Department of Biology
Massachusetts Institute of Technology
Howard Hughes Medical Institute
McGovern Institute for Brain Research


 
Research: Human Disease

In collaboration with others, primarily Bob Brown of University of Massachusetts Medical School, we showed that one gene responsible for the inherited form of amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease) encodes the enzyme Cu/Zn superoxide dismutase (SOD), which catalyzes the conversion of the free radical superoxide to hydrogen peroxide. This finding is consistent with a role for free radicals in neurodegenerative disease. We are now analyzing how mutations in SOD cause ALS and seeking other genes responsible for ALS. We are also attempting to generate C. elegans models of ALS and are analyzing C. elegans models of other human genetic neurologic and/or aging disorders, including mucolipidosis type IV and a progeroid variant of Ehlers-Danlos syndrome (see MORPHOGENESIS), and screening for C. elegans genes that might define new targets for cancer chemotherapy (see SIGNAL TRANSDUCTION, CHROMATIN REMODELING AND TRANSCRIPTIONAL REGULATION). In addition, many of the genes and gene pathways we analyze in the context of C. elegans development and behavior have counterparts involved in human biology and human disease.

cup-5 mutants, which are defective in a gene similar to the human ML-IV gene (mutated in the lysosomal storage disease mucolipidosis type IV), accumulate excess lysosomes, as seen in by comparing a wild-type and a cup-5 embryo after staining with the lysosome dye LysoTracker.

Publications: Human Disease

Abstracts: Human Disease

The Horvitz Lab