Miller School Faculty Awarded $1.7 Million to Study Non-Coding RNA Mediated Epigenetic Regulation

Mohammad A. Faghihi, M.D., Ph.D., assistant professor of psychiatry and behavioral sciences at the Center for Therapeutic Innovation, has been awarded a $1.7 million five-year grant by the National Institute of Neurological Disorders and Stroke to study epigenetic regulation of brain-derived neurotrophic factor (BDNF), an important nerve growth factor found in the brain and periphery. BDNF supports the survival of existing neurons, and encourages the growth and differentiation of new neurons and synapses.

With his grant for “Antisense RNA Mediated Epigenetic Regulation of Brain Derived Neurotrophic Factor,” Faghihi will study how long non-coding antisense RNAs, which are endogenous regulatory elements frequently transcribed in the human genome, mediate alteration of epigenetic marks to suppress the expression of sense mRNA and protein.

Faghihi also will examine the role of non-coding RNAs as epigenetic modulators of BDNF expression to explain the molecular mechanisms behind antisense RNA-induced chromatin modifications. He also hopes to establish novel non-coding RNA therapeutic targets for several neuropsychological disorders, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis — commonly known as Lou Gehrig’s disease — Rett syndrome and major depression.

“Although there is no doubt left about widespread expression of non-coding RNAs, the mechanisms of their function and involvement in human diseases remained mainly in the realm of conjecture,” Faghihi said. “In this study and based on our long-term experience in the field, we hypothesize that non-coding RNA-driven epigenetic mechanisms will play a major role in gene expression.”

Co-investigators on the grant include Juan Young, Ph.D., assistant professor of human genetics, and Marco Magistri, Ph.D., assistant scientist in the Department of Psychiatry and Behavioral Sciences.

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