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

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.

Detection by PCR of the VNTR polymorphism at D4S95.
Authors: Authors: Allitto BA, Horn GT, Altherr MR, Richards B, McClatchey AI, Wasmuth JJ, Gusella JF.
Nucleic Acids Res
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Defined physical limits of the Huntington disease gene candidate region.
Authors: Authors: Bates GP, MacDonald ME, Baxendale S, Youngman S, Lin C, Whaley WL, Wasmuth JJ, Gusella JF, Lehrach H.
Am J Hum Genet
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Huntington disease-linked locus D4S111 exposed as the alpha-L-iduronidase gene.
Authors: Authors: MacDonald ME, Scott HS, Whaley WL, Pohl T, Wasmuth JJ, Lehrach H, Morris CP, Frischauf AM, Hopwood JJ, Gusella JF.
Somat Cell Mol Genet
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Dinucleotide repeat polymorphism at the debrisoquine 4-hydroxylase (CYP2D) locus.
Authors: Authors: Trofatter JA, Gusella JF, Haines JL.
Nucleic Acids Res
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Further characterization of PstI RFLPs at the acid alpha glucosidase (GAA) locus.
Authors: Authors: Tzall S, Martiniuk F, Ozelius L, Gusella J, Hirschhorn R.
Nucleic Acids Res
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Molecular pathology of gyrate atrophy of the choroid and retina due to ornithine aminotransferase deficiency.
Authors: Authors: Ramesh V, Gusella JF, Shih VE.
Mol Biol Med
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Loss of chromosome 22 alleles in human sporadic spinal schwannomas.
Authors: Authors: Fontaine B, Hanson MP, VonSattel JP, Martuza RL, Gusella JF.
Ann Neurol
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Gene linkage in familial amyotrophic lateral sclerosis: a progress report.
Authors: Authors: Brown RH, Horvitz HR, Rouleau GA, McKenna-Yasek D, Beard C, Sapp P, Haines JL, Gusella JF, Figlewicz DA.
Adv Neurol
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Different gene loci for hyperkalemic and hypokalemic periodic paralysis.
Authors: Authors: Fontaine B, Trofatter J, Rouleau GA, Khurana TS, Haines J, Brown R, Gusella JF.
Neuromuscul Disord
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Molecular genetics of neurofibromatosis 2 and related tumors (acoustic neuroma and meningioma).
Authors: Authors: Fontaine B, Rouleau GA, Seizinger BR, Menon AG, Jewell AF, Martuza RL, Gusella JF.
Ann N Y Acad Sci
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