Karuna Ganesh, MD, PhD, is a physician-scientist focused on investigating and treating metastatic gastrointestinal cancers at Memorial Sloan Kettering Cancer Center, New York, USA. She received her undergraduate and MD/PhD degrees from the University of Cambridge/MRC Laboratory of Molecular Biology, UK, where she studied mechanisms of antibody diversification with the late Professor Michael Neuberger. She trained in internal medicine at the Beth Israel Deaconess Medical Center/Harvard Medical School and in medical oncology at Memorial Sloan Kettering Cancer Center, where she completed a postdoctoral fellowship with Dr. Joan Massagué. Dr. Ganesh leads a research laboratory in the Molecular Pharmacology Program, is an Attending Physician in the Gastrointestinal Oncology Service, and Director of Metastasis Research in the Center for Colorectal Cancer at Memorial Sloan Kettering. The Ganesh laboratory employs (1) hypothesis-generation using transcriptomics, epigenomics and spatial/histological analysis of patient samples of primary and metastatic gastrointestinal (GI) cancer with (2) mechanistic dissection in cutting-edge patient-derived organoid models, including co-cultures with immune/stromal cells (3) genetically engineered and orthotopic transplantation models of metastatic GI cancer. By combining murine and clinically relevant patient-derived models, they seek to define the molecular mechanisms that underpin the phenotypic plasticity of metastatic cancer, and the co-evolution of the tumor microenvironmental response to dynamically emerging tumor regenerative states. The goal of the Ganesh laboratory is to identify crucial signaling nodes required for metastatic plasticity that can be therapeutically targeted to improve outcomes for patients with advanced cancer.