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David A. Hafler, MD, FANA

William S. and Lois Stiles Edgerly Professor of Neurology and Professor of Immunobiology; Chair, Neurology; Neurologist-in-Chief, Yale New Haven Hospital

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David A. Hafler, MD, FANA

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Hafler Lab
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Research Summary

Hafler, in many respects, is credited with identifying the central mechanisms underlying the likely cause of MS. His early seminal work demonstrated that the disease began in the blood, not the brain, which eventually led to the development of Tysabri to treat the disease by blocking the movement of immune cells from the blood to the brain. He was the first to identify myelin-reactive T cells in the disease, published in Nature, showing that indeed, MS was an autoimmune disorder. He then went on to show why autoreactive T cells were dysregulated by the first identification of regulatory T cells in humans followed by demonstration of their dysfunctional state in MS. As a founding, Broad Institute member, Hafler identified the genes that cause MS, published in the New England Journal of Medicine and Nature. More recently, he identified the key transcription factors and signaling pathways associated with MS genes as potential treatment targets. Finally, he recently discovered that salt drives induction of these pathogenic myelin reactive T cells, both works published in Nature. Hafler was the Breakstone Professor of Neuroscience at Harvard, and became Chairman of Neurology at Yale in 2009, where he has built an outstanding clinical and research program that strongly integrates medical sciences. He has received numerous honors including the Dystel Prize from the AAN for his MS research and is among the most highly cited living neurologists and is a member of the National Academy of Medicine.

Specialized Terms: Neuroimmunology; Multiple Sclerosis; Autoimmunity; Genetics; Immunobiology

Extensive Research Description

Hafler is a major force in bridging basic immunology, genetics, and neurology deeply probing mechanisms to understand MS. His seminal work in 1985 demonstrating systemic immune involvement in MS (NEJM, 1985) was followed by the first identification of myelin, autoreactive T cells in MS (Nature 1990). In 2004, Hafler was the first to identify human FoxP3 regulatory T cells and then demonstrated that they are defective in MS (JEM, Nature Med, 2011). In 2001, he co-led the international effort that identified the first MS genes outside of MHC (NEJM, 2007) now with over 100 identified genes (Nature 2011). In 2009 Hafler was recruited to become Chairman of Yale Neurology and Professor of Neurology and Immunobiology where he has rapidly built an outstanding clinical program that strongly integrates medical sciences. His scientific leadership has continued where he has deeply examined the function of MS associated risk haplotypes demonstrating their significant biologic effects (JCI 2014), identified NaCl as an environmental cause of of inflammation (Nature 2013), and epigentically fine-mapped MS causal variants discovering the molecular pathways causing MS (Nature 2014). He has received innumerable professional distinctions including being becoming a Jacob Javits Scholar of the NIH, ASCI membership, the ISI most highly cited list, the University of Miami Distinguished Alumni Award and the prestigious John Dystel Prize from the American Academy of Neurology and is a member of the National Academy of Medicine.

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Research Interests

Brain Neoplasms; Multiple Sclerosis; Neurology; Neurosciences; Autoimmunity

Public Health Interests

Cancer; Genetics, Genomics, Epigenetics; HIV/AIDS; Immunology; Nutrition

Selected Publications

Clinical Trials

ConditionsStudy Title
Diseases of the Nervous SystemCognitive Training Study in Parkinson’s Disease
Diseases of the Nervous SystemEvaluating the Immune Response to COVID-19 Vaccination in B-cell Depleted Patients
COVID-19 Inpatient; COVID-19 Outpatient; Diseases of the Nervous System; HIV/AIDS; Infectious DiseasesHIV Associated Reservoirs and Comorbidities (The HARC Plus Study)
Diseases of the Nervous SystemStudy to Explore the Mechanism of Action of Ocrelizumab and B-Cell Biology in Participants With Relapsing Multiple Sclerosis (RMS)
Immune SystemImmune Response Analysis in Lymph Node Tissue
Intestinal Immunity in Neurologic Disease
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