Arthur Horwich, MD
Professor Emeritus of GeneticsCards
About
Titles
Professor Emeritus of Genetics
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, modeling mutant SOD1-linked ALS in mice transgenic for a mutant SOD1 fused with a YFP reporter. In the transgenic mutant strain, the mutant SOD1 misfolds and lodges the fusion protein in YFP fluorescent aggregates, visible in motor neurons by 2-3 months of age. These neurons are removed by microglial cells, associated with loss of ~50% of motor neurons. By 6-7 months of age the mice exhibit lower extremity paralysis, associated with loss of ~50% of the remaining motor neurons. By contrast, a wtSOD1-YFP transgenic strain with the same amount of total SOD1-YFP protein in spinal cord remains asymptomatic even after two years, and the spinal cord remains free of aggregates. An early study showed that overexpression of the molecular chaperone Hsp110, known to be part of a chaperone disaggregase, improved survival of the SOD1-YFP mice. Additional genetic modifiers are being tested.
Appointments
Other Departments & Organizations
- Biochemistry, Quantitative Biology, Biophysics and Structural Biology (BQBS)
- Genetics
- Horwich Lab
- Interdepartmental Neuroscience Program
- Kavli Institute for Neuroscience
- Molecular Cell Biology, Genetics and Development
- Neural Disorders
- Neuroscience Track
- Yale Combined Program in the Biological and Biomedical Sciences (BBS)
Education & Training
- Intern and Resident
- Yale School of Medicine (1978)
- MD
- Brown University (1975)
Board Certifications
Genetics
- Certification Organization
- AB of Medical Genetics
- Original Certification Date
- 1984
Pediatrics
- Certification Organization
- AB of Pediatrics
- Original Certification Date
- 1982
Research
Academic Achievements & Community Involvement
News
News
- December 09, 2021
Nakasone Prize Won By Arthur Horwich, MD
- April 23, 2021
American Academy of Arts & Sciences Elects Five from School of Medicine
- January 20, 2020
Horwich is 2020 Co-recipient of Breakthrough Prize
- November 05, 2019
Yale’s Horwich among researchers honored at ‘Oscars of Science’