Richard Locksley, 2016 BioLegend William E. Paul Awardee
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 Group2 innate lymphoid 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 aseosinophils, 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.