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.

Inhibition by dexamethasone of commitment to erythroid differentiation in murine erythroleukemia cells.
Authors: Authors: Tsiftsoglou AS, Gusella JF, Volloch V, Housman DE.
Cancer Res
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Commitment to erythroid differentiation by friend erythroleukemia cells: a stochastic analysis.
Authors: Authors: Gusella J, Geller R, Clarke B, Weeks V, Housman D.
Cell
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Induction of erythroid differentiation in vitro by purines and purine analogues.
Authors: Authors: Gusella JF, Housman D.
Cell
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Am J Hum Genet
Authors: Authors: Inherited HTT CAG repeat length does not have a major impact on Huntington disease duration
2022 07 07; 109(7):1338-1340.
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Nat Commun
Authors: Authors: Orgo-Seq integrates single-cell and bulk transcriptomic data to identify cell type specific-driver genes associated with autism spectrum disorder
2022 06 10; 13(1):3243.
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Am J Hum Genet
Authors: Authors: Transcriptional and functional consequences of alterations to MEF2C and its topological organization in neuronal models
2022 Nov 03; 109(11):2049-2067.
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Am J Hum Genet
Authors: Authors: Tissue- and cell-type-specific molecular and functional signatures of 16p11.2 reciprocal genomic disorder across mouse brain and human neuronal models
2022 Oct 06; 109(10):1789-1813.
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NPJ Genom Med
Authors: Authors: Huntington's disease age at motor onset is modified by the tandem hexamer repeat in TCERG1
2022 Sep 05; 7(1):53.
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Cell
Authors: Authors: A cross-disorder dosage sensitivity map of the human genome
2022 Aug 04; 185(16):3041-3055.e25.
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