Biosketch
Arlene Sharpe is an immunologist recognized for her work on T cell costimulation. She is known particularly for her studies that have defined the functions of B7-1, B7-2, CTLA-4, and PD-1 and its ligands PD-L1 and PD-L2, which has provided critical translational insights that have unpinned the development of immunotherapies for cancer, autoimmune diseases and transplant rejection. Sharpe was born and raised in Gary, Indiana. She graduated from Harvard University, Cambridge Massachusetts with an A.B. in Biochemistry and Molecular Biology, from Harvard University with a Ph.D. in Microbiology and Molecular Genetics in 1981 and from Harvard Medical School with an M.D. in 1982, followed by a residency in pathology at Brigham and Women’s Hospital. She was a postdoctoral fellow at the Whitehead Institute and joined the faculty at Harvard Medical School in 1992. She was listed by Thomas Reuters as one of the most Highly Cited Researchers in 2014, 2015 and 2017, and as a 2016 Citation Laureate. She received the William B. Coley Award for Distinguished Research in Tumor immunology in 2014 and the Warren Alpert Foundation Prize in 2017 for her contributions to the discovery of the PD-1 pathway. She has been president of the American Association of Immunologists and is a member of the National Academy of Sciences.
Research Interests
Arlene Sharpe's laboratory is interested in regulation of immune responses and has studied T cell costimulatory and immune checkpoint inhibition molecules. They have used genetic approaches to define the functions of T cell costimulatory and checkpoint inhibitory pathways in mice. Their work led to the discovery of B7-2, and comparative studies of B7-1 and B7-2 revealed that B7-2 is the major early activating costimulator for initiating immune responses. Their studies with CTLA-4 deficient mice demonstrated the critical inhibitory function of CTLA-4 and its role in T cell tolerance. Her laboratory also identified PD-L1 and PD-L2 as ligands for PD-1, thereby defining the PD-1 pathway and identifying the drug target, and showed that both of these PD-1 ligands can inhibit T cell responses in collaboration with Gordon Freeman. Further in vivo work demonstrated the roles of PD-L1 in promoting T cell tolerance and resolution of inflammation. In collaboration studies with Rafi Ahmed and Gordon Freeman, her laboratory discovered that the PD-1:PD-L1 pathway contributes directly to T cell exhaustion and lack of viral control during chronic LCMV infection. Additional studies demonstrated that PD-L1 is highly expressed on many human tumors, and allows these tumors to inhibit immune attack.
Membership Type
Member
Election Year
2018
Primary Section
Section 43: Immunology and Inflammation