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 and member of the National Academy of 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.

Research Funding

  • April 1, 2008 - March 31, 2028 - Immune-driven Airway Epithelial Dysfunction in Muco-obstructive Asthma , Co-Investigator . Sponsor: NIH, Sponsor Award ID: U19AI077439
  • August 1, 2000 - August 31, 2027 - Biology of Infectious Diseases Training Program , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: T32AI007641
  • August 15, 2012 - July 31, 2024 - Exploring the biology of persistent type 2 airway niches in asthma , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P01HL107202
  • July 1, 1988 - April 30, 2023 - Parasite immunity orchestrated by type 2 immune cells , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01AI026918
  • July 1, 2015 - April 30, 2019 - Epithelial chitinase and lung homeostasis , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01HL128903
  • January 1, 1991 - May 31, 2018 - Initiation of allergic immunity by parasites , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01AI030663
  • July 1, 1988 - March 31, 2017 - Parasite Immunity Orchestrated by Th2 Cells , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R37AI026918
  • July 15, 2008 - June 30, 2014 - Innate immune regulation of inflammation and adaptive immunity , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P01AI078869
  • September 30, 1996 - August 31, 2006 - Interactions of Lymphocytes, Cytokines and Airway Cells , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: P50HL056385
  • September 15, 1989 - June 30, 1993 - PSYCHOLOGICAL WELL-BEING OF LABORATORY-PAIRED PRIMATES , Co-Investigator . Sponsor: NIH, Sponsor Award ID: R01RR005355
  • September 30, 1983 - August 31, 1986 - HUMAN PHAGOCYTE FUNCTION IN HEALTH AND DISEASE , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01AI019768

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

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. Wang Y, Jung H, Kim DH, Liu E, Watza D, Risma SI, Florczak KL, Kim LM, Bou Reslan Z, Gupta A, Soni R, Díaz RE, Locksley RM, Fraser JS, Lee JS, Van Dyken SJ. Humanizing acidic mammalian chitinase variants establish lung immune conditioning and control environmentally driven inflammation and fibrosis. Cell Rep. 2026 Aug 12; 45(8):117833. View on PubMed
  2. O'Keefe RN, Raghunathan K, Eissmann MF, Baloyan D, Poh AR, O'Brien M, Clapdorp E, Afshar-Sterle S, Locksley RM, Ernst M, Buchert M. Circulating inflammatory ILC2s as a biomarker of gastric cancer progression. bioRxiv. 2026 May 01. View on PubMed
  3. Touhara KK, Xu J, Castro J, Liang HE, Li G, Brizuela M, Harrington AM, Garcia-Caraballo S, O'Donnell T, Neumann D, Rossen ND, Deng F, Schober G, Li Y, Locksley RM, Brierley SM, Julius D. Parasites trigger epithelial cell crosstalk to drive gut-brain signalling. Nature. 2026 May; 653(8114):465-473. View on PubMed
  4. Sbierski-Kind J, Cautivo KM, Nilsson J, Wagner JC, Dahlgren MW, Crystal NE, McClave M, Mroz NM, Ganslmeier M, Lizama CO, Gan AL, Matatia PR, Taruselli MT, Chang AA, Caryotakis S, O'Leary CE, Kotas M, Lee JH, Gu T, Seo H, Kim HJ, Mattis AN, Peng T, Locksley RM, Molofsky AB. Type 2 lymphocytes restrict type 3 lymphocytes during liver fibrosis and colocalize in fibroblast niches. Sci Adv. 2026 Mar 13; 12(11):eaea6805. View on PubMed
  5. Liao C, Mennillo E, Kattah MG, Ji M, Wang ZE, Drucker DJ, Liang HE, Locksley RM. TSLP links intestinal nutrient sensing with amplification of the ILC2-tuft cell circuit. Nat Immunol. 2025 Dec; 26(12):2218-2226. View on PubMed
  6. Cortez VS, Viragova S, Koga S, Liu M, O'Leary CE, Ricardo-Gonzalez RR, Schroeder AW, Kochhar N, Vaka D, Boffelli D, Klein OD, Diamond MS, Liang HE, Locksley RM. IL-25-induced memory type 2 innate lymphoid cells enforce mucosal immunity. Cell. 2025 Oct 30; 188(22):6220-6235.e22. View on PubMed
  7. Sun IH, Qualls AE, Yin HS, Wang J, Arvedson MP, Germino J, Horner NK, Zhong S, Du J, Valdearcos M, Ntranos V, Locksley RM, Ricardo-Gonzalez RR, Gardner JM. RORγt eTACs mediate oral tolerance and Treg induction. J Exp Med. 2025 Aug 04; 222(8). View on PubMed
  8. Lee Y, Ishikawa T, Lee H, Lee B, Ryu C, Davila Mejia I, Kim M, Lu G, Hong Y, Feng M, Shin H, Meloche S, Locksley RM, Koltsova E, Grivennikov SI, Heiman M, Choi GB, Huh JR. Brain-wide mapping of immune receptors uncovers a neuromodulatory role of IL-17E and the receptor IL-17RB. Cell. 2025 Apr 17; 188(8):2203-2217.e17. View on PubMed
  9. Cortez VS, Viragova S, Koga S, Liu M, O'Leary CE, Ricardo-Gonzalez RR, Schroeder AW, Kochhar N, Klein OD, Diamond MS, Liang HE, Locksley RM. IL-25-induced memory ILC2s mediate long-term small intestinal adaptation. bioRxiv. 2025 Mar 29. View on PubMed
  10. Jung H, Kim DH, Díaz RE, White JM, Rucknagel S, Mosby L, Wang Y, Reddy S, Winkler ES, Hassan AO, Ying B, Diamond MS, Locksley RM, Fraser JS, Van Dyken SJ. An ILC2-chitinase circuit restores lung homeostasis after epithelial injury. Sci Immunol. 2024 10 18; 9(100):eadl2986. View on PubMed
  11. Liao C, Ji M, Wang ZE, Drucker DJ, Liang HE, Locksley RM. Telocytes link epithelial nutrient sensing with amplification of the ILC2-tuft cell circuit. bioRxiv. 2024 Oct 17. View on PubMed
  12. Schuijs MJ, Brenis Gomez CM, Bick F, Van Moorleghem J, Vanheerswynghels M, van Loo G, Beyaert R, Voehringer D, Locksley RM, Hammad H, Lambrecht BN. Interleukin-33-activated basophils promote asthma by regulating Th2 cell entry into lung tissue. J Exp Med. 2024 12 02; 221(12). View on PubMed
  13. Díaz RE, Ecker AK, Correy GJ, Asthana P, Young ID, Faust B, Thompson MC, Seiple IB, Van Dyken S, Locksley RM, Fraser JS. Structural characterization of ligand binding and pH-specific enzymatic activity of mouse Acidic Mammalian Chitinase. Elife. 2024 Jun 17; 12. View on PubMed
  14. Díaz RE, Ecker AK, Correy GJ, Asthana P, Young ID, Faust B, Thompson MC, Seiple IB, Van Dyken SJ, Locksley RM, Fraser JS. Structural characterization of ligand binding and pH-specific enzymatic activity of mouse Acidic Mammalian Chitinase. bioRxiv. 2024 Mar 25. View on PubMed
  15. Rekima A, van den Elsen L, Isnard C, Smyth DJ, Lynn MA, Yee T, Stevens NE, Machado S, Divakara N, Bhasin M, Tjiam MC, Rowel C, Servant F, Burcelin R, Locksley R, Maizels R, Lynn DJ, Egwang T, Verhasselt V. Colostrum is required for the postnatal ontogeny of small intestine innate lymphoid type 2 cells and successful anti-helminth defences. Allergy. 2024 08; 79(8):2247-2251. View on PubMed
  16. Zwick RK, Kasparek P, Palikuqi B, Viragova S, Weichselbaum L, McGinnis CS, McKinley KL, Rathnayake A, Vaka D, Nguyen V, Trentesaux C, Reyes E, Gupta AR, Gartner ZJ, Locksley RM, Gardner JM, Itzkovitz S, Boffelli D, Klein OD. Epithelial zonation along the mouse and human small intestine defines five discrete metabolic domains. Nat Cell Biol. 2024 Feb; 26(2):250-262. View on PubMed
  17. O'Keefe RN, Carli ALE, Baloyan D, Chisanga D, Shi W, Afshar-Sterle S, Eissmann MF, Poh AR, Pal B, Seillet C, Locksley RM, Ernst M, Buchert M. A tuft cell - ILC2 signaling circuit provides therapeutic targets to inhibit gastric metaplasia and tumor development. Nat Commun. 2023 10 28; 14(1):6872. View on PubMed
  18. Shaikh N, Waterhölter A, Gnirck AC, Becker M, Adamiak V, Henneken L, Wunderlich M, Hartmann W, Linnemann L, Huber TB, Krebs CF, Panzer U, Locksley RM, Wilhelm C, Breloer M, Turner JE. Retinoic acid drives intestine-specific adaptation of effector ILC2s originating from distant sites. J Exp Med. 2023 12 04; 220(12). View on PubMed
  19. Zwick RK, Kasparek P, Palikuqi B, Viragova S, Weichselbaum L, McGinnis CS, McKinley KL, Rathnayake A, Vaka D, Nguyen V, Trentesaux C, Reyes E, Gupta AR, Gartner ZJ, Locksley RM, Gardner JM, Itzkovitz S, Boffelli D, Klein OD. Epithelial zonation along the mouse and human small intestine defines five discrete metabolic domains. bioRxiv. 2023 Sep 22. View on PubMed
  20. Fahy JV, Locksley RM. Immune treatment tackles chronic obstructive pulmonary disease. Nature. 2023 09; 621(7979):476-477. View on PubMed

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