Arthur L Horwich MD

Sterling Professor of Genetics and Professor of Pediatrics; and Investigator HHMI

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Departments & Organizations

Affiliated Faculty

Biological and Biomedical Sciences (BBS): Molecular Cell Biology, Genetics and Development | Biochemistry, Biophysics and Structural Biology: Protein Folding, Dynamics and Degradation

Kavli Institute for Neuroscience

Pediatrics

Genetics

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Biography

Horwich received undergraduate and M.D. degrees from Brown University, trained in Pediatrics at Yale, was then a postdoctoral fellow first at Salk Institute in the Tumor Virology Laboratory, and then in Genetics at Yale, then joined the Yale faculty. His work was initially involved with protein import into mitochondria and resulted in discovery of a "folding machine" inside mitochondria, Hsp60. He has used genetic, biochemical, and biophysical tools to study the mechanism of action of these ring shaped so-called chaperonin machines that provide essential assistance to protein folding in many cellular compartments. More recently he has focused on neurodegenerative disease as caused by protein misfolding, seeking to understand how misfolded SOD1 enzyme in the cytosol of motor neurons leads to one form of ALS. His lab is modeling mutant SOD1-linked ALS in C.elegans, which paralyze with mutant but not wild-type SOD1, and in mice made transgenic for mutant and wild-type SOD1-YFP that likewise paralyze specifically with mutant transgene. Mutant mice are being analyzed at the level of EM, laser capture of motor neurons for profiling, by ES cell production and motor neuron differentiation, and by genetic modification.