Ali Nili, MD
Postdoctoral Fellowship in Drug Discovery, 2024
Dana Farber Cancer Institute
Developing New Targeted Treatment for Autoimmune Diseases
Abstract
Pemphigus vulgaris(PV) is a B-cell mediated autoimmune disease characterized by autoantibodies targeting desmoglein-3(Dsg3), a critical protein for intercellular adhesion. Available current treatments all involve immunosuppressive; a targeted therapeutic approach is needed. We developed a targeted treatment using protein engineering. This approach selectively binds to Dsg3-reactive B-cell receptors, initiating specific cytotoxicity by immune cells. The preliminary results showed the specific killing of Dsg3-autoreactive B cells by our treatment, both in vitro and in vivo. My plan includes evaluating the safety and efficacy of the treatment in active PV mouse models that will recapitulate the human PV disease. My proposed approach holds promise for PV and other autoantibody-driven diseases by specifically targeting autoreactive cells without global immunosuppression.
I am grateful for the support of the PhRMA Foundation. To me, this fellowship signifies recognition of my research in autoimmune skin diseases and offers a precious chance to further my experience in basic science that helps me to advance my career as a physician-scientist. The two years of support have granted me the opportunity to delve deeper and explore with more sophisticated insight into developing novel targeted therapies, setting the stage for clinical translation of the approach, to the benefit of many patients.
