David Hafler MD, MSc

Gilbert H. Glaser Professor of Neurology and Professor of Immunobiology; Chair, Department of Neurology

Research Interests

Neuroimmunology; Multiple Sclerosis; Autoimmunity; Genetics; Immunobiology

Research Summary

Dr. Hafler’s laboratory has been a major force in defining human autoimmune disease for over a quarter of a century. After demonstrating the presence of an activated peripheral immune system in patients with MS, he was among the first to apply human T cell cloning to human disease, defining the dominant epitopes of myelin antigens in MS (Nature, 1990) and of islet antigens in diabetes (Nature 2005). His lab has deeply examined the mechanism for the loss of suppression, and was among the first to describe regulatory T cells in humans (JI, 2005) and molecular mechanism elucidating defects in regulating tolerance in autoimmune disease (JEM, 2006; Science 2007). Moreover, his lab has recently elucidated the mechanism for induction of Th17 cells in humans (Nature 2008).

He continues to be active as a clinician, and has led a number of clinical trials, including the first therapy of human autoimmune disease with monoclonal antibodies in the 1980s. After a sabbatical with Eric Lander at the Broad Institute, Hafler led the first whole genome scan identifying gene variants associated with MS (NEJM, 2007).

Dr. Hafler is Founder and past president of the Federation of Clinical Immunology Societies and is an NIH Jacob Javits Scholar.

Selected Publications

  • 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
  • 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
  • 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
  • International Multiple Sclerosis Genetics Consortium. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat Genet. 2013 Nov; 45(11):1353-60. PMID: 24076602
  • 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.
  • 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.
  • Beriou G, Ashley CW, Costantino CM, Yang L, Kuchroo VK, Baecher-Allan C, Hafler DA, IL-17 producing human peripheral regulatory T cells retain suppressive function. Blood, 2009 Apr 30;113(18):4240-9. Epub 2009 Jan 26.
  • Anderson, AC, Anderson, DE, Bregoli, L, Hastings, WD, Kassam, N, Lei, C, Chandwaskar, R, Karman, J, Su, EW, Hirashima, M, Bruce, JN, Kane, LP, Kuchroo, VK, Hafler, DA. Promotion of tissue inflammation by the immune receptor Tim-3 expressed on innate immune cells. Science 318(5853):1141-3 (2007).

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