3D rendering representing interaction between brain neurons
3D rendering representing interaction between brain neurons.

While the influence of epigenetic changes are now well known in diseases such as cancer, or Fragile X symdrome, epigenetic influences on the development of neurological or psychological disorders is less well understood. Now, in an effort to bolster this emerging research area, the Icahn School of Medicine at Mount Sinai has launched the Center for Neural Epigenome Engineering which will seek to understand how epigenomics influences the nervous system under both healthy and disease conditions.

Epigenomics is defined as molecular and chemical processes which moderate the relationship between genes and the environment that produce specific traits. These processes alter genetic activity and the structure of chromatin, the mixture of proteins and DNA that form chromosomes, without changing gene sequences. The new center will allow Mount Sinai to expand its existing neurological research in chromatin biochemistry, chemical biology, protein engineering, and single-cell “omics.”

“The application of epigenomics to neuroscience started about 20 years ago and it has revolutionized our ability to get a handle on the complex interactions between genes, the brain, and behavior,” said Eric J. Nestler, MD, PhD, director of The Friedman Brain Institute at Mount Sinai and a pioneer in the field. “The launching of the new center is a milestone moment for the field of neural epigenomics.”

The new research center will be led by Ian Maze, PhD, Howard Hughes Medical Institute (HHMI) investigator and professor of Neuroscience, and Pharmacological Sciences, at Icahn Mount Sinai. In his lab at Mount Sinai, Maze’s focus in on the interplay between chromatin regulatory mechanisms and neural plasticity in the central nervous system. The dozens of published papers to his credit include the epigenetic underpinnings of schizophrenia and the dynamics of substance abuse disorders, among others.

“At Mount Sinai, we are devoted to deciphering the nervous system’s epigenomic codes,” Maze said in a press release announcing the formation of the center. “Our hope for the Center for Neural Epigenome Engineering is that it will be a place where Mount Sinai’s neuroscientists can employ the latest epigenomic concepts and methods while working side by side with multidisciplinary experts in the field of chromatin biology. We feel this will create an environment that is currently needed to both decipher neural epigenomic codes and translate findings into potential treatments for diseases.”

Some of his earliest work in the field, spanning 20 years, was work as an undergraduate getting honeybees drunk to begin understanding how alcohol affects the brain.

“What really struck me at that time was how profoundly alcohol can change an animal’s behavior, even at times long after the booze had worn off,” said Maze. “In other words, I felt that it must be doing something more than simply temporarily altering the brain’s chemistry. That’s when I had a hunch that we should be looking at the brain’s genes for clues.”

Notable publications by the Maze lab over the past three years include articles that redefined the roles that the neurochemicals dopamine and serotonin play in the brain and how these events may contribute to cocaine and heroin addiction. Both chemicals were known to relay neural signals between cells, but Maze and his team showed that dopamine and serotonin can alter epigenetically alter long-term genetic activity by infiltrating the nucleus of neurons. Further research by his team exhibited that blocking this activity could counter the effects of cocaine and heroin addiction in rats.

“To neuroscientists, these were completely unexpected and paradigm-shifting findings,” said Paul Kenny, PhD, chair of the Nash Family Department of Neuroscience at Icahn Mount Sinai. “The results revealed a previously unrecognized and entirely new function of neurotransmitters in the brain and expanded the possibilities for how neurotransmitters modify brain function during the development of addiction.”

The new research center intends to provide additional resources to build off these findings in five specific areas of research:

  • Development of novel chemical methodologies for studying neural epigenomic phenomena in vivo;
  • Expansion of Mount Sinai’s high-throughput capacity to simultaneously study epigenomic mechanisms across diverse cell populations in the brain;
  • Employment of cutting-edge structural biology and protein engineering strategies to explore the roles that chromatin may play in the nervous system, both in healthy and diseased states;
  • Development of single-cell “multi-omics” platforms for brain-wide mapping of chromatin states; and
  • Employment of well-designed real-time experiments for assessing the roles that newly discovered epigenetic phenomena may have on neural circuits and behavior.

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