James Gusella, PhD

James Gusella, PhD

Massachusetts General Hospital
Harvard Medical School
James Gusella, PhD

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.