Arthur L. Horwich (born 1951) is an American

biologist A biologist is a scientist who conducts research in biology. Biologists are interested in studying life on Earth, whether it is an individual Cell (biology), cell, a multicellular organism, or a Community (ecology), community of Biological inter ...

and Sterling Professor of Genetics and Pediatrics at the

Yale School of Medicine The Yale School of Medicine is the medical school of Yale University, a private research university in New Haven, Connecticut. It was founded in 1810 as the Medical Institution of Yale College and formally opened in 1813. It is the sixth-oldest m ...

. Horwich has also been a

Howard Hughes Medical Institute The Howard Hughes Medical Institute (HHMI) is an American non-profit medical research organization headquartered in Chevy Chase, Maryland with additional facilities in Ashburn, Virginia. It was founded in 1953 by Howard Hughes, an American busin ...

investigator since 1990. His research into

protein folding Protein folding is the physical process by which a protein, after Protein biosynthesis, synthesis by a ribosome as a linear chain of Amino acid, amino acids, changes from an unstable random coil into a more ordered protein tertiary structure, t ...

uncovered the action of

chaperonin HSP60, also known as chaperonins (Cpn), is a family of heat shock proteins originally sorted by their 60kDa molecular mass. They prevent misfolding of proteins during stressful situations such as high heat, by assisting protein folding. HSP60 b ...

s, protein complexes that assist the folding of other proteins; Horwich first published this work in 1989. For his scientific work Horwich has been awarded the Gairdner International Award (2004),

Louisa Gross Horwitz Prize The Louisa Gross Horwitz Prize for Biology or Biochemistry is an annual prize awarded by Columbia University to a researcher or group of researchers who have made an outstanding contribution in basic research in the fields of biology or biochemist ...

(2008),

Lasker Award In 1945 Albert Lasker and Mary Woodard Lasker created the Lasker Awards. Every year since then the award has been given to the living person considered to have made the greatest contribution to medical science or who has demonstrated public ser ...

(2011),

Shaw Prize The Shaw Prize is a set of three annual awards presented by the Shaw Prize Foundation in the fields of astronomy, medicine and life sciences, and mathematical sciences. Established in 2002 in Hong Kong, by Hong Kong entertainment mogul and p ...

(2012),

Albany Medical Center Prize The Albany Medical Center Prize in Medicine and Biomedical Research is the United States' second highest value prize in medicine and biomedical research, awarded by the Albany Medical Center. Among prizes for medicine worldwide, the Albany Medical ...

(2016), and

Breakthrough Prize The Breakthrough Prizes are a set of international awards bestowed in three categories by the Breakthrough Prize Board in recognition of scientific advances. The awards are part of several "Breakthrough" initiatives founded and funded by Yuri M ...

(2020). He is a member of the

National Academy of Sciences The National Academy of Sciences (NAS) is a United States nonprofit, NGO, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the ...

and the

American Academy of Arts and Sciences The American Academy of Arts and Sciences (The Academy) is one of the oldest learned societies in the United States. It was founded in 1780 during the American Revolution by John Adams, John Hancock, James Bowdoin, Andrew Oliver, and other ...

Early years

Horwich was born in 1951. He grew up in Oak Park, west of Chicago. In 1969, he entered

Brown University Brown University is a Private university, private Ivy League research university in Providence, Rhode Island, United States. It is the List of colonial colleges, seventh-oldest institution of higher education in the US, founded in 1764 as the ' ...

as part of a new program that combined the undergraduate degree with medical school. During medical school, Horwich studied fat cell metabolism in the laboratory of John Fain. Horwich received his A.B. in biomedical sciences in 1972 and his

M.D. A Doctor of Medicine (abbreviated MD, from the Latin ) is a medical degree, the meaning of which varies between different jurisdictions. In the United States, and some other countries, the ''MD'' denotes a professional degree of physician. This ge ...

in 1975. He graduated as valedictorian of the first class to complete the combined program. Horwich went on to do an internship and residency in pediatrics at

Yale University Yale University is a Private university, private Ivy League research university in New Haven, Connecticut, United States. Founded in 1701, Yale is the List of Colonial Colleges, third-oldest institution of higher education in the United Stat ...

. Midway through, Horwich was not sure about an entirely clinical future. After completing his residency, he joined the

Salk Institute for Biological Studies The Salk Institute for Biological Studies is a scientific research institute in the La Jolla community of San Diego, California. The independent, non-profit institute was founded in 1960 by Jonas Salk, the developer of the polio vaccine; among th ...

La Jolla, California La Jolla ( , ) is a hilly, seaside neighborhood in San Diego, California, occupying of curving coastline along the Pacific Ocean. The population reported in the 2010 census was 46,781. The climate is mild, with an average daily temperature o ...

for a postdoctoral position in molecular biology and virology. At Salk, he worked in Walter Eckhart's laboratory alongside Tony Hunter and witnessed Hunter's discovery of tyrosine phosphorylation. He credits this time with sharpening his skills as a scientist. He said, "Tony taught me the nuts and bolts of thinking about a problem."

Research

In 1981, Horwich moved back to

New Haven, Connecticut New Haven is a city of the U.S. state of Connecticut. It is located on New Haven Harbor on the northern shore of Long Island Sound. With a population of 135,081 as determined by the 2020 United States census, 2020 U.S. census, New Haven is List ...

for a postdoctoral fellowship at

Yale University School of Medicine The Yale School of Medicine is the medical school of Yale University, a private research university in New Haven, Connecticut. It was founded in 1810 as the Medical Institution of Yale College and formally opened in 1813. It is the sixth-oldest m ...

. He worked in the laboratory of Leon Rosenberg. In 1984, he moved across the hall from Rosenberg's lab to start his own laboratory as an assistant professor in the department of genetics. He still collaborated with members of the Rosenberg laboratory, including Wayne Fenton. As an independent researcher, Horwich asked whether the pathway that imports an enzyme called

ornithine transcarbamylase Ornithine transcarbamylase (OTC) (also called ornithine carbamoyltransferase) is an enzyme () that catalyzes the reaction between carbamoyl phosphate (CP) and ornithine (Orn) to form citrulline (Cit) and phosphate (Pi). There are two classes of O ...

(OTC) into the

mitochondria A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...

of mammalian cells also could work in yeast. In 1987, during a genetic screen in yeast, Horwich and his colleagues stumbled across a protein folding function inside

. In the mutant strain, proteins entered mitochondria from the

cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...

normally but then misfolded and aggregated. They named the protein encoded by the affected gene

HSP60 HSP60, also known as chaperonins (Cpn), is a family of heat shock proteins originally sorted by their 60kDa molecular mass. They prevent misfolding of proteins during stressful situations such as high heat, by assisting protein folding. HSP60 be ...

, Heat shock protein 60, because it has a mass of 60 kDa and is produced in larger quantity in response to heat. Hsp60 is found in an 850 kDa double ring assembly, each ring containing 7 copies of Hsp60. Such assemblies, known as chaperonins, also exist in other cellular compartments and are essential components, mediating protein folding under both heat shock and normal conditions. Since 1987, Horwich and his colleagues have been studying these molecules both in ''vivo'' and ''in vitro'', with particular emphasis on the Hsp60 homologue in ''E. coli'' known as GroEL. They and others found early on that a chaperonin-mediated folding reaction can be reconstituted in a test tube, and that has enabled structural and functional studies that have begun to explain how chaperonins work.

Awards and honors

* 2001: Hans Neurath Award (Protein Society Award) * 2003: Elected to the

. * 2004:

Canada Gairdner International Award The Canada Gairdner International Award is given annually by the Gairdner Foundation at a special dinner to five individuals for outstanding discoveries or contributions to medical science. Receipt of the Gairdner is traditionally considered a ...

* 2006: Stein and Moore Award (Protein Society Award) * 2007:

Wiley Prize The Wiley Prize in Biomedical Sciences is intended to recognize breakthrough research in pure or applied life science research that is distinguished by its excellence, originality and impact on our understanding of biological systems and processes. ...

, awarded jointly with

Franz-Ulrich Hartl Franz-Ulrich Hartl (born 10 March 1957) is a German biochemist and the current Executive Director of the Max Planck Institute of Biochemistry. He is known for his pioneering work in chaperone-mediated protein folding. Early life and educati ...

* 2008:

Rosenstiel Award The Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Research is awarded by Brandeis University. It was established in 1971 "as an expression of the conviction that educational institutions have an important role to play in the en ...

, awarded jointly with Hartl * 2008:

for Biology or Biochemistry,

Columbia University Columbia University in the City of New York, commonly referred to as Columbia University, is a Private university, private Ivy League research university in New York City. Established in 1754 as King's College on the grounds of Trinity Churc ...

; awarded jointly with Hartl * 2008: Elected to the

National Academy of Medicine The National Academy of Medicine (NAM), known as the Institute of Medicine (IoM) until 2015, is an American nonprofit, non-governmental organization. The National Academy of Medicine is a part of the National Academies of Sciences, Engineerin ...

* 2011:

Massry Prize The Massry Prize was established in 1996, and is administered by the Meira and Shaul G. Massry Foundation. The Prize, of $40,000 and the Massry Lectureship, is bestowed upon scientists who have made substantial recent contributions in the biomedi ...

Keck School of Medicine The USC Keck School of Medicine is the medical school of the University of Southern California. The school teaches and trains physicians, biomedical scientists and other healthcare professionals, conducts medical research, and treats patients. F ...

University of Southern California The University of Southern California (USC, SC, or Southern Cal) is a Private university, private research university in Los Angeles, California, United States. Founded in 1880 by Robert M. Widney, it is the oldest private research university in ...

* 2011:

Albert Lasker Award for Basic Medical Research The Albert Lasker Award for Basic Medical Research is one of the Lasker Award, prizes awarded by the Lasker Foundation for a fundamental discovery that opens up a new area of biomedical science. The award frequently precedes a Nobel Prize in Phys ...

, awarded jointly with Hartl * 2012:

, awarded jointly with Hartl * 2014: Honorary Doctorate of Medical Science,

. * 2016:

* 2019:

Paul Ehrlich and Ludwig Darmstaedter Prize The Paul Ehrlich and Ludwig Darmstaedter Prize is an annual award bestowed by the since 1952 for research in medicine. It carries a monetary prize of 120,000 Euro. The prize ceremony is traditionally held on the 14th of March, the birthday of Nob ...

* 2019: Dr. Paul Janssen Award for Biomedical Research, awarded jointly with Hartl * 2020:

Breakthrough Prize in Life Sciences The Breakthrough Prize in Life Sciences is a scientific award, funded by internet entrepreneurs Mark Zuckerberg and Priscilla Chan of Facebook; Sergey Brin of Google; entrepreneur and venture capitalist Yuri Milner; and Anne Wojcicki, one of t ...

* 2021: Elected to the

* 2022: Human Frontier Science Program Nakasone Award * 2023:

BBVA Foundation Frontiers of Knowledge Award The BBVA Foundation Frontiers of Knowledge Awards () are an international award programme recognizing significant contributions in the areas of scientific research and cultural creation. The categories that make up the Frontiers of Knowledge Awards ...

BBVA Foundation Frontiers of Knowledge Award 2023
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References

External links

Art Horwich Lab at Yale

Arthur Horwich Seminars: "Chaperone-Assisted Protein Folding"
{{DEFAULTSORT:Horwich, Arthur 1951 births Members of the United States National Academy of Sciences Brown University alumni Howard Hughes Medical Investigators Yale School of Medicine faculty Yale University faculty Living people Recipients of the Albert Lasker Award for Basic Medical Research Yale Sterling Professors Massry Prize recipients Alpert Medical School alumni 21st-century American biologists Members of the National Academy of Medicine