Stephen L. Hauser

Stephen L. Hauser is a professor of the Department of Neurology at the University of California, San Francisco (UCSF). His work specializes on immune mechanisms and multiple sclerosis (MS). He has contributed to the establishment of consortia that have identified more than 50 gene variants that contribute to MS risk.[1]

Stephen L. Hauser
Born (1949-12-14) December 14, 1949
New York, New York, U.S.
NationalityUnited States
Alma materHarvard Medical School
Known formultiple sclerosis research
bioethics
AwardsJohn Dystel Prize for Multiple Sclerosis Research (2008)
Charcot Award (2013)
Scientific career
FieldsNeurology, neuroimmunology
InstitutionsUniversity of California, San Francisco

Research

Hauser is a principal investigator of a large multinational effort to identify genetic effects on MS, and part of the team that identified that humoral immune mechanisms are important in the pathogenesis of MS lesions, leading to the development of B-cell based therapies for MS. He has contributed to the establishment of nationwide and international genetics consortia that have identified more than 50 gene variants that contribute to MS risk.[1]

Using comparative genomics between African-American and Caucasian MS populations, Hauser's group was able to identify HLA-DRB1 as the primary MS signal in the MHC,[2] and also fine map other secondary loci in this region.

In 2007, as a senior organizer of the International Multiple Sclerosis Genetics Consortium (IMSGC), he helped identify the first two non-HLA genes involved in MS susceptibility, IL-2R (CD25) and IL-7R (CD127).[3]

In 2010, his laboratory published the complete genome sequences and the epigenome of identical twins discordant for MS. By mid-2011 more than fifty MS associated risk alleles were identified, and by now nearly the entire array of common variants associated with MS susceptibility have now been mapped.[1]

Hauser also has focused on the role of the B cell and immunoglobulin in the pathogenesis of the disease. He developed and characterized an MS disease model that replicated the core feature of vesicular demyelination previously observed in MS, and demonstrated that this pathology resulted from the synergistic effects of autoreactive T-cells and pathogenic autoantibodies. In 1999 he published work identifying specific myelin reactivity of these autoantibodies deposited in areas of myelin damage in MS brains.[4] Hauser has translated this finding into a new potential therapy for MS. He led a large-scale clinical trial with rituximab,[5] a chimeric monoclonal antibody that depletes CD20+ B cells, and demonstrated robust efficacy in relapsing remitting MS. A second trial in primary progressive MS reported in 2009 that rituximab may similarly be effective in patients with primary progressive MS who also have evidence of ongoing inflammatory CNS disease. More recently, a third clinical trial with a fully humanized anti-CD20 monoclonal antibody, ocrelizumab, replicated the results of the rituximab trial in relapsing remitting MS.[6] With the MS Bioscreen project, Hauser has pioneered precision medicine for complex diseases like MS, creating an "actionable digital growth-chart for complex traits" [7]

Service

In 2010 Hauser was appointed to the Presidential Commission for the Study of Bioethical Issues.[8] He is a co-editor of the textbook Harrison's Principles of Internal Medicine[9] and past editor-in-chief of the Annals of Neurology.[10]

Education

Hauser trained in internal medicine at the New York Hospital-Cornell Medical Center, in neurology at the Massachusetts General Hospital (MGH), and in immunology at Harvard Medical School and the Institute Pasteur in Paris, France, and was a faculty member at Harvard Medical School before moving to UCSF.[11]

Awards and honors

Hauser received the 2013 Charcot Award from the Multiple Sclerosis International Federation,[12] the Jacob Javits Neuroscience Investigator Award,[13] and the John Dystel Prize for Multiple Sclerosis Research.[14] In 2011 he delivered the Robert Wartenberg Lecture at the American Academy of Neurology, an honor given for excellence in clinically relevant research.[15]

Hauser is the chair of the Committee on Gulf War and Health Outcomes for the Institute of Medicine[16] and a Fellow of the American Academy of Arts and Sciences and the Association of American Physicians.[17]

References
  1. The International Multiple Sclerosis Genetics Consortium & The Wellcome Trust Case Control Consortium 2; et al. (2011). "Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis". Nature. 476 (7359): 136–144. Bibcode:2011Natur.476..214T. doi:10.1038/nature10251. PMC 3182531. PMID 21833088.
  2. Jorge R. Oksenberg; et al. (2004). "Mapping multiple sclerosis susceptibility to the HLA-DR locus in African Americans". American Journal of Human Genetics. 74 (1): 160–167. doi:10.1086/380997. PMC 1181903. PMID 14669136.
  3. The International Multiple Sclerosis Genetics Consortium; et al. (2007). "Risk alleles for multiple sclerosis identified by a genomewide study". The New England Journal of Medicine. 357 (9): 851–62. doi:10.1056/NEJMoa073493. PMID 17660530. S2CID 25757453.
  4. Genain CP, Hauser SL.; Hause (2001). "Experimental allergic encephalomyelitis in the New World monkey Callithrix jacchus". Immunological Reviews. 183: 159–72. doi:10.1034/j.1600-065x.2001.1830113.x. PMID 11782255. S2CID 42786895.
  5. Hauser, SL; Waubant, E; Arnold, DL; Vollmer, T; Antel, J; Fox, RJ; Bar-Or, A; Panzara, M; Sarkar, N; Agarwal, S; Langer-Gould, A; Smith, CH; Hermes Trial, Group (2008). "B-cell depletion with rituximab in relapsing-remitting multiple sclerosis". The New England Journal of Medicine. 358 (7): 676–88. doi:10.1056/NEJMoa0706383. PMID 18272891. S2CID 38840028.
  6. Kappos, Ludwig; Li, David; Calabresi, Peter A; O'Connor, Paul; Bar-Or, Amit; Barkhof, Frederik; Yin, Ming; Leppert, David; Glanzman, Robert; Tinbergen, Jeroen; Hauser, Stephen L (2011). "Ocrelizumab in relapsing-remitting multiple sclerosis: A phase 2, randomised, placebo-controlled, multicentre trial". The Lancet. 378 (9805): 1779–87. doi:10.1016/S0140-6736(11)61649-8. PMID 22047971. S2CID 21500502.
  7. Gourraud P.-A., Henry R. G., Cree B. A. C., Crane J. C., Lizee A., Olson M. P., Santaniello A. V., Datta E., Zhu A. H., Bevan C. J., Gelfand J. M., Graves J. S., Goodin D. S., Green A. J., von Büdingen H.-C., Waubant E., Zamvil S. S., Crabtree-Hartman E., Nelson S., Baranzini S. E., Hauser S. L. (2014). "Precision medicine in chronic disease management: The multiple sclerosis BioScreen". Ann Neurol. 76 (5): 633–642. doi:10.1002/ana.24282. PMC 4214886. PMID 25263997.CS1 maint: multiple names: authors list (link)
  8. "Stephen L. Hauser, M.D." Presidential Commission for the Study of Bioethical Issues. Retrieved 2014-01-22.
  9. "Harrison's Principles of Internal Medicine, 18e". AccessMedicine. McGraw-Hill Medical. 2013-10-31. Retrieved 2014-01-22.
  10. "Annals of Neurology". Wiley Online Library. doi:10.1002/(ISSN)1531-8249. hdl:2158/1164172. Retrieved 2014-01-22. Cite journal requires |journal= (help)
  11. UCSF profile, ucsf.edu; accessed April 20, 2015.
  12. "Charcot Award". Multiple Sclerosis International Foundation. 2013-03-15. Retrieved 2014-01-23.
  13. "Stephen Hauser: Executive Profile & Biography". Bloomberg Businessweek. Bloomberg. Retrieved 2014-01-23.
  14. "John Dystel Prize". National MS Society. Retrieved 2014-01-23.
  15. "Department of Neurology: Honors and Awards". UCSF Department of Neurology. Retrieved 2014-01-23.
  16. "Stephen Hauser". Directory. Institute of Medicine. 2013-09-19. Archived from the original on 2010-04-16. Retrieved 2014-01-22.
  17. "Member Directory". Association of American Physicians. Retrieved 2014-01-23.
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