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Horwitz Prize Awarded for Work on Hormones

Horwitz Prize Awarded for Work on Hormones

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Columbia University will award the 2018 Louisa Gross Horwitz Prize to three scientists:

Pierre Chambon, Institute of Advanced Study at the Strasbourg University and Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Strasbourg, France

Ronald M. Evans, Salk Institute, La Jolla, Calif., and Howard Hughes Medical Institute, Chevy Chase, Md.

Bert W. O’Malley, Baylor College of Medicine, Houston, Texas

“for their discoveries of how steroid hormones regulate the behavior of distant cells.”

From left: Pierre Chambon, Ronald M. Evans, and Bert W. O’Malley

If you open up your medicine cabinet, it’s a safe bet that you’ll find a drug that targets a nuclear hormone receptor. Columbia University awards the 2018 Louisa Gross Horwitz Prize to Pierre Chambon, Ronald M. Evans, and Bert W. O’Malley for their research—spanning over 50 years—decoding how steroid hormones and nuclear receptors regulate cell function. This work has transformed our understanding of human physiology and disease.

Steroid hormones like cortisol and estrogens were first identified in the early 1900s. Researchers observed that these chemicals could travel long distances from one organ to another and that they influenced a wide variety of biological processes, including development, reproduction, growth, metabolism, and inflammation. But just how hormones worked remained a mystery for decades.

When molecular biology techniques became available in the 1960s, scientists could finally begin to more precisely probe the mechanism by which hormones act. Using these tools, O’Malley’s laboratory demonstrated that steroid hormones modify gene expression. This was a paradigm shift because until then many researchers thought that hormones worked by directly interacting with enzymes or manipulating the cell membrane. In a series of papers published between 1967 and 1972, O’Malley’s team showed that steroid hormones enter the cell and bind to nuclear receptors, a specialized protein that enters the nucleus and modifies gene activity. This tinkering of gene expression triggers biological changes in the cell and physiological changes in the body.

In the 1980s, scientists built on this work and isolated the genes that code for steroid hormone receptors. Teams led by Chambon and Evans were the first to discover and clone the genes for estrogen and cortisol receptors, respectively. Previously, researchers had predicted that the number of nuclear receptors would be small. But one of the big surprises that came from comparing the sequences of these nuclear receptors was that there were dozens of similar genes.

The laboratories of Chambon and Evans, in conjunction with others, proceeded to identify and isolate many of these related genes, mapping out a “superfamily” of 48 human nuclear receptors that collectively regulate a wide array of biological processes. Some of the genes they discovered had no hormone associated with them, and so were named “orphan receptors.” This work opened up a new field of biology and showed that a variety of molecules—not just steroid hormones, but thyroid hormones, bile acids, fatty acids, and others—could also bind to nuclear receptors to regulate the gene expression of cells over great distances in the body.

Following these seminal discoveries, subsequent work by all three scientists has continued to add important details to the molecule-by-molecule picture of how the 10 trillion cells in our body communicate with each other and stay in functional harmony. Unraveling these mysteries has given us deeper insight into the pathways that lead to a variety of human diseases. Today, drugs targeting nuclear receptors comprise 13 percent of all U.S. FDA-approved pharmaceuticals. These drugs treat everything from the most commonplace to the most serious conditions—including over-the-counter topical cortisone for skin inflammation, prescription rosiglitazone for type 2 diabetes, and tamoxifen, the most widely used cancer drug in the world.

Our ability to treat such a diverse array of diseases began with scientists who connected the dots among hormone, receptor, and gene.

A nuclear receptor complex binding to DNA. Credit: Protein Data Bank (2NLL)

Comments from Committee Chair 

Gerard Karsenty, MD, PhD, chair of the Horwitz Prize Committee and chair of the Department of Genetics & Development at Columbia University Vagelos College of Physicians and Surgeons:

“Nuclear receptors are a Rosetta Stone for physiology; their discovery and characterization helped solved mysteries about many of our most fundamental biological processes that were first unearthed nearly a century ago. The work of these three scientists has profoundly transformed our understanding of the human body and how we treat a wide range of diseases.”

  

Awardee Biographies

Pierre Chambon, MD, is professor of molecular genetics at the Institute of Advanced Study of the University of Strasbourg and group leader at the Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Strasbourg, France, emeritus professor at the Collège de France (Paris), and emeritus professor at the Faculty of Medicine of the Strasbourg University. Dr. Chambon completed his MD at the University of Strasbourg in 1958. Dr. Chambon also won the Horwitz prize in 1999 for his work in understanding the transcription of genetic material into messenger RNA. 

Ronald M. Evans, PhD, is a Howard Hughes Medical Institute investigator and professor at the Salk Institute in La Jolla, Calif. Dr. Evans received his bachelor’s degree in 1959 and completed his PhD in microbiology in 1963, both at the University of California, Los Angeles.

Bert W. O’Malley, MD, is the T.C.Thompson Distinguished Leadership Professor of Molecular and Cellular Biology and Chancellor at Baylor College of Medicine in Houston, Texas. Dr. O’Malley received his bachelor’s and medical degrees from the University of Pittsburgh in 1959 and 1963, respectively.

 

Press Contact 

Lucky Tran, PhD, +1 212-305-3689, lucky.tran@columbia.edu

 

The Louisa Gross Horwitz Prize

The Louisa Gross Horwitz Prize was established under the will of the late S. Gross Horwitz through a bequest to Columbia University. It is named in honor of the donor’s mother, Louisa Gross Horwitz, who was the daughter of Dr. Samuel David Gross (1805–89), a prominent Philadelphia surgeon who served as president of the American Medical Association and wrote “Systems of Surgery.” Of the 95 Horwitz Prize winners to date, 43 have gone on to receive Nobel Prizes. Most recently, the 2013 Horwitz Prize winners, Edvard I. Moser, PhD, and May-Britt Moser, PhD, of the Norwegian University of Science and Technology in Norway, shared the 2014 Nobel Prize in Physiology or Medicine with John Michael O’Keefe, PhD, of University College London. For a list of previous Horwitz Prize awardees, please click here.

The 2018 Louisa Gross Horwitz Prize Lectures will be held on Monday, Oct. 29, 2018, followed by an awards ceremony.

For more information about the Louisa Gross Horwitz Prize and the lectures, please visit http://www.cumc.columbia.edu/research/horwitz-prize.

 

Columbia University Irving Medical Center

Columbia University Irving Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the Vagelos College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. The campus that Columbia University Medical Center shares with its hospital partner, NewYork-Presbyterian, is now called the Columbia University Irving Medical Center.  For more information, visit cumc.columbia.edu or columbiadoctors.org.

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