Janitza Montalvo-Ortiz, PhD, assistant professor of psychiatry, has been awarded a grant by the National Institute on Drug Abuse (NIDA) for the project, “Deciphering the single-nucleus genomic regulatory structure of opioid use disorder in the human brain.”
Opioid use disorder (OUD) is an epidemic in the United States, associated with increased rates of hospitalization and drug overdose death. This opioid epidemic has recently worsened during the COVID-19 pandemic, as shown by a significant steep rise of up to 29.4 percent in opioid overdose deaths during 2020.
While genetic risk factors have been identified in recent large-scale genome-wide association studies (GWAS) of OUD, these explain only small fraction of the disease risk.
Epigenetic modifications, which reflects the interaction between genetic and environmental factors, have been linked to OUD, but the interplay between these modifications and its role in the human brain has yet to be refined. Specifically, how these different gene regulatory layers crosstalk in brain regions that are part of the addiction circuitry is not well understood.
Montalvo-Ortiz’s project will jointly profile methylomics, hydroxymethylomics, 3D chromatin structure, and transcriptomics of OUD in single nuclei in postmortem brains from human donors. The overall goal of the project is to obtain a better understanding of the molecular underpinnings and cell diversity of opioid use disorder in humans toward the goal of identifying molecular targets that could be used to develop new preventions and treatments.
"I want to understand that missing part that can’t be explained in a GWAS,” she said. “By expanding our knowledge on the role of epigenetics in the human brain, my hope is to bring light into the still dark tunnel of OUD’s etiology and open new avenues for treatment development to help people suffering from this disorder.”
The award budget is $300,000 direct annually for up to five years. The grant was awarded through NIDA’s Avenir Awards program, which supports early-stage investigators proposing highly innovative studies that open new areas of research for the genetics or epigenetics of addiction.