Arlene Helen Sharpe

Arlene H. Sharpe, M.D., Ph.D., is Kolokotrones University Professor at Harvard University and Chair of the Department of Immunology at Harvard Medical School. She serves as Vice Director of the Gene Lay Institute of Immunology and Inflammation and Leader of the Cancer Immunology Program at Dana-Farber/Harvard Cancer Center, with appointments at Brigham and Women's Hospital and the Broad Institute. Dr. Sharpe is internationally recognized for discovering and elucidating functions of T-cell costimulatory pathways, particularly the immunoinhibitory functions of the CTLA-4 and PD-1 pathways, which laid the foundation for immune checkpoint blockade therapy in cancer. In 1995, she generated CTLA-4-deficient mice, demonstrating that loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan autoimmune destruction, establishing CTLA-4's critical role in down-regulating T-cell activation and maintaining immune homeostasis. This landmark discovery, published in Immunity, revealed the essential negative regulatory function preventing uncontrolled immune responses. Sharpe subsequently characterized the PD-1 pathway. In 2001, working with Gordon Freeman (her husband and long-time collaborator), she identified PD-L2 as a second ligand for PD-1. Her laboratory demonstrated that PD-L1 and PD-L2 bind PD-1 to inhibit T-cell responses, and using PD-L1-deficient mice, showed that PD-L1 on various cell types negatively regulates T cells. Her research established that PD-L1 expression on tumors enables immune evasion, providing critical mechanistic insights for PD-1/PD-L1 blockade immunotherapy. Beyond CTLA-4 and PD-1, Sharpe systematically characterized the B7:CD28 family of costimulatory and coinhibitory molecules. Her work identifying B7-1 (CD80) and B7-2 (CD86) as ligands for CD28 and CTLA-4 provided translational insights for developing immunotherapies for cancer, autoimmune diseases, and transplant rejection. Sharpe has published over 400 papers and is a Highly Cited Researcher (top 1%, 2014-2023) and 2016 Citation Laureate. She was elected to the National Academy of Sciences and National Academy of Medicine (both 2018). Her honors include the 2025 Excellence in Immunology Award, Hamburg Award (2024), Warren Alpert Foundation Prize (2017), and William B. Coley Award (2014).

Arlene H. Sharpe博士(医学博士、哲学博士)是哈佛大学Kolokotrones大学教授和哈佛医学院免疫学系主任。她担任Gene Lay免疫与炎症研究所副主任和Dana-Farber/哈佛癌症中心癌症免疫学项目负责人,同时在Brigham and Women's医院和Broad研究所任职。 Sharpe博士因发现并阐明T细胞共刺激通路功能而享誉国际,特别是CTLA-4和PD-1通路的免疫抑制功能,这些工作为癌症免疫检查点阻断疗法奠定了基础。1995年,她生成CTLA-4缺陷小鼠,证明CTLA-4缺失导致大规模淋巴细胞增殖和致命多器官自身免疫性破坏,确立CTLA-4在下调T细胞活化和维持免疫稳态中的关键作用。这项发表于Immunity的里程碑发现揭示了预防不受控免疫反应的必要负性调节功能。 Sharpe随后表征了PD-1通路。2001年,她与Gordon Freeman(丈夫及长期合作者)合作识别PD-L2作为PD-1的第二配体。她的实验室证明PD-L1和PD-L2与PD-1结合抑制T细胞反应,并使用PD-L1缺陷小鼠显示不同细胞类型上的PD-L1负性调节T细胞。她的研究确立肿瘤上的PD-L1表达使其逃避免疫,为PD-1/PD-L1阻断免疫治疗提供了关键机制见解。 除CTLA-4和PD-1外,Sharpe系统表征了B7:CD28家族共刺激和共抑制分子。她识别B7-1 (CD80) 和B7-2 (CD86) 作为CD28和CTLA-4配体的工作为开发癌症、自身免疫疾病和移植排斥免疫治疗提供了转化见解。 Sharpe发表400+篇论文,是高被引学者(前1%, 2014-2023)和2016年引文桂冠奖获得者。2018年当选美国国家科学院和国家医学院院士。她的荣誉包括2025年免疫学卓越奖、2024年Hamburg奖、2017年Warren Alpert基金会奖和2014年William B. Coley奖。