Aditi Bhargava, Ph.D.

Research Summary

The incidence of stress-related illnesses like irritable bowel syndrome and inflammatory bowel disease (IBD), have surged in the past few decades. The underlying cause of these and other stress-related diseases involves a complex interaction between genes and environment. In response to a stressor, a plethora of genes are rapidly turned "on" (activated) or "off" (repressed).

Some of these genes and their functions are known, but others remain unidentified. The long-term goal of our laboratory is to understand where these genes fit in response to a stressor and the interactions between the gut and brain in stress-related disorders. Recently, we have focused on delineating how glucocorticoids, which are released in response to a stressor, regulate gene function, and on linking molecular regulation to its physiological function.

Our recent interests focus on the regulation and function of the corticotropin-releasing factor (CRF) family of neuropeptides and their receptors, because their expression levels correlate with the degree of gastrointestinal inflammation in patients with IBD. Our hypothesis is that final inhibitory or stimulatory outcomes of gastrointestinal inflammation and motility functions depend on the differing spatial distribution (within the gastrointestinal tract) and temporal expression levels of these ligands and their receptor.

We have found that perturbations in the CRF-R2 receptor system render the mice more susceptible to sudden stress and immune challenges. We hope our research will establish how these neuropeptides help maintain a normal immune response in the gut and whether manipulation of CRF/urocortins can help ameliorate intestinal inflammation. Therapies that target this inflammatory pathway could improve the quality of life for patients with inflammatory bowel diseases and decrease the lifetime cost of treatment.