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.