For defining how T-cell costimulatory and coinhibitory molecules and pathways regulate immune responses, and for demonstrating that T cells are required not only to activate antimicrobial and antitumor immunity, but also to repress immune responses to combat tissue transplantation rejection and autoimmune disease.
An admired trailblazer in cancer research, Dr. Sharpe has defined how T-cell costimulatory and coinhibitory molecules and pathways, most notably those involving CTLA-4 and PD-1, effectively regulate immune responses. She has demonstrated that T-cells are required to not only activate and ensure antimicrobial and antitumor immunity, but also to repress immune responses in order to combat tissue transplantation rejection as well as autoimmune diseases. In a pivotal study, Dr. Sharpe generated CTLA-4 knock-out mice to evaluate the effect of CTLA-4 on T cell activation in vivo. These mice quickly developed severe autoimmune disease accompanied by in an influx of rapidly proliferating T cells, exhibiting multiorgan lymphocytic infiltration. These critical findings established CTLA-4 as a negative regulator of T cell activation.
Dr. Sharpe has also made groundbreaking discoveries to characterize the PD-1 pathway, specifically uncovering its ligands and their roles as negative regulators of PD-1. To decipher the distinct roles of these ligands in a range of immune cells, Dr. Sharpe generated PD-L1 deficient mouse models that demonstrated a clear role for PD-L1 on T cells, antigen presenting cells (APCs) and host tissues in inhibiting a T cell response. Her research has also demonstrated that PD-L1 not only interacts with CD28 and CTLA-4, but also with B7-1 to inhibit T cell activation. She continues to study coinhibitory and costimulatory pathways and is investigating the roles that PD-1 has on the immunosuppressive microenvironment of tumors. Her seminal contributions to the understanding of this pathway led to the development of pembrolizumab, a PD-1 pathway inhibitor for the treatment of several cancers. Her research has also highlighted the importance of T-cells and their co-factors in cancer and has laid the foundation for further studies involving immune checkpoint mechanisms and the development of cancer immunotherapies that have transformed the cancer field.
2020 Richard V. Smalley MD Memorial Award and Lectureship, Society for Cancer Immunotherapy
2018 Elected Member, National Academy of Medicine, Washington D.C.
2018 Elected Member, National Academy of Sciences, Washington D.C.
2017 Warren Alpert Foundation Prize
2016 Clarivate Citation Laureate, Thomson Reuters, Toronto, Canada
2015 Hall of Fame Special Recognition for Scientific Achievement, Laguna Biotech CEO Forum Award
2014-2019 Highly Cited Researcher, Thomson Reuters, Toronto, Canada
2014 William B. Coley Award for Distinguished Research in Basic and Tumor Immunology, Cancer Research Institute
2007 Elected Fellow, American Association for Advancement of Science
2006 MERIT Award, National Institutes of Health
2006 Elected Fellow, American Association for the Advancement of Science