SUMMARY
Derek C. Radisky, Ph.D., is a cancer researcher who studies inductive signals from the tissue microenvironment that drive the earliest stages of breast cancer.
Dr. Radisky and his team in the Tumor Microenvironment Laboratory investigate how aging, hormones, inflammation and extracellular matrix remodeling reshape the breast into a tissue state that enables cancer to begin. Their work includes integrating spatial and single-cell profiling of human tissue with mechanistic studies in 3D organotypic cultures, donor-matched organoids and preclinical models.
A central resource for Dr. Radisky's research is an extensive cohort of women diagnosed with benign breast disease who have contributed to a living biobank of matched normal breast tissue, organoids and primary cells. This resource allows linking discoveries from intact tissue to causal testing in the laboratory.
Dr. Radisky's goal is to translate findings about this tumor microenvironment biology into practical strategies to prevent cancer, predict risk and improve outcomes for all patients.
Focus areas
Dr. Radisky has several research focus areas.
Breast cancer risk and prevention
Dr. Radisky conducts molecular, spatial and histological analyses using a cohort of more than 20,000 women diagnosed with benign breast disease at Mayo Clinic. This enables identification of the earliest tissue features that predict progression to invasive cancer. He collaborates with Mayo Clinic colleagues Amy C. Degnim, M.D., Mark E. Sherman, M.D., and Stacey J. Winham, Ph.D., to move these findings toward individualized breast cancer risk prediction and improved prevention strategies.
Lobular involution and senescence
Dr. Radisky studies how the process of age-related lobular involution becomes incomplete and contributes to postmenopausal breast cancer risk. His team is defining how cellular senescence and immune dysfunction reshape breast tissue during the aging process. The team also uses living organoid models from perimenopausal donors to test whether senolytic and immunomodulatory strategies can restore a protective tissue state.
Health differences in breast cancer
Dr. Radisky identifies microenvironment and epithelial factors in healthy-looking breast tissue to understand why breast cancer may develop or behave differently in various populations. By comparing tissue samples from carefully matched groups of people, he identifies biological differences that may affect cancer risk and aggressiveness. His goal is to find reliable markers that can help predict cancer risk and support access to care for all patients.
Microenvironment signaling as prevention targets
Dr. Radisky studies developmental and growth-factor pathways that govern epithelial plasticity and tissue remodeling in the breast. These pathways include Hedgehog and vitamin D signaling. Using donor-matched organoids and primary cells, Dr. Radisky and his team test whether medicines can be used to interrupt or reverse early changes in breast tissue that can lead to cancer.
Matrix metalloproteinases in cancer
Dr. Radisky defines the roles of matrix metalloproteinases as drivers and therapeutic targets in cancer. He collaborates with Mayo Clinic colleague Evette S. Radisky, Ph.D., to determine how these enzymes promote breast cancer and other cancers and to develop specific inhibitors with therapeutic benefit.
Spatial biology and a living tissue biobank
Dr. Radisky's laboratory develops spatial approaches, multiplex imaging, and spatial transcriptomics and proteomics. These are integrated with single-cell profiling and 3D organotypic and organoid models. These tools are anchored by a living biobank of nonmalignant breast tissue that was established in collaboration with Mayo Clinic colleague Sarah A. McLaughlin, M.D. The biobank includes matched FFPE blocks, snap-frozen tissue, organoids and primary cells from 188 donors. This enables a continuous loop from discovery in intact tissue to mechanistic testing in matched living models.
Significance to patient care
Dr. Radisky studies how breast cancer develops and grows. He looks at how different parts of the body work together, including healthy tissues, hormones, growth signals and the immune system. By learning more about these connections, he is helping develop better ways to prevent breast cancer and improve treatment options for patients.