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Richard M. Locksley, M.D.

Richard Locksley, M.D. Professor, Departments of Medicine and
Microbiology & Immunology
Investigator, Howard Hughes Medical Institute

University of California, San Francisco
513 Parnassus Ave.
Medical Sciences, S-1032B, Box 0795
San Francisco, CA 94143

Tel: (415) 476-3087
Fax: (415) 502-5081

Email: richard.locksley@ucsf.edu

Locksley Lab

Cancer Center
Immunology Graduate Program
Quantitative Biosciences UCSF (QB3)
Virology and Microbial Pathogenesis
Howard Hughes Medical Institute

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.

Selected Publications:

  1. Locksley RM. 2010. Asthma and allergic inflammation. Cell 140:777-83.
  2. Price AE, HE Liang, BM Sullivan, RL Reinhardt, CJ Eisley, EJ Erle, RM Locksley. 2010. Systemically dispersed innate IL-13-expressing cells in type 2 immunity. Proc Natl Acad Sci USA 107:11489-94.
  3. Wu D, AB Molofsky, HE Liang, RR Ricardo-Gonzalez, HA Jouihan, JK Bando, A Chawla, RM Locksley. 2011. Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science 332:243-7.
  4. Liang H-E, RL Reinhardt, JK Bando, BM Sullivan, I-C Ho, RM Locksley. 2011. Divergent expression patterns of IL-4 and IL-13 define unique functions in allergic immunity. Nature Immunol 13:58-66.
  5. Molofsky AB, JC Nussbaum H-E Liang, SJ Van Dyken, LE Cheng, A Mohapatra, A Chawla, RM Locksley. 2013. Innate lymphoid type 2 cells (ILC2) sustain visceral adipose tissue eosinophils and alternatively activated macrophages. J Exp Med 210:535- 49.
  6. Nussbaum JC, SJ Van Dyken, J von Moltke, LE Cheng, A Mohapatra, AB Molofsky, EE Thornton, MF Krummel, A Chawla, H-E Liang, RM Locksley. 2013. Type 2 innate lymphoid cells control eosinophil homeostasis. Nature 502:245-8.
  7. Van Dyken SJ, A Mohapatra, JC Nussbaum, AB Molofsky, EE Thornton, SF Ziegler, ANJ McKenzie, MF Krummel, H-E Liang, RM Locksley. 2014. Chitin activates parallel immune modules that direct distinct inflammatory responses via innate lymphoid type 2 (ILC2) and γδ T cells. Immunity 40:414-24.
  8. Lee M-W, JI Odegaard, L Mukundan, Y Qui, AB Molofsky, JC Nussbaum, K Yun, RM Locksley, A Chawla. 2015. Activated type 2 innate lymphoid cells regulate beige fat biogenesis. Cell 160:74-87.
  9. Bando JK, H-E Liang, RM Locksley. 2015. Identification and distribution of developing innate lymphoid cells in the fetal mouse intestine. Nat Immunol 16:153-60.
  10. Molofsky AB, F Van Gool, H-E Liang, SJ Van Dyken, JC Nussbaum, J Lee, JA Bluestone, RM Locksley. 2015. IL-33 and IFN-γ counter-regulate group 2 innate lymphoid cell activation during immune perturbation. Immunity 43:161-74.
  11. von Moltke J, M Ji, H-E Liang, RM Locksley. 2016. Tuft cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit. Nature 529:221-25.
  12. Van Dyken SJ, JC Nussbaum, J Lee, AB Molofsky, H-E Liang, JL Pollack, RE Gate, GE Haliburton, CJ Ye, A Marson, DJ Erle, RM Locksley. 2016. A tissue checkpoint regulates type 2 immunity. Nat Immunol 17:1381-7.
  13. von Moltke J, CE O’Leary, NA Barrett, Y Kanaoka, KF Austen, RM Locksley. 2017. Leukotrienes provide an NFAT-dependent signal that synergizes with IL-33 to activate ILC2s. J Exp Med 214:27-37.