Arthur Horwich, MD
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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, 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.
Education & Training
- Intern and ResidentYale School of Medicine (1978)
- MDBrown University (1975)
Certifications
- Board CertificationAB of Medical Genetics, Genetics (1984)
- Board CertificationAB of Pediatrics, Pediatrics (1982)
Honors & Recognition
Award | Awarding Organization | Date |
---|---|---|
American Academy of Arts and Sciences | 2021 | |
Breakthrough Prize in Life Sciences 2020 | 2019 | |
Dr. Paul Janssen Award for Biomedical Research | 2019 | |
Paul Ehrlich and Ludwig Darmstaedter Prize | 2019 | |
E.B. Wilson Medal of American Society for Cell Biology | 2017 | |
Albany Prize in Medicine and Biomedical Research | 2016 | |
Honorary Doctorate of Medical Science | Brown University | 2014 |
Herbert Tabor Research Award of the ASBMB | 2013 | |
Shaw Prize in Life Science and Medicine | 2012 | |
Massry Prize | Massry Foundation | 2011 |
Lasker Award for Basic Medical Research | Albert and Mary Lasker Foundation | 2011 |
National Lecture Biophysical Society 2011 | 2011 | |
NIH Director's Lecture | 2010 | |
Rosenstiel Award for Distinguished Work in Basic Medical Science | 2008 | |
Louisa Gross Horwitz Prize | 2008 | |
Institute of Medicine | 2008 | |
Wiley Prize in Biomedical Sciences | 2007 | |
Stein and Moore Award, Protein Society | 2006 | |
Gairdner International Award | 2004 | |
National Academy of Sciences | 2003 | |
Hans Neurath Award, Protein Society | 2001 |
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)