Synthia Mellon, PhD

Recall Professor
Department of Obstetrics Gynecology & Reproductive Sciences
Research Overview: 

Our laboratory studies the regulation of steroid hormone synthesis, by analyzing the transcriptional regulation of the steroidogenic enzymes, and the mechanism of action of steroids in both steroidogenic tissues and in the nervous system, where we identified the developmental and regional expression of steroidogenic enzymes and some novel actions of steroids on neuronal function. Steroid hormones are regulators of a multitude of physiologic processes, and act primarily by activating nuclear receptors, which are transcriptional regulators of various genes. However in the nervous system, where we found steroidogenic enzymes and synthesis of a novel class of steroid, called neurosteroids, neurosteroids modulate ion flux through the ion gated GABA A and NMDA receptors, and regulation of their synthesis results in changes in behavior, learning, and memory. We delineated the ontogeny and sites of steroidogenic enzyme expression , and showed that neurosteroids affect neuronal development by specifically modulating either axonal or dendritic growth and neuronal differentiation.Their actions throughout life may maintain the integrity of neural connections, and demise of neurosteroid synthesis may result in loss of memory associated with some age-related neurologic diseases. Our studies thus rely on a number of different experimental paradigms, from molecular biologic analysis of gene structure and transcription factors to developmental and cell biology of neuronal development and function.

Primary Thematic Area: 
Developmental & Stem Cell Biology
Secondary Thematic Area: 
Neurobiology
Research Summary: 
Developmental Regulation, Molecular Biology and Novel Actions of Steroid/Neurosteroid Synthesis
Publications: 

Circulating cell-free mitochondrial DNA levels and glucocorticoid sensitivity in a cohort of male veterans with and without combat-related PTSD.

Translational psychiatry

Blalock ZN, Wu GWY, Lindqvist D, Trumpff C, Flory JD, Lin J, Reus VI, Rampersaud R, Hammamieh R, Gautam A, SBPBC, Doyle FJ, Marmar CR, Jett M, Yehuda R, Wolkowitz OM, Mellon SH

Integrated analysis of proteomics, epigenomics and metabolomics data revealed divergent pathway activation patterns in the recent versus chronic post-traumatic stress disorder.

Brain, behavior, and immunity

Muhie S, Gautam A, Misganaw B, Yang R, Mellon SH, Hoke A, Flory J, Daigle B, Swift K, PTSD Systems Biology Consortium, Hood L, Doyle FJ, Wolkowitz OM, Marmar CR, Ressler K, Yehuda R, Hammamieh R, Jett M

Shorter telomere length predicts poor antidepressant response and poorer cardiometabolic indices in major depression.

Scientific reports

Rampersaud R, Wu GWY, Reus VI, Lin J, Blackburn EH, Epel ES, Hough CM, Mellon SH, Wolkowitz OM

Molecular signatures of post-traumatic stress disorder in war-zone-exposed veteran and active-duty soldiers.

Cell reports. Medicine

Muhie S, Gautam A, Yang R, Misganaw B, Daigle BJ, Mellon SH, Flory JD, Abu-Amara D, Lee I, Wang K, Rampersaud R, PTSD Systems Biology Consortium, Hood L, Yehuda R, Marmar CR, Wolkowitz OM, Ressler KJ, Doyle FJ, Hammamieh R, Jett M

The Genetic Basis for the Increased Prevalence of Metabolic Syndrome among Post-Traumatic Stress Disorder Patients.

International journal of molecular sciences

Misganaw B, Yang R, Gautam A, Muhie S, Mellon SH, Wolkowitz OM, Ressler KJ, Doyle FJ, Marmar CR, Jett M, Hammamieh R