"The proper study of mankind is man."
Large-scale epigenomics in human cohorts
To paraphrase Pope's statement, understanding diseases that afflict the mankind requires the study of humans themselves. However, humans are exposed to countless and often uncontrollable environmental stimuli, including day-to-day life stressors, that can affect the epigenome in subtle and complex ways. To disentangle such complexity with the highest precision possible, the Zannas Lab at the University of North Carolina at Chapel Hill conducts large-scale epigenomic analyses in human cohorts that have extensive information on stress exposure and disease outcomes. Participating cohorts include the longitudinal AURORA (Advancing Understanding of RecOvery afteR traumA) study and the long-term national Women's Health Initiative (WHI). These analyses are implemented through collaborations of our lab with UNC principal investigators Dr. Samuel A. McLean (AURORA) and Dr. Eric Whitsel (WHI).
Mechanistic investigations in cellular models
While analyzing human cohorts is a requisite for understanding stress-related disorders, gaining deeper insights into the underlying epigenetic mechanisms also necessitates the use of well-controlled molecular experiments. Our lab employs innovative approaches to model certain aspects of both stress exposure and aging-related disease states, such as replicative senescence and inflammation, in culture. These approaches include the exposure of relevant human cells, for example fibroblasts and immune cells, to glucocorticoid stress hormones. Despite the limitations inherent to using cells as reductionist models of disease states, we believe that such mechanistic cell work, in combination with convergent analyses in human cohorts, can greatly advance the way we conceptualize stress-related diseases.
Cross-species translation of stress epigenetics
We further aim to extend and translate the insights gained from our studies in humans with the use of rodent models that enable experimental manipulations of living organisms exposed to stress. This aim is accomplished through collaborations with UNC principal investigator Dr. Jose Rodriguez-Romaguera. Furthermore, our lab is one of the core sites of the Carolina Stress Initiative, a translational initiative of the UNC Department of Psychiatry that aims to unravel how dysfunctional brain circuits and related epigenetic changes lead to trauma and stress-related diseases. The ultimate goal is to translate our findings into novel interventions for patients suffering from these devastating diseases.