Sharma, Rahul

Rahul  Sharma

Rahul Sharma

Primary Appointment

Assistant Professor, Medicine

Education

  • PhD, University of Delhi

Contact Information


Email: rs3wn@virginia.edu

Research Interests

Regulatory T Cell deficiency; Sjogren's syndrome; Auto-immunity.

Research Description



Regulatory T cells (Treg) exert the major mechanism of peripheral tolerance. Treg deficiency causes early mortality in mice and humans due to multi-organ autoimmune syndrome. Most, if not all, autoimmune disorders are now being attributed to either numerical deficiency or functional inefficiency of the Tregs. We study the interplay of Treg and auto-reactive T cells, in terms of their homeostasis, effector function and migration/homing to the sites of inflammation.

We have shown that IL-2 signaling plays an important role in all of these processes. For our studies, we use various mutant and knockout mice predisposed to autoimmune defects. We have developed several rapid and efficient models of Treg deficiency based abnormalities that find applications in studies on autoimmune diseases such as Allergic dermatitis, Psoriasis, Autoimmune pulmonary inflammation, Sjogren’s syndrome, Type 1 diabetes and Ulcerative colitis (Inflammatory Bowel Disease). We demonstrated that Fas/FasL pathway is a major contributor to end-organ failure during autoimmunity and that IL-2 signaling acts as a modifier of the organ specificity of the autoimmune response. Blocking these pathways lead to prolongation of lifespan through diverse mechanisms. We study the mechanisms behind the IL-2 mediated regulation of these factors with a focus on trafficking of Tregs and auto-reactive T cells.

The expression of Treg lineage transcription factor - Foxp3 is dependent on TCR signaling, IL-2 and Transforming Growth Factor-b1. Recently, we have found several novel pathways that can induce, restore or maintain Foxp3 expression independent of TCR, IL-2 and TGF-

Selected Publications