Stuart Orkin receives $500,000 Gruber Genetics Prize for his groundbreaking research on the genetics of inherited blood disorders
March 02, 2021
The 2021 Gruber Genetics Prize recognizes
hematologist-oncologist and geneticist Stuart H. Orkin, MD, of Dana-Farber/Boston
Children’s Cancer and Blood Disorders Center, for his pioneering discoveries of
the genetic underpinnings of blood disorders. His remarkable body of work has
not only revolutionized our understanding of how these illnesses occur but has
also 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. Dr. Orkin is the David G. Nathan Distinguished Professor of
Pediatrics at Harvard Medical School and an Investigator of the Howard Hughes
Medical Institute.
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.
“Dr. Orkin has led the field of hematology for more
than 40 years,” says Eric Olson, professor at UT Southwestern and member
of the Selection Advisory Board. “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, an
inherited blood disorder characterized by inadequate production of the protein
beta-globin, one of two chains of hemoglobin, the oxygen-carrying component of
red 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 time a laboratory technique
known as “positional cloning” was used 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 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 that occurs around the
time of birth, thus solving 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 reactivates expression of fetal hemoglobin and
eliminates the signs of sickle cell disease. These stunning findings have led
to the development of exciting 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,” says Aravinda Chakravarti,
professor at New York University School of Medicine and member of the Selection
Advisory Board. “It’s a great honor to be awarding the Gruber Genetics Prize to
such an extraordinary scientist.”
The Genetics Prize is presented to a leading
scientist, or up to three, in recognition of groundbreaking contributions to
any realm of genetics research.
Laureates of the Gruber Genetics Prize:
- 2020: Bonnie Bassler, for pioneering
discoveries on bacterial communication
- 2019: Bert Vogelstein, for discoveries of
new genetic pathways and processes contributing to cancer
- 2018: Joanne Chory and Elliot
Meyerowitz, for helping revolutionize plant molecular biology, with
implications for global agriculture, the environment, and human health and
disease
- 2017: Stephen Elledge, for discovering and
characterizing the molecular mechanisms of the DNA damage response pathway
in eukaryotic cells
- 2016: Michael Grunstein and David
Allis, for the discovery of the role of histone proteins and their
covalent modification in the regulation of eukaryotic gene expression
- 2015: Emmanuelle Charpentier and Jennifer
Doudna, for establishing a framework for universal genome editing
- 2014: Victor Ambros, David Baulcombe, and Gary
Ruvkun, for pioneering the study of small non-coding RNAs, molecules
that are recognized as playing a critical role in regulating gene
expression
- 2013: Svante Pääbo, for pioneering the
analysis of ancient DNA
- 2012: Douglas C. Wallace, for his
groundbreaking contributions to mitochondrial genetics
- 2011: Ronald Davis, for pioneering
development and application of recombinant-DNA techniques
- 2010: Gerald Fink, whose work in yeast
genetics advanced the field of molecular genetics
- 2009: Janet Davison Rowley, for her
seminal discoveries in molecular oncology
- 2008: Allan C. Spradling, for his work on
fly genomics
- 2007: Maynard V. Olson, for his
contributions to genome science
- 2006: Elizabeth H. Blackburn, for studies
of telomeres and telomerase, and her science advocacy
- 2005: Robert H. Waterston, for his
pivotal role in the Human Genome Project
- 2004: Mary-Claire King, for three major
findings in modern genetics: the similarity of the human and chimpanzee genomes,
finding a gene that predisposes to breast cancer and forensic genetics.
- 2003: David Botstein, a driving force in
modern genetics who established the ground rules for human genetic mapping
- 2002: H. Robert Horvitz, who defined
genetic pathways responsible for programmed cell death
- 2001: Rudolf Jaenisch, who created the
first transgenic mouse to study human disease
The Prize recipients are chosen by the Genetics
Selection Advisory Board. Its members are: Marlene Belfort, University at Albany, SUNY; Aravinda
Chakravarti, New York University, School of Medicine; Philip Hieter,
Michael Smith Laboratories at the University of British Columbia; Jeannie T.
Lee, Harvard Medical School; James Lupski, Baylor College of Medicine; Eric N.
Olson, The University of Texas Southwestern Medical Center; and Allan Spradling,
Carnegie Institution for Science (Chair).
About the Gruber
International Prize Program
The Gruber International Prize Program honors
individuals in the fields of cosmology, genetics, and neuroscience, whose
groundbreaking work provides new models that inspire and enable fundamental
shifts in knowledge and culture. The Selection Advisory Boards choose
individuals whose contributions in their respective fields advance our
knowledge and potentially have a profound impact on our lives. The
Genetics Society of America partners with the Foundation on the Genetics Prize and nominates the members of the Genetics Selection Advisory Board. For more
information on the Gruber Prizes, visit www.gruber.yale.edu.