My research work primarily focuses at elucidating the molecular and cellular mechanisms regulating serotonin transporter (SERT) in the intestine with a goal to understand the pathophysiological basis of IBD and diarrheal disorders associated with inflammation or enteric infections. SERT is responsible for regulating availability of extracellular serotonin via reuptake of released serotonin. Although, SERT is a well-known primary target for anti-depressant drugs; its role in the pathogenesis of various gastro-intestinal disorders and metabolic disorders is recently emerging. During the last decade, our studies utilizing a wide array of distinct and complementary approaches have characterized the function and expression of SERT in the native human intestine and provided important insights into mechanisms of its regulation. This work encompasses modulation of intestinal SERT by enteric pathogens, growth factors, epigenetic modifications and post-translational mechanisms with an overall goal to harness intestinal SERT regulatory mechanisms as a novel target for the treatment of intestinal inflammation and diarrheal disorders. Our recent studies have uncovered a novel aspect of SERT with Aryl hydrocarbon receptor (AhR) and induction of CYP1A1 (cytochrome P450 family of enzymes) in the IECs. These findings indicate that intracellular 5-HT could serve as an endogenous ligand/activator for AhR and have important relevance to IBD treatment and prevention. These studies are clinically relevant for treating Crohn’s disease and other diarrheal disorders associated with enteric infections or altered serotonin availability in the gut lumen. Our recent studies also suggested that deletion of SERT in mice given chow diet shows dysbiosis similar to what is seen in obesity. Utilizing state-of-the-art cellular and molecular approaches, we are currently identifying critical mechanisms that upregulate SERT as a novel therapeutic intervention for gut and metabolic disorders.