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2020 Harrington Prize Awarded to Dr. Stuart H. Orkin, Boston Children's Hospital

Harrington Discovery Institute and The American Society for Clinical Investigation honor Dr. Orkin for his contributions to red blood cell biology


News provided by

Harrington Discovery Institute

Apr 16, 2020, 15:20 ET

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CLEVELAND, April 16, 2020 /PRNewswire/ -- The seventh annual Harrington Prize for Innovation in Medicine has been awarded to Stuart H. Orkin, MD, the David G. Nathan Distinguished Professor of Pediatrics at Harvard Medical School.

The Harrington Prize for Innovation in Medicine, established in 2014 by the Harrington Discovery Institute at University Hospitals in Cleveland, Ohio, and The American Society for Clinical Investigation (ASCI), honors physician-scientists who have moved science forward with achievements notable for innovation, creativity and potential for clinical application.

Dr. Orkin is being recognized for breakthrough discoveries on red blood cells that offer new treatments for patients with sickle cell disease and beta-thalassemia, which are among the most common genetic disorders.

Sickle cell disease (SCD), which was called the first molecular disease by Linus Pauling in 1949, is due to a mutation in the DNA encoding the beta-globin chain of hemoglobin, the molecule in red blood cells that carries oxygen and delivers it to tissues. In SCD, normal disc-like red blood cells become rigid and sickle shaped due to abnormal polymerization of sickle hemoglobin. Red cells get stuck in small blood vessels, thereby cutting off blood flow and leading to tissue damage and intense pain (a "sickle crisis"). SCD affects about 75,000 in the U.S. and millions of people throughout the world.

In SCD the adult form of hemoglobin is affected. A fetal form of hemoglobin, which is shut-off shortly after birth, is normal. Dr. Orkin discovered how the switch between fetal and adult hemoglobin is controlled, solving a longstanding mystery and suggesting new ways to reactivate normal fetal hemoglobin. Specifically, the Orkin laboratory showed that the gene BCL11A turns off fetal hemoglobin. By blocking BCL11A, fetal hemoglobin expression can be restored in the adult, offering a potential cure. In genetically engineered SCD mice, removal of BCL11A corrected red blood cell production. At Boston Children's Hospital, Dr. Orkin's colleague David A. Williams, MD, has translated these findings to patients in a gene therapy trial in which BCL11A expression is blocked. Dramatic clinical results in the first patients have validated BCL11A as a target for therapy. Promising preliminary findings of company-sponsored gene editing trials with BCL11A as a target have also been reported.

"The sickle cell community has been energized by this discovery, which is a complete game-changer for a large group of people living with SCD. Dr. Orkin's work has paved the way for testing a gene therapy approach, and potentially other approaches, to treat this debilitating disease," said W. Kimryn Rathmell, MD, PhD, Interim Chair, Department of Medicine at Vanderbilt University School of Medicine, Cornelius Abernathy Craig Professor of Medicine, and 2019-2020 President of the ASCI.

"Dr. Orkin is an extraordinary investigator and a dominant force in the fields of hematology and genetic disease. His discovery of BCL11A as a master regulator of hemoglobin gene switching, and his pursuit of application in sickle cell disease, is a prime example of how fundamental discovery can be leveraged for clinical impact," said Jonathan S. Stamler, MD, President, Harrington Discovery Institute and Robert S. and Sylvia K. Reitman Family Foundation Distinguished Chair of Cardiovascular Innovation at University Hospitals and Case Western Reserve University School of Medicine. 

A committee composed of members of the ASCI Council and the Harrington Discovery Institute Scientific Advisory Board reviewed nominations from leading academic medical centers from four countries before selecting the 2020 recipient.

In addition to receiving a $20,000 honorarium, the Harrington Prize recipient delivers The Harrington Prize Lecture at the AAP/ASCI/APSA Joint Meeting, publishes an essay in the Journal of Clinical Investigation, and speaks at the Harrington Scientific Symposium in Cleveland.

Dr. Orkin is the David G. Nathan Distinguished Professor of Pediatrics at Harvard Medical School, and an Investigator of the Howard Hughes Medical Institute. He is a principal faculty member of the Harvard Stem Cell Institute and an associate of the Broad Institute of MIT/Harvard. He received his BS from MIT and MD from Harvard Medical School. He completed pediatric hematology/oncology training at Boston Children's Hospital and the Dana-Farber Cancer Institute, and trained in the laboratory of the late Philip Leder at the National Institutes of Health.

The first recipient of The Harrington Prize for Innovation in Medicine, in 2014, was Dr. Harry Dietz (Johns Hopkins University School of Medicine, USA), for his contributions to the understanding of the biology and treatment of Marfan syndrome, a disorder leading to deadly aneurysms in children and adults. The 2015 recipient was Douglas R. Lowy, MD, Chief, Laboratory of Cellular Oncology (The National Cancer Institute, USA), in recognition of his discoveries that led to the development of the Human Papillomavirus vaccine to prevent cervical cancer. The 2016 recipient was Jeffrey M. Friedman, MD, PhD (The Rockefeller University, USA), for his discovery of leptin, which controls feeding behavior and is used to treat related clinical disorders. In 2017, the Prize was awarded jointly to Daniel J. Drucker, MD (Mount Sinai Hospital, Canada), Joel F. Habener, MD (Massachusetts General Hospital, USA) and Jens J. Holst, MD, DMSc (University of Copenhagen, Denmark) for their discovery of incretin hormones and for the translation of these findings into transformative therapies for major metabolic diseases such as diabetes. The 2018 recipient was Helen H. Hobbs, MD (UT Southwestern Medical Center, USA) for her discovery of the link between a gene mutation (PCSK9) and lower levels of LDL, which has improved the treatment of high cholesterol. In 2019, Dr. Carl H. June, MD, received the award for advancing the clinical application of CAR T therapy for cancer treatment, and for his sustained contributions to the field of cellular immunology.

The American Society for Clinical Investigation
Founded in 1908, the American Society for Clinical Investigation is one of the oldest and most esteemed nonprofit honor societies of physician-scientists. Membership is by election only, and only researchers who are 50 years of age or younger are eligible for nomination to the Society. Therefore, membership in the ASCI is a recognition of a researcher's significant contributions, at a relatively young age, to the understanding of human disease. The Society counts among its ranks more than 3,000 members, many of whom are leaders in academic medicine and industry. Many members have been recognized by election to the U.S. National Academy of Sciences and the U.S. National Academy of Medicine. The ASCI is also proud to have among its membership winners of the Nobel Prize and the Lasker Award. The ASCI convenes an annual meeting with the Association of American Physicians, and the Society self-publishes the prestigious Journal of Clinical Investigation (founded 1924), and JCI Insight (founded 2016).

Harrington Discovery Institute
The Harrington Discovery Institute at University Hospitals in Cleveland, OH – part of The Harrington Project for Discovery & Development – aims to advance medicine and society by enabling our nation's most inventive scientists to turn their discoveries into medicines that improve human health. The institute was created in 2012 with a $50 million founding gift from the Harrington family and instantiates the commitment they share with University Hospitals to a Vision for a 'Better World'.

The Harrington Project for Discovery & Development
The Harrington Project for Discovery & Development (The Harrington Project), founded in late February 2012 by the Harrington Family and University Hospitals of Cleveland, is a $300 million national initiative built to bridge the translational valley of death. It includes the Harrington Discovery Institute and BioMotiv, a for-profit, mission-aligned drug development company that accelerates early discovery into pharma pipelines. For more information about The Harrington Project and the Harrington Discovery Institute, visit: HarringtonDiscovery.org.

SOURCE Harrington Discovery Institute

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