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Harvard Medical School professor Michael E. Greenberg has won the 2023 Brain Prize for his decades-long research on brain plasticity, alongside University of Cambridge professor Christine E. Holt and Max Planck Institute Director Erin M. Schuman.
The Brain Prize is the world’s largest prize in neuroscience, first awarded by the Danish Lundbeck Foundation in 2011. The 2023 prize granted around $1.45 million to three researchers, including Greenberg.
Greenberg joined HMS in 1986 and served as chair of the Department of Neurobiology from 2008 to 2022. He received a bachelor’s degree in chemistry from Wesleyan University and a Ph.D. in biochemistry from Rockefeller University.
“Together, the Brain Prize 2023 winners have made ground-breaking discoveries by showing how the synthesis of new proteins is triggered in different neuronal compartments, thereby guiding brain development and plasticity in ways that impact our behavior for a lifetime,” Richard G.M. Morris, chair of The Brain Prize selection committee, said in a press release.
Brain plasticity is the brain’s ability to adapt in response to new information throughout life, allowing the brain to function over the course of decades. Greenberg’s research centers on understanding how the brain responds to external signals and life experiences to regulate genes that make proteins required for brain plasticity.
“Mike’s elegant research highlights the power of basic discovery as the most essential fuel for scientific progress,” said HMS Dean George Q. Daley ’82. “His impressive accomplishments, which now include this wonderful accolade, show just how much is possible when researchers unwaveringly follow their curiosity and scientific passions.”
When working as a postdoctoral fellow in the lab of Edward Ziff, then a professor of biochemistry and neural science at New York University School of Medicine, Greenberg discovered that within minutes of stimulation from the outside, a mammalian cell begins expression of a gene called c-fos, which increases production of the Fos protein.
According to Greenberg, the speed of this induction indicated a possible mechanism by which nature and nurture work together to orchestrate brain plasticity.
“For many years, I’d say we encountered a lot of skepticism,” Greenberg said during a press briefing. “How could a protein acting in the nucleus affect the faraway synapses that were thought to encode the memories?”
As an assistant professor at HMS, Greenberg found a connection between neurotransmitters and changes in gene activity. He characterized a signaling cascade in which an upstream neuron’s release of neurotransmitters could cause a calcium influx and eventual gene expression change in the nucleus of a downstream neuron through activation of transcription factors like Fos.
According to Greenberg, this demonstrated that Fos functioned as a “sort of master regulator.”
“It works to turn on a complex program that includes many additional proteins that act at synapses and modify synaptic function in a myriad of ways,” Greenberg said. “I think what’s striking is that many components of this neuronal activity dependent pathway of gene regulation, when mutated, lead to development disorders of the brain.”
Greenberg’s work lends insight to the origins of developmental brain disorders where neural plasticity mechanisms are damaged, such as Rett syndrome and autism.
“I think our work and the work of many others, coupled with the possibilities for gene therapy, really give us hope for real therapeutic advance,” Greenberg said. “I’m very optimistic about this, but it requires hard work and many years of effort.”
At the press briefing, Greenberg said he would use the money to visit his fellow recipients Holt and Schuman in Europe.
“I probably will try to think of some good causes that I could devote some of the prize money to and maybe in general, a little more travel than I’ve been doing to places around the world that I haven’t been,” he added.
—Staff writer Ammy M. Yuan can be reached at email@example.com.
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