Research Team Receives NIH Grant for Study of Epigenetic Processes in Alcoholism

The National Institutes of Health has awarded the research team of Claes Wahlestedt, M.D., Ph.D., Associate Dean and Director of the Center for Therapeutic Innovation at the Miller School of Medicine, a $1.725 million, five-year grant to study epigenetic mechanisms that underlie alcoholism. The research could lead to new treatments for this prevalent and debilitating disorder.

Excessive alcohol consumption costs the United States more than $200 billion a year. According to the Centers for Disease Control and Prevention, about 17 million adults in the United States have been diagnosed with an alcohol use disorder and despite treatment efforts, more than 80 percent experience relapse. Long-term changes in brain function underlie these pathological drinking behaviors

The new studies funded by the NIH grant will help determine the mechanisms by which epigenetic enzymes reprogram the brain for alcohol dependence.

“Our research will help scientists and clinicians better understand the changes in the brain that cause alcohol abuse,” said Wahlestedt, professor and Vice Chair of Psychiatry and Behavioral Sciences and principal investigator of the project. “Further, the recent development of drugs that target epigenetic processes lends hope that the signaling pathways we identify can lead to new treatments for this often devastating disorder.”

Epigenetics is the study of the biological mechanisms that switch genes on and off, under the influence of external factors. Epigenetic processes are believed to cause changes in brain function by integrating genetic risk factors with life experience, explained Wahlestedt.

“Because alcohol use disorder (alcoholism) is a highly complex disease that develops as a result of both genetic predispositions and life experiences such as stress, we believe that epigenetic processes in the brain could underlie abnormal drinking behaviors.”

Wahlestedt is an internationally recognized researcher of basic epigenetic mechanisms as well as of novel drug therapies. In previous studies Wahlestedt and his collaborators have identified several epigenetic signaling pathways that change in the brain as a consequence of consuming alcohol. Other studies have found that these same epigenetic processes cause inflammation in parts of the brain.

“Inflammation is the body’s way to protect itself from harmful stimuli,” Wahlestedt said. “However, in extreme cases, like chronic alcohol consumption, too much inflammation actually contributes to the problem,” he said. “Our proposed studies will explicitly test whether the epigenetic pathways we have identified regulate inflammation in alcoholism, and whether these processes contribute to excessive drinking.”

The project, titled “Epigenetic Signaling Pathways Contributing to Alcohol Dependence,” is led by a team of scientists from the Center for Therapeutic Innovation at the University of Miami, including co-investigators Andrea Johnstone, Ph.D., a neuroscientist and postdoctoral researcher, and Shaun Brothers, Ph.D., a pharmacologist and research assistant professor, in the Department of Psychiatry and Behavioral Sciences; and Bohdan Khomtchouk, a Ph.D. student and bioinformatician.

The research is a collaborative effort with Co-Principal Investigator Markus Heilig, M.D., Ph.D., a world-renowned expert in addiction research and the director of the new Centre for Translational Psychiatric Research at Linköping University in Sweden.

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