University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Richard M. Locksley, MD

Richard M. Locksley, MD

Professor, Department of Medicine (Infectious Diseases), UCSF
Marion and Herbert Sandler Distinguished Professorship in Asthma Research, UCSF

Cancer Center Program Memberships

Affiliate Member

Research Summary

Dr. Locksley is the Director of the Sandler Asthma Basic Research Center (SABRE) and a Howard Hughes Medical Institute Investigator. He is a Professor in the Departments of Medicine and Microbiology & Immunology. He received his undergraduate degree in biochemistry from Harvard and his M.D. from the University of Rochester. After completing his residency at UCSF, he trained in infectious diseases at the University of Washington. Prior to his position as director of the SABRE Center, Dr. Locksley served 18 years as the Chief of the Division of Infectious Diseases at UCSF Medical Center. Dr. Locksley is a fellow of the American Academy of Arts and Sciences.

Dr. Locksley's laboratory addresses the immune cells and tissue responses that occur during allergic, or type 2, immunity. This includes the processes by which naïve helper T cells differentiate to become allergy-supporting Th2 cells, but also the interactions of these cells with eosinophils, basophils, mast cells and alternatively activated macrophages that mediate activities in peripheral tissues. The laboratory increasingly focuses on innate immunity, particularly since the discovery of Group 2 innate lymphoid cells, or ILC2s, which are prominently involved in allergy. Importantly, the discovery of ILC2s initiated efforts to uncover the ‘ground state’ of allergy by investigating homeostatic pathways involving these cells that might provide insights regarding their primary function in the immune system and in homeostasis.

Dr. Locksley’s laboratory pioneered the use of mice genetically engineered to report cytokines expressed during allergic immune responses. Using these methods, the laboratory participated in the discovery of innate lymphoid type 2 cells, or ILC2s, which represent a previously unknown cell now implicated in allergic immunity. The ability to study the activation and organization of innate ILC2s uncovered a role for cells associated with allergy and asthma, such as eosinophils, in processes involved with basal metabolism and tissue homeostasis. Activation of ILC2s in the small intestine was implicated in alteration of the mucosa to a secretory phenotype characterized by high numbers of goblet cells and tuft cells. The latter, a previously mysterious epithelial cell of unknown function, was shown to be the source of IL-25, a cytokine capable of activating ILC2s and other immune cells associated with allergy and asthma, thus opening up entirely new avenues for discovery.

Education

Harvard College, Cambridge, MA, B.A., 1970, Biochemistry
Univ. of Rochester, Rochester, NY, M.D., 1976, Medicine
Univ. of California, San Francisco, CA, 1976-80, Resident, Chief Resident
Univ. Wash. School of Medicine, Seattle, WA, 1980-83, Infectious Diseases


Professional Experience

  • 1986-2003
    Chief, Division of Infectious Diseases, UCSF Medical Center, San Francisco, CA
  • 1988-93
    Member and Chair (1991-93), Tropical Medicine and Parasitology Study Section, NIH
  • 1991-94
    Co-Director, Immunology Section, Biology of Parasitism Course, Woods Hole, MA
  • 1994-99
    Chair, Parasitology Pathogenesis Committee, WHO, Geneva
  • 1995-05
    Council, Chair (1998), Midwinter Conference of Immunologists, Asilomar
  • 1995-01
    Faculty, Assoc. of American Immunology Annual Course, Advanced Immunology
  • 1997-present
    Investigator, Howard Hughes Medical Institute, UCSF
  • 1998-01
    Member, Chair (2000-01), US-Japan Immunology Board, NIH
  • 2002-05
    Council, NIAID, National Institutes of Health
  • 2003-present
    Director, Strategic Asthma Basic Research Center, UCSF

Honors & Awards

  • American Society for Clinical Investigation, 1991
  • Burroughs Wellcome Fund Scholar in Molecular Parasitology, 1992-97
  • Fellow, Infectious Diseases Society of American, 1992
  • Association of American Physicians, 1994
  • Bailey K Ashford Medal, American Society Tropical Medicine and Hygiene, 1994
  • Ellison Medical Foundation Senior Scholar in Global Infectious Diseases, 2001-05
  • Distinguished Service Award, American Association of Immunologists, 2003
  • Inspirational Teacher Award, UCSF class of 2006
  • Sandler Distinguished Professorship, 2003
  • American Academy of Arts & Sciences, 2005
  • R37 MERIT Award, NIAID/NIH, 2006
  • 2017
    Member, National Academy of Sciences

Selected Publications

  1. O'Leary CE, Schneider C, Locksley RM. Tuft Cells-Systemically Dispersed Sensory Epithelia Integrating Immune and Neural Circuitry. Annu Rev Immunol. 2018 Oct 31.
    View on PubMed
  2. Ricardo-Gonzalez RR, Van Dyken SJ, Schneider C, Lee J, Nussbaum JC, Liang HE, Vaka D, Eckalbar WL, Molofsky AB, Erle DJ, Locksley RM. Tissue signals imprint ILC2 identity with anticipatory function. Nat Immunol. 2018 Sep 10.
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  3. Vivier E, Artis D, Colonna M, Diefenbach A, Di Santo JP, Eberl G, Koyasu S, Locksley RM, McKenzie ANJ, Mebius RE, Powrie F, Spits H. Innate Lymphoid Cells: 10 Years On. Cell. 2018 Aug 23; 174(5):1054-1066.
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  4. Miller CN, Proekt I, von Moltke J, Wells KL, Rajpurkar AR, Wang H, Rattay K, Khan IS, Metzger TC, Pollack JL, Fries AC, Lwin WW, Wigton EJ, Parent AV, Kyewski B, Erle DJ, Hogquist KA, Steinmetz LM, Locksley RM, Anderson MS. Thymic tuft cells promote an IL-4-enriched medulla and shape thymocyte development. Nature. 2018 Jul 18.
    View on PubMed
  5. Nadjsombati MS, McGinty JW, Lyons-Cohen MR, Jaffe JB, DiPeso L, Schneider C, Miller CN, Pollack JL, Nagana Gowda GA, Fontana MF, Erle DJ, Anderson MS, Locksley RM, Raftery D, von Moltke J. Detection of Succinate by Intestinal Tuft Cells Triggers a Type 2 Innate Immune Circuit. Immunity. 2018 Jul 17; 49(1):33-41.e7.
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  6. Nusse YM, Savage AK, Marangoni P, Rosendahl-Huber AKM, Landman TA, de Sauvage FJ, Locksley RM, Klein OD. Publisher Correction: Parasitic helminths induce fetal-like reversion in the intestinal stem cell niche. Nature. 2018 Jul 16.
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  7. Van Dyken SJ, Locksley RM. Chitins and Chitinase Activity in Airway Diseases. J Allergy Clin Immunol. 2018 Jun 27.
    View on PubMed
  8. Nusse YM, Savage AK, Marangoni P, Rosendahl-Huber AKM, Landman TA, de Sauvage FJ, Locksley RM, Klein OD. Parasitic helminths induce fetal-like reversion in the intestinal stem cell niche. Nature. 2018 Jun 27.
    View on PubMed
  9. Kotas ME, Locksley RM. Why Innate Lymphoid Cells? Immunity. 2018 Jun 19; 48(6):1081-1090.
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  10. Schneider C, O'Leary CE, von Moltke J, Liang HE, Ang QY, Turnbaugh PJ, Radhakrishnan S, Pellizzon M, Ma A, Locksley RM. A Metabolite-Triggered Tuft Cell-ILC2 Circuit Drives Small Intestinal Remodeling. Cell. 2018 May 23.
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  11. Sui P, Wiesner DL, Xu J, Zhang Y, Lee J, Van Dyken S, Lashua A, Yu C, Klein BS, Locksley RM, Deutsch G, Sun X. Pulmonary neuroendocrine cells amplify allergic asthma responses. Science. 2018 Mar 29.
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  12. Odegaard JI, Lee MW, Sogawa Y, Bertholet AM, Locksley RM, Weinberg DE, Kirichok Y, Deo RC, Chawla A. Perinatal Licensing of Thermogenesis by IL-33 and ST2. Cell. 2017 Dec 14; 171(7):1707.
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  13. Singh PB, Pua HH, Happ HC, Schneider C, von Moltke J, Locksley RM, Baumjohann D, Ansel KM. MicroRNA regulation of type 2 innate lymphoid cell homeostasis and function in allergic inflammation. J Exp Med. 2017 Dec 04; 214(12):3627-3643.
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  14. Locksley R. Turning the light on. Nat Rev Immunol. 2017 Oct; 17(10):593.
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  15. Savage AK, Liang HE, Locksley RM. The Development of Steady-State Activation Hubs between Adult LTi ILC3s and Primed Macrophages in Small Intestine. J Immunol. 2017 09 01; 199(5):1912-1922.
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  16. Lechner AJ, Driver IH, Lee J, Conroy CM, Nagle A, Locksley RM, Rock JR. Recruited Monocytes and Type 2 Immunity Promote Lung Regeneration following Pneumonectomy. Cell Stem Cell. 2017 Jul 06; 21(1):120-134.e7.
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  17. Van Dyken SJ, Liang HE, Naikawadi RP, Woodruff PG, Wolters PJ, Erle DJ, Locksley RM. Spontaneous Chitin Accumulation in Airways and Age-Related Fibrotic Lung Disease. Cell. 2017 Apr 20; 169(3):497-509.e13.
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  18. von Moltke J, O'Leary CE, Barrett NA, Kanaoka Y, Austen KF, Locksley RM. Leukotrienes provide an NFAT-dependent signal that synergizes with IL-33 to activate ILC2s. J Exp Med. 2017 Jan; 214(1):27-37.
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  19. Lee LM, Ji M, Sinha M, Dong MB, Ren X, Wang Y, Lowell CA, Ghosh S, Locksley RM, DeFranco AL. Determinants of Divergent Adaptive Immune Responses after Airway Sensitization with Ligands of Toll-Like Receptor 5 or Toll-Like Receptor 9. PLoS One. 2016; 11(12):e0167693.
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  20. Van Dyken SJ, Nussbaum JC, Lee J, Molofsky AB, Liang HE, Pollack JL, Gate RE, Haliburton GE, Ye CJ, Marson A, Erle DJ, Locksley RM. A tissue checkpoint regulates type 2 immunity. Nat Immunol. 2016 Dec; 17(12):1381-1387.
    View on PubMed

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