From left, Paul J. Kenny, PhD; Eric J. Nestler, MD, PhD; benefactors Pamela Nash, Helen Nash, Beth Nash, and Joshua Nash, member, Mount Sinai Boards of Trustees; and Richard A. Friedman, Co-Chairman, Boards of Trustees.

It has been a time of outstanding achievement for the Icahn School of Medicine at Mount Sinai’s Department of Neuroscience—worthy of a celebration.

On Wednesday, May 8, Mount Sinai leadership, benefactors, faculty, and staff attended a reception at the Hess Center for Science and Medicine to unveil the Department’s renaming to the Nash Family Department of Neuroscience, an event held to honor the Nash family for their philanthropic generosity and extraordinary commitment to brain research.

“The Nash family has been supporting critical initiatives at Mount Sinai for more than 40 years and began a focused commitment to advance our neuroscience community more than a decade ago,” says Eric J. Nestler, MD, PhD, Nash Family Professor of Neuroscience, Director of The Friedman Brain Institute, and Dean for Academic and Scientific Affairs at the Icahn School of Medicine at Mount Sinai. “The research that has been made possible through the family’s generosity is being translated into fundamentally new and improved treatments for some of the world’s most devastating brain disorders. We are forever grateful for their commitment to this important work.”

Richard A. Friedman with guests at the reception. A substantial gift from the Friedman family allowed for the creation of The Friedman Brain Institute.

As a direct result of the Nash family’s support, Mount Sinai’s neuroscience program has seen unprecedented growth. Over the past decade, more than 40 basic neuroscience faculty have been recruited to Mount Sinai. Today, the Neuroscience department is ranked No. 1 in the nation among U.S. medical schools in National Institutes of Health (NIH) funding.

“This is testament to the incredible research environment we have created at Mount Sinai with the support of the Nash family,” says Paul J. Kenny, PhD, the Ward-Coleman Professor and Chair of the Department, and Director of Mount Sinai’s Drug Discovery Institute, who has made significant contributions to furthering the understanding of the neurobiological mechanisms of drug addiction and obesity. “With their tremendous support, we have built the depth and breadth of scientific expertise that is required for us to have a real impact in many key areas of brain research. We are translationally focused, so our work is highly relevant to human health and central nervous system disorders. We are also a very close community and we support all of our colleagues, particularly our junior scientists. We foster an environment of research excellence but also one of collaboration and support. As a result, we are second to none when it comes to research funding and scientific impact.”

Helen S. Mayberg, MD, left, with Helen Nash

Groundbreaking work in deep brain stimulation is being conducted in the newly established Nash Family Center for Advanced Circuit Therapeutics, whose founding Director, Helen S. Mayberg, MD, Mount Sinai Professor in Neurotherapeutics, and Professor of Neuroscience, Neurology, Psychiatry, and Neurosurgery, is a pioneer in using brain circuit information to treat neuropsychiatric disorders. She is leading a team to harness the potential of deep brain stimulation—an innovative surgical procedure that has proven successful in treating movement disorders—to address a range of conditions that include depression, addiction, and schizophrenia.

“Additionally, we have researchers who have deep expertise in the mechanisms of gene regulation, and those with demonstrated ability to functionally dissect, manipulate, and understand brain circuitry in the context of complex behaviors,” Dr. Kenny says. “That is where research funding is increasingly directed, and we are on the cutting edge of neurocircuitry research.”

The goal now, Dr. Kenny adds, is to bring together the Department’s key strengths in brain circuitries and mechanisms of gene expression to drive new discoveries related to brain function and its role in disease. “Given the outstanding quality of research in our Department, and the level of NIH funding we have successfully competed for, I believe Mount Sinai is positioned to have a profound impact on human brain health.”

Eric J. Nestler, MD, PhD, welcomed guests and spoke about the strengths of the Nash Family Department of Neuroscience.

Lorna Farrelly, PhD, and Ian Maze, PhD

Serotonin, a powerful chemical that sends signals between nerve cells in the brain, has long been thought to play a key role in processes such as appetite, mood, and sleep. Now, research by neuroscientists at the Icahn School of Medicine at Mount Sinai suggests that the molecule can also enter the nucleus of these cells and help turn genes on. It is a surprising discovery that has the promise to yield fundamental new knowledge about addiction, mood disorders, and neurodegenerative diseases such as Parkinson’s disease.

The findings, which were recently published in the journal Nature, are a divergence from conventional thinking that neurotransmitters have one role—which is to bind to nerve cells and send signals that change these cells’ activity.

“We have shown that there is a novel role for neurotransmitters in the brain that is independent of neurotransmission, but critically important to their overall signaling,” says Ian Maze, PhD, Assistant Professor of Neuroscience, and Pharmacological Sciences, and senior author of the multicenter study. “It suggests that our current understanding of these molecules is incomplete and requires further investigation.” Study authors also included postdoctoral fellow Lorna Farrelly, PhD.

The study involved DNA, the blueprint for all cell functions in the body. Each cell contains two strands of DNA that are packaged by histone proteins and arranged in spools known as nucleosomes. The tighter the DNA is wound into nucleosomes, the less likely that genes being encoded will be turned on, or expressed; when it is not wound as tightly, genes are more likely to be expressed.

Based on previous research that had found large pools of neurotransmitters in the nucleus of neurons and suspecting that this could result in additional, neurotransmission-independent functions for these chemicals, Dr. Maze and his team hypothesized that certain nuclear proteins may be modified by these molecules to affect their functions. They discovered that a protein, tissue Transglutaminase 2, can directly attach serotonin molecules to histone proteins, a process called histone serotonylation. Once the serotonin is attached, stronger expression of genes associated with these modified histones is observed.

They also demonstrated that these serotonyl marks on the histone protein help draw other proteins that play a key role in increasing gene expression. “We found that these marks hyper-recruit one particular factor, Transcription factor II D, that enables the genes to turn on,” Dr. Maze says. “That provides some mechanistic insight into how these marks may be influencing gene expression.”

In a blog entry summarizing these findings, Francis S. Collins, MD, PhD, the Director of the National Institutes of Health, wrote, “While much more study is needed, this is a potentially groundbreaking discovery. Not only could it have implications for managing depression and other mood disorders, it may also open new avenues for treating substance abuse and neurodegenerative diseases.”