Dr. Devesha Kulkarni joined the Department of Medicine as an Instructor in the Division of Gastroenterology in October, 2018.
She has over eight years of experience studying the intestinal immune cells involved in promoting tolerogenic responses towards dietary and bacterial antigens, and the effect of enteric infection on abrogation of tolerance. During her postdoctoral training with Dr. Rodney Newberry, she studied the role of intestinal goblet cell associated antigen passages (GAPs), a novel mechanism of luminal antigen delivery. She found that rapid inhibition of GAPs was critical for limiting enteric pathogen dissemination to systemic organs. Additionally, she observed that during infection, inhibition of GAP formation is critical in preventing pro-inflammatory responses directed towards innocuous antigens. In 2015, she was awarded the Crohn’s and Colitis Foundation of America (CCFA) Research Fellowship Award to elucidate the role of GAPs in promoting intestinal homeostasis. She has found that during steady-state, GAPs play a critical role in delivery of dietary antigens and antigen-specific T cell responses. Utilizing mouse models of inducible deletion of goblet cells, she observed that in the absence of GAPs, peripheral induction of regulatory T cells (Tregs) is abrogated and tolerance to dietary antigens is lost. Expanding on these observations, she has found that loss of GAPs results in a reduction of pre-existing Tregs and a rapid expansion of IL-17 producing Th-17 cells in the intestine. This suggests that GAPs play a crucial role in balancing and switching between Treg and Th-17 axis. Moreover, she discovered that the formation of GAPs can be rapidly inhibited by IL-1β, a cytokine that others have shown to be elevated in inflamed mucosa of patients with Crohn’s disease. Her current research focus extends these findings and builds upon her experience, along with the world-class resources and mentors available at Washington University School of Medicine to address the fundamental question of how balance and switching between regulatory responses and inflammatory responses are maintained at the intestinal mucosa. Knowledge gained from this research will fill the void in our understanding of balance and switch between tolerogenic and effector responses in the gut, and how loss of this balance contributes to mucosal inflammatory diseases.