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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

Website:
Locksley Lab

Programs:
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. He is a member of the Pew Scholars Program Advisory Committee and the Lasker Basic Medical Research Awards Jury. Dr. Locksley is an elected member of the American Academy of Arts and Sciences and 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, and tuft cells, enigmatic epithelial cells of mucosal surfaces which activate tissue ILC2s and neural regulatory circuits, thus opening up entirely new avenues for discovery.

Selected Publications:

  1. Locksley RM. 2010. Asthma and allergic inflammation. Cell 140:777-83.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. Lechner AJ, IH Driver, J Lee, CM Conroy, A Nagle, RM Locksley, JR Rock. 2017. Recruited monocytes and type 2 immunity promote lung regeneration following pneumonectomy. Cell Stem Cell 21:120-134
  8. Van Dyken SJ, H-E Liang, R Naikawadi, P Woodruff, P Wolters, D Erle, RM Locksley. 2017. Spontaneous chitin accumulation in airways and age-related fibrotic lung disease. Cell 169:497-509.
  9. Sui P, DL Wiesner, X Jinhao, Y Zhang, J Lee, SJ Van Dyken, A Iashua, C Yu, BS Klein, RM Locksley, G Deutsch, X Sun. 2018. Pulmonary neuroendocrine cells amplify allergic asthma responses. Science 360: eean8546. DOI: 10.1126/science.aan8546.
  10. Miller CN, I Proekt, J von Moltke, KL Wells, AR Rajpurkar, H Wang, K Rattay, IS Khan, TC Metzger, JL Pollack, AC Fries, WW Lwin, EJ Wigton, AV Parent, B Kyewski, DJ Erle, KA Hogquist, LM Steinmetz, RM Locksley, MS Anderson. 2018. Thymic tuft cells promote an IL-4-enriched medullary microenvironment and shape thymocyte development. Nature (in press).
  11. Schneider C, CE O’Leary, J von Moltke, H-E Liang, Q Yan Ang, PJ Turnbaugh, S Radhakrishnan, Michael Pellizzon, A Ma, RM Locksley. 2018. A metabolite-triggered tuft cell-ILC2 circuit drives small intestinal remodeling. Cell 174:271-284.
  12. Kotas ME, RM Locksley. 2018. Why ILCs? Immunity 48:1081-1090.
  13. Nadjsombati MS, JW McGinty, MR Lyons-Cohen, JB Jaffe, L DiPeso, C Schneider, CN Miller, JL Pollack, GA Nagana Gowda, DJ Erle, MS Anderson, RM Locksley, D Raftery, J von Moltke. 2018. Detection of succinate by intestinal tuft cells triggers a type 2 innate immune circuit. Immunity 49:33-41.
  14. Vivier E, D Artis, M Colonna, A Diefenbach, JP Di Santo, G Eberl, S Koyasu, RM Locksley, ANJ McKenzie, RF Mebius, F Powrie, H Spits. 2018. Innate lymphoid cells: ten years on. Cell (in press).
  15. Ricardo-Gonzalez RR, SJ Van Dyken, C Schneider, J Lee, JC Nussbaum, H-E Liang, D Vaka, WL Eckalbar, AB Molofsky, DJ Erle, RM Locksley. 2018. Tissue signals imprint ILC2 identity with anticipatory function. Nature Immunol (in press).