Aditi Bhargava, PhD

Associate Professor
Department of Surgery
UCSF Center for the Neurobiology of Digestive Diseases
Aditi.Bhargava@ucsfmedctr.org

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.

Primary Thematic Area: 
Tissue / Organ Biology & Endocrinology
Secondary Thematic Area: 
Neurobiology
Research Summary: 
Gut-brain cross-talk: mediation by stress hormone system

Websites

Publications: 

Enriched environment and stress exposure influence splenic B lymphocyte composition.

PloS one

Gurfein BT, Hasdemir B, Milush JM, Touma C, Palme R, Nixon DF, Darcel N, Hecht FM, Bhargava A

Actin Cytoskeleton-Dependent Regulation of Corticotropin-releasing Factor Receptor Heteromers.

Molecular biology of the cell

Hasdemir B, Mahajan S, Oses-Prieto J, Chand S, Woolley M, Burlingame A, Grammatopoulos DK, Bhargava A

One-time injection of AAV8 encoding urocortin 2 provides long-term resolution of insulin resistance.

JCI insight

Gao MH, Giamouridis D, Lai NC, Walenta E, Paschoal VA, Kim YC, Miyanohara A, Guo T, Liao M, Liu L, Tan Z, Ciaraldi TP, Schenk S, Bhargava A, Oh DY, Hammond HK

Sex- and corticotropin-releasing factor receptor 2- dependent actions of urocortin 1 during inflammation.

American journal of physiology. Regulatory, integrative and comparative physiology

Hasdemir B, Mhaske P, Paruthiyil S, Garnett EA, Heyman MB, Matloubian M, Bhargava A