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.

Potential molecular consequences of transgene integration: The R6/2 mouse example.
Authors: Authors: Jacobsen JC, Erdin S, Chiang C, Hanscom C, Handley RR, Barker DD, Stortchevoi A, Blumenthal I, Reid SJ, Snell RG, MacDonald ME, Morton AJ, Ernst C, Gusella JF, Talkowski ME.
Sci Rep
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The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies.
Authors: Authors: Redin C, Brand H, Collins RL, Kammin T, Mitchell E, Hodge JC, Hanscom C, Pillalamarri V, Seabra CM, Abbott MA, Abdul-Rahman OA, Aberg E, Adley R, Alcaraz-Estrada SL, Alkuraya FS, An Y, Anderson MA, Antolik C, Anyane-Yeboa K, Atkin JF, Bartell T, Bernstein JA, Beyer E, Blumenthal I, Bongers EM, Brilstra EH, Brown CW, Brüggenwirth HT, Callewaert B, Chiang C, Corning K, Cox H, Cuppen E, Currall BB, Cushing T, David D, Deardorff MA, Dheedene A, D'Hooghe M, de Vries BB, Earl DL, Ferguson HL, Fisher H, FitzPatrick DR, Gerrol P, Giachino D, Glessner JT, Gliem T, Grady M, Graham BH, Griffis C, Gripp KW, Gropman AL, Hanson-Kahn A, Harris DJ, Hayden MA, Hill R, Hochstenbach R, Hoffman JD, Hopkin RJ, Hubshman MW, Innes AM, Irons M, Irving M, Jacobsen JC, Janssens S, Jewett T, Johnson JP, Jongmans MC, Kahler SG, Koolen DA, Korzelius J, Kroisel PM, Lacassie Y, Lawless W, Lemyre E, Leppig K, Levin AV, Li H, Li H, Liao EC, Lim C, Lose EJ, Lucente D, Macera MJ, Manavalan P, Mandrile G, Marcelis CL, Margolin L, Mason T, Masser-Frye D, McClellan MW, Mendoza CJ, Menten B, Middelkamp S, Mikami LR, Moe E, Mohammed S, Mononen T, Mortenson ME, Moya G, Nieuwint AW, Ordulu Z, Parkash S, Pauker SP, Pereira S, Perrin D, Phelan K, Aguilar RE, Poddighe PJ, Pregno G, Raskin S, Reis L, Rhead W, Rita D, Renkens I, Roelens F, Ruliera J, Rump P, Schilit SL, Shaheen R, Sparkes R, Spiegel E, Stevens B, Stone MR, Tagoe J, Thakuria JV, van Bon BW, van de Kamp J, van Der Burgt I, van Essen T, van Ravenswaaij-Arts CM, van Roosmalen MJ, Vergult S, Volker-Touw CM, Warburton DP, Waterman MJ, Wiley S, Wilson A, Yerena-de Vega MC, Zori RT, Levy B, Brunner HG, de Leeuw N, Kloosterman WP, Thorland EC, Morton CC, Gusella JF, Talkowski ME.
Nat Genet
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A novel neurodevelopmental disorder associated with compound heterozygous variants in the huntingtin gene.
Authors: Authors: Rodan LH, Cohen J, Fatemi A, Gillis T, Lucente D, Gusella J, Picker JD.
Eur J Hum Genet
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A novel neurodevelopmental disorder associated with compound heterozygous variants in the huntingtin gene.
Authors: Authors: Rodan LH, Cohen J, Fatemi A, Gillis T, Lucente D, Gusella J, Picker JD.
Eur J Hum Genet
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Structural Chromosomal Rearrangements Require Nucleotide-Level Resolution: Lessons from Next-Generation Sequencing in Prenatal Diagnosis.
Authors: Authors: Ordulu Z, Kammin T, Brand H, Pillalamarri V, Redin CE, Collins RL, Blumenthal I, Hanscom C, Pereira S, Bradley I, Crandall BF, Gerrol P, Hayden MA, Hussain N, Kanengisser-Pines B, Kantarci S, Levy B, Macera MJ, Quintero-Rivera F, Spiegel E, Stevens B, Ulm JE, Warburton D, Wilkins-Haug LE, Yachelevich N, Gusella JF, Talkowski ME, Morton CC.
Am J Hum Genet
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Estrogen-related receptor gamma implicated in a phenotype including hearing loss and mild developmental delay.
Authors: Authors: Schilit SL, Currall BB, Yao R, Hanscom C, Collins RL, Pillalamarri V, Lee DY, Kammin T, Zepeda-Mendoza CJ, Mononen T, Nolan LS, Gusella JF, Talkowski ME, Shen J, Morton CC.
Eur J Hum Genet
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Permanent inactivation of Huntington's disease mutation by personalized allele-specific CRISPR/Cas9.
Authors: Authors: Shin JW, Kim KH, Chao MJ, Atwal RS, Gillis T, MacDonald ME, Gusella JF, Lee JM.
Hum Mol Genet
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Permanent inactivation of Huntington's disease mutation by personalized allele-specific CRISPR/Cas9.
Authors: Authors: Shin JW, Kim KH, Chao MJ, Atwal RS, Gillis T, MacDonald ME, Gusella JF, Lee JM.
Hum Mol Genet
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Large-scale phenome analysis defines a behavioral signature for Huntington's disease genotype in mice.
Authors: Authors: Alexandrov V, Brunner D, Menalled LB, Kudwa A, Watson-Johnson J, Mazzella M, Russell I, Ruiz MC, Torello J, Sabath E, Sanchez A, Gomez M, Filipov I, Cox K, Kwan M, Ghavami A, Ramboz S, Lager B, Wheeler VC, Aaronson J, Rosinski J, Gusella JF, MacDonald ME, Howland D, Kwak S.
Nat Biotechnol
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CSF1R mosaicism in a family with hereditary diffuse leukoencephalopathy with spheroids.
Authors: Authors: Eichler FS, Li J, Guo Y, Caruso PA, Bjonnes AC, Pan J, Booker JK, Lane JM, Tare A, Vlasac I, Hakonarson H, Gusella JF, Zhang J, Keating BJ, Saxena R.
Brain
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