Dr. Hafler is the William S. and Lois Stiles Edgerly Professor and Chairman of the Department of Neurology at the Yale School of Medicine. He has elucidated fundamental mechanisms of T-cell autoantigen recognition and immune regulation by his investigation of human disease. His accomplishments include: the first clear generation of human autoreactive T cell clones revealing molecular mechanism for self-antigen recognition, followed by experiments elucidating the inflammatory program of autoreactive T cells in autoimmune diseases; the identification of human FoxP3 regulatory T cells and providing the first evidence of their dysfunction in autoimmune disease, linking this dysfunction to IFNg secretion. He went on to demonstrate the importance of environmental factors in inducing Treg dysregulation with the far-reaching discovery that NaCl drives both the induction of Th17 cells and IFNg in Tregs, hence linking this ubiquitous environmental factor to autoimmunity; after decades of unsuccessful attempts to decipher the genetic mechanisms of autoimmune disease, Hafler early on recognized the theoretical potential of genome wide association scans and led among the first identifications of common genetic variants in autoimmune disease. Perhaps of greater importance, he demonstrated that causal variants occur near binding sites for master regulators of immune differentiation and stimulus-dependent gene activation; in a recent landmark work, Hafler profiled the T cell state of healthy human CNS using single-cell/nucleus RNA sequencing identifying a novel mechanism for CNS immune privilege and discovering the presence of an inflammatory IFNg signature in healthy CSF T cells. He is the recent recipient of the ASAP award to investigate the role of immunity in Parkinson’s Disease. In summary, Hafler has identified fundamental mechanisms of autoimmunity through a distinctive focus on human disease, leading to novel and effective treatments. He has received many professional distinctions including: NIH Jacob Javits Scholar, Founder of the Federation of Clinical Immunology Society, ISI most cited list (H-index 132), the U of Miami Distinguished Alumni Award ,the John Dystel Prize from the AAN, ISNI McFarlin Lecture, ANA Adams Prize, and was elected into AOA, ASCI, Honorary Member of the Scandinavian Society for Immunology, the American Society of Clinical Investigation, The Association of American Physicians, and the National Academy of Medicine.
David A. Hafler, MD