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Arthur Horwich, MD

Sterling Professor of Genetics and Professor of Pediatrics; Investigator HHMI

Appointments

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 Resident
    Yale School of Medicine (1978)
  • MD
    Brown University (1975)

Honors & Recognition

AwardAwarding OrganizationDate
American Academy of Arts and Sciences2021
Breakthrough Prize in Life Sciences 20202019
Dr. Paul Janssen Award for Biomedical Research2019
Paul Ehrlich and Ludwig Darmstaedter Prize2019
E.B. Wilson Medal of American Society for Cell Biology2017
Albany Prize in Medicine and Biomedical Research2016
Honorary Doctorate of Medical ScienceBrown University2014
Herbert Tabor Research Award of the ASBMB2013
Shaw Prize in Life Science and Medicine2012
Massry PrizeMassry Foundation2011
Lasker Award for Basic Medical ResearchAlbert and Mary Lasker Foundation2011
National Lecture Biophysical Society 20112011
NIH Director's Lecture2010
Rosenstiel Award for Distinguished Work in Basic Medical Science2008
Louisa Gross Horwitz Prize2008
Institute of Medicine2008
Wiley Prize in Biomedical Sciences2007
Stein and Moore Award, Protein Society2006
Gairdner International Award2004
National Academy of Sciences2003
Hans Neurath Award, Protein Society2001

Departments & Organizations