Richard M. 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
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 focuses on mechanisms by which the immune system becomes organized in stereotyped ways against discrete types of challenges. This involves the differentiation of naïve helper T cells to subsets that produce different kinds of cytokines, key effector molecules of the immune system. In turn, these different T cells subsets work with different kinds of innate cells, including neutrophils, eosinophils, macrophages and others, to mediate immunity. Properly executed, such responses mediate protection against infectious organisms or repair of damaged tissues, but, when dysregulated, these immune responses lead to disease, including asthma.
Dr. Locksley’s laboratory investigates immunity using mice genetically engineered to report cytokines expressed during allergic immune responses. This approach reveals the shared expression of important cytokines by innate and adaptive immune cells. 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.
- Locksley RM. 2010. Asthma and allergic inflammation. Cell 140:777-83.
- 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.
- 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.
- 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.
- Cheng LE, K Hartmann, A Roers, MF Krummel, RM Locksley. 2013. Perivascular mast cells dynamically probe cutaneous blood vessels to capture IgE. Immunity 38:166- 75.
- 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.
- 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.
- 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.
- 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.
- Bando JK, H-E Liang, RM Locksley. 2015. Identification and distribution of developing innate lymphoid cells in the fetal mouse intestine. Nat Immunol 16:153-160.
- 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 43:161-174.
- von Moltke J, M Ji, H-E Liang, RM Locksley. 2016. Tuft cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit. Nature 529:221-225.