David Hafler, MD, FANA

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

Dr. Hafler is the William S. and Lois Stiles Edgerly Professor and Chairman Department of Neurology, Yale School of Medicine and is the Neurologist-in-Chief of the Yale-New Haven Hospital. He graduated magna cum laude in 1974 from Emory University with combined B.S. and M.Sc. degrees in biochemistry, and the University of Miami School of Medicine in 1978. He then completed his internship in internal medicine at Johns Hopkins followed by a neurology residency at Cornell Medical Center-New York Hospital in New York.

Dr. Hafler received training in immunology at the Rockefeller University then at Harvard where he joined the faculty in 1984. He was one of the Executive Directors of the Program in Immunology at Harvard Medical School and was on the faculty of the Harvard-MIT Health Science and Technology program where he was actively involved in the training of graduate students and post-doctoral fellows.

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.

Research interests
Acquired Immunodeficiency Syndrome; Genetics; HIV; Immune System; Multiple Sclerosis; Neurology; Autoimmunity
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.

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

Education
  • MD, University of Miami School of Medicine, 1978
  • BS, Emory College, 1974
  • MS, Emory University, 1974
Publications
  • Kitz A, de Marcken M, Gautron AS, Mitrovic M, Hafler DA, Dominguez-Villar M. EMBO Rep. 2016 Aug;17(8):1169-83. doi: 10.15252/embr.201541905.
  • Lowther D, Goods B, Lucca L, Lerner B, Gunel M, Love C, Hafler DA. PD-1 Marks Dysfunctional Regulatory T cells in Malignant Glioma, JCI-I, 2016;1(5):e85935. doi:10.1172/jci.insight.85935. PMCID: PMC4864991
  • Hernandez, AL, Wu C, Lowther DE, Rodriguez DM, Vudattu N, Deng S, Herold KC, Kuchroo VK, Kleinewietfeld M, Hafler DA. Sodium Chloride Inhibits Suppressive Function of Foxp3+ Regulatory T cells. J. Clin. Invest. 2015;125(11):4212-22. doi: 10.1172/JCI81151. Epub 2015 Oct 20. PubMed PMID: 26524592 JCI
  • Housley, WJ, Grutzendler J, Cotsapas C, Hafler DA Genetic variants associated with autoimmunity drive NFκB signaling and responses to inflammatory stimuli, Science Translational Medicine, Science Translational Medicine, 2015 Jun 10;7(291). PubMed PMID: 26062845
  • Cao Y, Goods BA, Raddassi K, Nepom GT, Kwok WW, Love C, Hafler DA. Functional inflammatory profiles distinguish myelin-reactive T cells from patients with multiple sclerosis. Sci Transl Med. 2015 May 13;7(287): 287ra74. doi: 10.1126/scitranslmed.aaa8038. PMID: 25972006
  • Roadmap Epigenomics Consortium. Integrative Analysis of 111 Reference Genomes.  Nature. 2015 Feb 19;518(7539):317-30. doi: 10.1038/nature14248. PMID: 25693563
  • Farh K, Marson A, Zhu J, Kleinwietfeld M, Housley WJ, Beik S, Shoresh N, Whitton H, Ryan RJH, Shishkin AA, Hatan M, Carrasco-Alfonso MJ, Mayer D, Luckey CJ, Patsopoulos NA, De Jager PL, Kuchroo VK, Epstein CB, Daly MJ, Bernstein BE, Hafler DA*. Genetic and epigenetic fine-mapping of causal variants in autoimmune disease. Nature. 2014 Oct 29. doi: 10.1038/nature13835. [Epub ahead of print] PMID: 25363779 2014
  • Stern JN, Yaari G, Vander Heiden JA Church G, Donahue WF, Hintzen RQ, Huttner AJ, Laman JD, Nagra RM, Nylander A, Pitt D, Ramanan S, Siddiqui BA, Vigneault F, Kleinstein SH, O’Connor KC, Hafler DA*. B cells populating the multiple sclerosis brain mature in the draining cervical lymph nodes. Sci Transl Med. 2014 Aug 6;6(248):248ra107. PMID: 25100741
  • Dominguez-Villar M, Gautron A, de Marcken M, Hafler DA. TLR-7 induced CD4+ T cell Anergy. Nat Immunol. 2014 Nov 17. doi: 10.1038/ni.3036. [Epub ahead of print] PubMed PMID: 25401424
  • Lozano E, Joller N, Cao Y, Kuchroo V, Hafler DA. The CD226/CD155 interaction regulates the proinflammatory (Th1/Th17) anti-inflammatory (Th2) balance in humans. J Immunol. 2013 Oct 1;191(7):3673-3680. Epub 2013 Aug 26. PMID: 23980210
  • Kleinewietfeld M, Manzel A, Titze J, Kvakan H, Yosef N, Linker RA, Muller DN, Hafler DA. Sodium chloride drives autoimmune disease by the induction of pathogenic Th17 cells. Nature. 2013 Apr 25;496(7446):518-22. PMID: 23467095
  • Dominguez-Villar M, Baecher-Allan CM, Hafler DA. Identification of T helper type 1-like, Foxp3(+) regulatory T cells in human autoimmune disease. Nat Med. 2011 Jun;17(6):673-5. Epub 2011 May 3. PMID: 21540856
  • Yang L, Anderson DE, Baecher-Allan C, Bettelli E, Oukka M, Kuchroo VK, Hafler DA, IL-21 and TGF-ß are Required for Differentiation of Human Th17 cells Nature 17;454(7202):350-2, 2008.
  • Hafler, D.A., Compston, A., Sawcer, S., Lander, S., Daly, M.J., DeJager, P.L., de Bakker, P.I.W., Gabriel, S.B., Mirel, D.B., Ivinson, A.J., Pericak-Vance, M.A., Gregory, S.G., Rioux, J.D., McCauley, J.L., Haines, J.L., Barcellos, L.F., Cree, B., Oksenberg, J.R., Hauser, S.,L. Risk alleles for multiple sclerosis identified by a genomewide study. N Engl J Med 30; 357(9):851-62, 2007.
Current projects

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.

Honors
  • John J. Dystel Prize for Multiple Sclerosis Research
  • Honorary Member
  • Most Highly Cited List in the field of Immunology
  • Raymond D. Adams Lectureship
  • Distinguished Alumni “Hall of Fame” Award
  • Best Doctors in Boston
  • The Jacobs Javits Merit Investigator Award
  • Best Doctors in America
  • Elected Member
  • Elected Member
  • Harry Weaver Scholar
  • AOA