts General Hospital
617-726-5724
Researcher Information

My laboratory is focused on understanding nervous system disease using molecular genetic strategies, beginning with human patients and proceeding through in vitro and modeling studies, with the ultimate goal of improving diagnosis, management and treatment.In any given disorder, the research can usually be divided into four sequential stages:

1. Determination of the chromosomal location of a gene defect, susceptibility gene or genetic modifier, usually based on linkage or association studies with polymorphic genetic markers.
2. Identification of the gene responsible for the phenotypic effect based upon its chromosomal location using a variety of genome analysis strategies.
3. Characterization of the mechanism of action based upon analysis of the allelic versions of the culprit gene in man, and in appropriate in vitro or in vivo model systems, including cultured human cells, genetically engineered mice, and lower organisms such as Drosophila and Dictyostelium.
4. Exploration of the potential for rational therapies, including genetic therapies.

We are currently searching for susceptibility and modifier genes in autism, Parkinson's disease, and Huntington's disease. As part of the Developmental Genome Anatomy Project, we also identify genes at breakpoints of balanced translocations associated with developmental abnormality. Finally we are examining the mechanism of pathogenesis of genetic defects in autism, biotin-responsive basal ganglia disease, Huntington's disease, Parkinson's disease, and neurofibromatosis, and pursuing assays to identify genetic and chemical modifiers, with the ultimate goal of contributing to effective rational therapies.

TRACE: Open-source software for quantifying somatic variation of tandem repeats by capillary electrophoresis.
Authors: Authors: Jiang A, Correia K, Gillis T, Oliver EL, Jones BP, McAllister B, Mejia Maza A, MacDonald ME, Mouro Pinto R, Wheeler VC, Gusella JF, McLean ZL.
J Huntingtons Dis
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Huntington's disease LIG1 modifier variant increases ligase fidelity and suppresses somatic CAG repeat expansion.
Authors: Authors: Lee E, Kim W, Beier DH, Lee Y, Kovalenko M, Saif F, Oliver E, Srinageshwar B, Murtha R, Andrew MA, Jiang A, Gillis T, Demelo B, Ruliera J, Lucente D, Kwak S, Lee R, Pinto RM, MacDonald ME, Gusella JF, O'Brien PJ, Wheeler VC, Seong IS.
Proc Natl Acad Sci U S A
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Clinical, in vitro, and in vivo evidence of WAPL as a novel cohesinopathy gene and phenotypic driver of 10q22.3q23.2 genomic disorder.
Authors: Authors: Boone PM, Erdin S, Mohamed A, Haghshenas S, Faour KNW, Kao E, Fu J, Auwerx C, Harripaul R, Jana B, Springer D, Hallstrom G, de Esch CEF, Denhoff E, Holmes L, Mohajeri K, Lemanski J, Kerkhof J, McConkey H, Rzasa J, McCune MJ, Levy MA, Grafstein J, Larson M, Wright Z, Beauchamp RL, Lucente D, Jamra RA, Agrawal N, Agrawal P, Andersen EF, Argilli E, Araiza R, Ballal S, Baxter MF, Bergant G, Bertsche A, Bhavsar R, Bortola DR, Bothe V, Brasch-Andersen C, Braun D, Bruel AL, Buchanan C, Burt ND, Carvalho LML, Chiriatti L, Cogne B, Collins R, Crunk A, Currall B, Delahaye-Duriez A, Delanne J, Denommé-Pichon AS, Devriendt K, Domingo A, Duncan L, Faivre L, Famularo L, Fulton A, Genetti C, Harel T, Havlovicova M, Higgs J, Houlier M, Iascone M, Immken L, Isidor B, Kaiser FJ, Karbone K, Kenna M, Khan A, Kimmig LK, Kleefstra T, Kraus EM, Krepischi ACV, Krey I, Ladda R, Lanoue L, Le Caignec C, Lewis ZK, Lima G, Lynch SA, Macek M, Maier O, Maitz S, Male A, Malikova M, McKay V, Moldovan O, Monteil D, Oliveira MM, Munasinghe J, Nakamori S, Neuser S, Nizon M, Nuttle X, O'Keefe K, Orec L, Parenti I, Peterlin B, Pfundt R, Pouncey J, Radio FC, Robert L, Rodan L, Rosenberg-Fogler H, Rosenfeld JA, Safraou H, Salani M, Schliesske S, Seaby EG, Sell S, Eliot Shearer A, Sherr E, Shillington A, Siebold D, Sinnema M, Smith L, Stegmann APA, Stevens C, Stevens S, Surette E, Tartaglia M, Taylor JC, Thompson ML, Tørring PM, Mau Them FT, Tsoulaki O, Umair M, Vanhoutte E, Vincent M, Vitobello A, von Wintzingerode L, Watt A, Wayhelova M, Wentzensen IM, Wilson W, Wojcik MH, Yuan B, Zampino G, Srivastava S, Westphal DS, Riedhammer KM, Joyce E, Yadav R, Gusella J, Tai DJC, Sadikovic B, Pfeifer KE, Talkowski ME.
medRxiv
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TRACE: Open-Source Software for Quantifying Somatic Variation of Tandem Repeats by Capillary Electrophoresis.
Authors: Authors: Jiang A, Correia K, Gillis T, Oliver EL, Jones BP, McAllister B, Maza AM, MacDonald ME, Pinto RM, Wheeler VC, Gusella JF, McLean ZL.
bioRxiv
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Genetic dissection of Huntington's disease modification by variation at RRM2B.
Authors: Authors: Lee K, Shin B, Kim M, Lee SW, Oh YM, Kim KH, Jiang A, Ko K, Gillis T, Lucente D, Lee R, Kwak S, Lee JM, Wheeler VC, Yoo AS, Gusella JF, MacDonald ME, Seong IS.
Hum Mol Genet
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CRISPR-engineered deletion of POGZ alters transcription factor binding at promoters of genes involved in synaptic signaling.
Authors: Authors: Moyses-Oliveira M, Liu Y, Erdin S, Gao D, Bhavsar R, Mohajeri K, O'Keefe K, Boone PM, Xavier G, Liao C, Li A, Yadav R, Salani M, Lucente D, Currall B, de Esch CEF, Tai DJC, Ruderfer D, Brennand KJ, Gusella JF, Talkowski ME.
bioRxiv
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Aberrant recursive splicing in a human disease locus.
Authors: Authors: Boone PM, Harripaul R, Yadav R, Grzybowski M, Hanafy MK, Lee AC, Choi EY, Collins RL, Polesskaya O, Makhortova N, Larson MO, Kayir H, Wang Y, Avila RA, Frie JA, Eed A, Albeely AM, Venmuri S, Ayoub SM, Lemanski JM, Ben-Isvy D, Zhao X, Sanchis-Juan A, Handley M, Erdin S, de Esch C, Mohajeri K, Chen C, Tovar PG, Salani M, Oliveira MM, Tai DJC, Currall B, McGraw C, Slaughenhaupt S, Doan R, Gao D, Gusella JF, Sanchez-Roige S, Young J, Khokar J, Geurts AM, Palmer AA, Talkowski ME.
bioRxiv
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Huntington's disease LIG1 modifier variant increases ligase fidelity and suppresses somatic CAG repeat expansion.
Authors: Authors: Lee E, Kim W, Beier DH, Lee Y, Kovalenko M, Saif F, Oliver E, Murtha R, Andrew MA, Gillis T, Demelo B, Srinageshwar B, Ruliera J, Lucente D, Kwak S, Lee R, Pinto RM, MacDonald ME, Gusella JF, O'Brien PJ, Wheeler VC, Seong IS.
bioRxiv
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Presenilin 1 hemizygosity has no overt deleterious phenotypic outcomes in sheep: Potential implications for therapeutic targets in Alzheimer's disease.
Authors: Authors: Mckean NE, Liu J, Rudiger SR, Kelly JM, McLaughlan C, Verma PJ, Hardy J, Gusella JF, Zetterberg H, Reid SJ, Handley RH, Lehnert K, Sutherland GT, Heslegrave A, Veleva E, Laban R, Pearson JF, Bawden SC, Snell RG.
Neurobiol Aging
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In vivo CRISPR-Cas9 genome editing in mice identifies genetic modifiers of somatic CAG repeat instability in Huntington's disease.
Authors: Authors: Mouro Pinto R, Murtha R, Azevedo A, Douglas C, Kovalenko M, Ulloa J, Crescenti S, Burch Z, Oliver E, Kesavan M, Shibata S, Vitalo A, Mota-Silva E, Riggs MJ, Correia K, Elezi E, Demelo B, Carroll JB, Gillis T, Gusella JF, MacDonald ME, Wheeler VC.
Nat Genet
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