Two Harvard Medical School scientists have received prizes from the Gruber Foundation.
Christopher A. Walsh, the Bullard Professor of Pediatrics and Neurology at Harvard Medical School and Boston Children’s Hospital, will share the 2021 Gruber Neuroscience Prize with Christine Petit of the Institut Pasteur and Collège de France for their groundbreaking work in revealing the genetic and molecular mechanisms behind inherited neurodevelopmental disorders.
Walsh, who is an investigator of the Howard Hughes Medical Institute, is receiving the award for his novel and fundamental insights into the development of the cerebral cortex and into the molecular origins of brain disorders, including inherited forms of epilepsy and autism spectrum disorders. Petit is receiving the award for her seminal contributions to the understanding of the mechanisms involved in hearing and hearing loss.
Read more about Walsh and the Gruber Neuroscience Prize
“These remarkable scientists have had a profound impact on our understanding of how the brain functions, both in health and disease,” said Frances Jensen, co-director of the Penn Medicine Translational Neuroscience Center, Perelman School of Medicine, University of Pennsylvania, and chair of the selection advisory board for the prize. “Their research has also led to the development of exciting and promising new genetic therapies for neurodevelopmental disorders.”
While working separately in the 1990s, Petit and Walsh pioneered an innovative approach to identify the genes responsible for hereditary hearing loss and disorders of the cerebral cortex: They studied the genomes of geographically isolated consanguineous families with multigenerational histories of such conditions. Then, using animal models and laboratory techniques created in their own laboratories, they went on to describe how the expression of these genes affects either the brain’s processing of sound or the formation of the cerebral cortex.
“Drs. Petit and Walsh’s visionary genetic studies of inherited brain disorders have illuminated how the human brain develops,” said Carla Shatz, the Sapp Family Provostial Professor of Neurobiology and Biology and the Catherine Holman Johnson Director of Stanford Bio-X and a member of the selection advisory board for the prize. “It is wonderful to recognize their contributions with this prestigious award.”
The Gruber Neuroscience Prize, which includes a $500,000 award, will be presented to Petit and Walsh in November at the annual meeting of the Society for Neuroscience.
Stuart Orkin, the David G. Nathan Distinguished Professor of Pediatrics at HMS and Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, has received the 2021 Gruber Genetics Prize, for his pioneering discoveries of the genetic underpinnings of blood disorders. Orkin is also an investigator of the Howard Hughes Medical Institute.
A hematologist‐oncologist and geneticist, Orkin’s remarkable body of work has not only revolutionized our understanding of how hematologic disorders arise but has led to promising new gene-based therapies for thalassemia and sickle cell disease, two inherited blood disorders that affect millions of people around the world.
Read more about Orkin and the Gruber Genetics Prize
“Dr. Orkin has led the field of hematology for more than 40 years,” said Eric Olson, professor at the University of Texas Southwestern Medical Center and a member of the selection advisory board for the prize. “His work has been deeply mechanistic, groundbreaking, and impactful. Through a series of seminal discoveries, he has helped to unravel key molecular mysteries behind how blood cells develop—and how inherited blood disorders occur.”
Early in his career, Orkin identified many genetic mutations behind the various types of thalassemia, a disorder characterized by inadequate production of the protein beta-globin, one of two chains of hemoglobin, the oxygen-carrying component of red blood cells. This ambitious undertaking led to the creation of the first comprehensive genetic “catalogue” of a human molecular disease. Orkin also identified the gene that causes another inherited blood disorder, chronic granulomatous disease. This discovery marked the first use of a technique known as “positional cloning” to identify a gene responsible for a human disease.
Orkin then went on to isolate and characterize GATA1, a master regulator of all genes in developing red blood cells and the founding member of a family of GATA proteins directing differentiation of cells in many tissues. More recently, Orkin’s laboratory identified the gene BCL11A that controls the switch between fetal and adult hemoglobin, which occurs around the time of birth. The discovery solved a hematologic enigma that had long evaded scientists. Orkin and his team demonstrated that turning off BCL11A interferes with the silencing of fetal hemoglobin. Inactivating BCL11A in adult genetically engineered mice reactivated expression of fetal hemoglobin and eliminated signs of sickle cell disease, this work also demonstrated. These findings have led to the development of new gene-based therapies for beta-thalassemia and sickle cell disease—therapies that have already shown clinical promise.
“Thanks to Dr. Orkin’s insights, elegant experiments, and tenacity, we are on the cusp of making major therapeutic breakthroughs for several inherited hematologic disorders,” said Aravinda Chakravarti, professor at New York University School of Medicine and a member of the selection advisory board for the prize. “It’s a great honor to be awarding the Gruber Genetics Prize to such an extraordinary scientist.”
The prize, which includes a $500,000 award, will be presented to Orkin at the annual meeting of the American Society of Human Genetics in October.
