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.

A gene encoding a fibroblast growth factor receptor isolated from the Huntington disease gene region of human chromosome 4.
Authors: Authors: Thompson LM, Plummer S, Schalling M, Altherr MR, Gusella JF, Housman DE, Wasmuth JJ.
Genomics
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Molecular genetics of Alzheimer disease amyloid.
Authors: Authors: Tanzi RE, George-Hyslop PS, Gusella JF.
J Biol Chem
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Dinucleotide repeat polymorphism (D16S285) on human chromosome 16.
Authors: Authors: Konradi C, Ozelius L, Yan W, Gusella JF, Breakefield XO.
Nucleic Acids Res
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MboI RFLP at the D4S43 (C4H) locus.
Authors: Authors: Lazarou LP, Snell RG, MacDonald ME, Gusella JF, Wasmuth JJ, Shaw DJ.
Nucleic Acids Res
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Localization of one gene for tuberous sclerosis within 9q32-9q34, and further evidence for heterogeneity.
Authors: Authors: Haines JL, Short MP, Kwiatkowski DJ, Jewell A, Andermann E, Bejjani B, Yang CH, Gusella JF, Amos JA.
Am J Hum Genet
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Complex patterns of linkage disequilibrium in the Huntington disease region.
Authors: Authors: MacDonald ME, Lin C, Srinidhi L, Bates G, Altherr M, Whaley WL, Lehrach H, Wasmuth J, Gusella JF.
Am J Hum Genet
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Detection by PCR of a VNTR polymorphism at D4S43.
Authors: Authors: Horn GT, McClatchey AI, Richards B, MacDonald ME, Gusella JF.
Nucleic Acids Res
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New DNA markers in the Huntington's disease gene candidate region.
Authors: Authors: Lin CS, Altherr M, Bates G, Whaley WL, Read AP, Harris R, Lehrach H, Wasmuth JJ, Gusella JF, MacDonald ME.
Somat Cell Mol Genet
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Generation and characterization of irradiation hybrids of human chromosome 4.
Authors: Authors: Doucette-Stamm LA, Riba L, Handelin B, Difilippantonio M, Ward DC, Wasmuth JJ, Gusella JF, Housman DE.
Somat Cell Mol Genet
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Torsion dystonia genes in two populations confined to a small region on chromosome 9q32-34.
Authors: Authors: Kwiatkowski DJ, Ozelius L, Kramer PL, Perman S, Schuback DE, Gusella JF, Fahn S, Breakefield XO.
Am J Hum Genet
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