
A true mentor who cares about success.
David MacPherson, PhD, serves as Professor in the Human Biology Division and Professor in the Public Health Sciences Division at Fred Hutchinson Cancer Center. He is the inaugural holder of the Vinh Bui and Tram Le Endowed Chair for Lung Cancer and a member of the Translational Data Science Integrated Research Center. Dr. MacPherson earned his PhD from the Massachusetts Institute of Technology in 2005 and his BSc honors in Biology and Pharmacology from McMaster University in 1998. Throughout his career at Fred Hutch, he has established himself as a leading researcher in cancer biology, focusing on the genetic drivers of tumorigenesis.
The MacPherson Lab investigates how mutations in specific genes cause cancer, with a particular emphasis on small-cell lung cancer, a highly aggressive neuroendocrine tumor comprising about 15% of lung cancers. Dr. MacPherson's specialty is developing preclinical models of this disease, including genetically engineered mouse models, patient-derived xenografts, and cell lines, to dissect gene functions in cancer initiation, progression, and therapy response. His team employs functional genomics approaches such as genome-scale CRISPR inactivation screens and cDNA overexpression screens, alongside genomic and transcriptomic analyses, to identify therapeutic vulnerabilities and translate discoveries into targeted treatments. These efforts address key challenges like rapid chemoresistance in SCLC patients. Landmark publications from his lab include "MAX Functions as a Tumor Suppressor and Rewires Metabolism in Small Cell Lung Cancer" (Cancer Cell, 2020), "Protein neddylation as a therapeutic target in pulmonary and extrapulmonary small cell carcinomas" (Genes & Development, 2021), "Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data" (Nature Reviews Cancer, 2019), "Crebbp Loss Drives Small Cell Lung Cancer and Increases Sensitivity to HDAC Inhibition" (Cancer Discovery, 2018), "Targeting NOTCH activation in small cell lung cancer through LSD1 inhibition" (Science Signaling, 2019), and "In vivo functional screens reveal KEAP1 loss as a driver of chemoresistance in small cell lung cancer" (Science Advances, 2025). Additional contributions encompass molecular phenotyping of SCLC subtypes via cell-free DNA (Science Advances, 2024) and insights into vulnerabilities like USP7 inhibition for restoring chemosensitivity. Dr. MacPherson also participates in the Molecular & Cellular Biology Graduate Program, training the next generation of scientists. His work has profoundly influenced SCLC research, informing strategies for precision medicine.
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