Timothy A. Chan

Timothy A. Chan is a physician-scientist whose work has fundamentally shaped our understanding of how tumors are recognized by the immune system and how radiation therapy can be harnessed to potentiate anti-tumor immunity. At Memorial Sloan Kettering Cancer Center, where he spent the core of his scientific career, Chan led the Center for Immunotherapy and Precision Immuno-Oncology, building a laboratory program that pioneered the systematic study of neoantigens—tumor-specific mutant peptides presented to T cells—as determinants of immune checkpoint blockade response. His group was among the first to demonstrate that high tumor mutational burden (TMB) predicts clinical benefit from PD-1 blockade across multiple cancer types, work that directly contributed to the FDA approval of pembrolizumab as a tumor-agnostic therapy. In the context of radiation oncology, Chan has elucidated the mechanisms by which ionizing radiation remodels the tumor immune microenvironment, enhancing neoantigen release, type I interferon signaling, and dendritic cell activation pathways that sensitize tumors to immunotherapy. His research has provided a rigorous genomic and immunological framework for designing rational combinations of radiation and checkpoint inhibitors, moving the field beyond empirical observations of the abscopal effect toward mechanistically informed clinical trials. He has co-led multiple clinical trials at MSK testing radiation-immunotherapy combinations in lung, bladder, and melanoma. Chan's laboratory has also made major contributions to understanding how tumor microenvironment features—including HLA loss of heterozygosity, chromosomal instability, and immunoediting—shape both de novo and acquired resistance to immunotherapy. He has published landmark papers in Nature, Science, Nature Medicine, and Cell that have accumulated thousands of citations and reshaped how oncologists conceptualize the intersection of genomics, immunity, and radiation biology. He is now Chair of Radiation Oncology at Case Western Reserve University and University Hospitals Seidman Cancer Center.