In collaboration with others, primarily Bob
Brown of the Massachusetts General Hospital, 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
