Informal Seminar - John E. Harris | Wednesday, May 8, 2024 at 4 pm

Date: Wednesday, May 8, 2024

Time: 4 pm

Location: Broad 100

Speaker: John E. Harris

Professor and Chair, Department of Dermatology

UMass Chan Medical School

Faculty Host: Long Cai

Vitiligo is a common autoimmune disease of the skin characterized by the appearance of white spots that result from the elimination of melanocytes by T cells. We determined that IFNg drives vitiligo progression through chemokines that promote T cell recruitment into the skin. Clinical trials demonstrated that JAK inhibitors that block IFNg signaling are effective treatments for vitiligo, resulting in the first FDA-approved treatment in 2022. However, treatment responses from either conventional therapies or JAK inhibitors are not durable, with relapses frequently occurring shortly after discontinuing treatment. We discovered that autoreactive resident memory T cells are responsible for disease relapse and require IL-15 for their maintenance. Targeting IL-15 signaling reverses vitiligo with long-lasting results, and a drug targeting the IL-15 receptor that we developed is in Phase 1 clinical trials, potentially representing a promising, and durable, treatment strategy for patients with vitiligo. Discovery of new signaling pathways in vitiligo using high-resolution multiomics has revealed new opportunities to develop targeted treatments. Finally, novel drug targeting strategies that we developed, including RNAi delivery, skin-tethering of bispecific antibodies, and infrared activatable antibody-drug conjugates provide exciting strategic approaches to treat this psychologically devastating disease.