Michael Grunstein, a distinguished professor of biological chemistry at the David Geffen School of Medicine at UCLA, has been awarded the 2018 Albert Lasker Basic Medical Research Award for his groundbreaking research on gene expression. He shares the award with C. David Allis of Rockefeller University in New York.
Grunstein provided the first demonstration that histones — the proteins that package DNA within chromosomes — are more than inert structures that serve simply as spools for DNA. Working with his team at UCLA, he showed via experiments with yeast that histones actually play an important role in gene expression.
That expression — often described as the turning "on" or "off" of genes — is crucial to the development of every aspect of the body. A greater understanding of histones’ role in this process has provided a deeper insight into both normal and abnormal development. Because abnormal development can lead to diseases and other health disorders, the discovery created new avenues for research and treatment.
"As dean of the David Geffen School of Medicine and a colleague of Michael's for the past 20 years, it is both a personal and professional honor to see his scientific creativity and unwavering pursuit of new biological insights recognized by the Lasker committee," said Dr. Kelsey Martin, dean of the Geffen School of Medicine. “His pioneering work fundamentally changed our understanding of one of the most basic aspects of biology — the regulation of which genes are turned on and off in each cell — and opened the door for new therapeutic approaches to disease."
Born in Romania to Holocaust survivors, Grunstein moved to Montreal, Canada, as a child. He earned an undergraduate degree from McGill University in Montreal and a PhD from the University of Edinburgh in Scotland. He did his postdoctoral training at Stanford University in Palo Alto, California, where he invented the colony hybridization screening technique of recombinant DNAs in the lab of David Hogness, an influential biochemist, geneticist and developmental biologist laboratory.
Soon after coming to UCLA in 1975, Grunstein and his team pioneered the genetic analysis of histones in yeast, showing for the first time that histones are regulators of gene activity in living cells. They also showed that the presence or absence of a particular chemical group, known as an acetyl, at certain spots within histones helps turns the genes on and off.
Allis, with whom Grunstein shares the award, discovered that an established gene co-activator can add acetyl groups to histones and that this modification is crucial for efficient gene expression. His findings sealed the connection between histone modifications and genetic regulation.
"Professor Grunstein has been a valued member of our UCLA community for 43 years, and we are extremely proud of his paradigm-shifting work and the impact it has had in advancing the frontiers of medicine," said Dr. John Mazziotta, vice chancellor of UCLA Health Sciences and CEO of UCLA Health.
The Lasker Awards, widely regarded as America's top biomedical research prize, will be presented Sept. 21 in New York by the Lasker Foundation. The organization seeks to increase support for biomedical research by celebrating the power of biomedical science to save and improve human lives.
The foundation's statement announcing this year's winners read, in part: "With these awards, we honor innovative scientific thinking and years of dedicated meticulous research that expanded knowledge and improved health. These researchers made groundbreaking discoveries, but not all at once. Their achievements came piece by piece, with each step depending upon continued funding and societal support."
Referring specifically to Grunstein and Allis, the foundation said the scientists revealed a previously hidden layer of gene control that contributes meaningfully to biological processes. Because of their work, it said, researchers have discovered that errors in histone modifications contribute to several developmental disorders and various forms of cancer, providing new targets for potential therapies.