Aging is the greatest risk factor for cancer, yet the molecular mechanisms by which aging dictates tumor initiation, progression, and therapeutic response remain poorly understood. Our laboratory studies how aging reshapes the cell of origin and its surrounding microenvironment to regulate cancer development and treatment response. By integrating aging, stem cell, and cancer biology, we seek to uncover fundamental principles that can be translated into new strategies for precision oncology.
How does aging reshape stem cells to influence tissue regenteration and cancer?
Aging leads to profound changes in organismal physiology, including diminished tissue regeneration and increased susceptibility to cancer. Interestingly, adult stem cells (ASCs) lie at the intersection of these two hallmarks of aging: they are the principal source of tissue regeneration throughout postnatal life and the predominant cells of origin for many cancers. We investigate how aging alters ASC function and regenerative capacity, and how these same biological changes influence malignant transformation. By identifying mechanisms that distinguish healthy regeneration from tumorigenesis, we aim to uncover therapeutic opportunities that promote tissue repair while reducing cancer risk.
Using genetically engineered mouse models (GEMMs), primary organoid cultures, and functional genomic approaches, we study stem cells under physiologically aged conditions to understand how aging influences cell fate, plasticity, and tumor susceptibility.
How does the aging tissue microenvironment shape lung cancer?
Cancer develops within a dynamic ecosystem composed of immune, stromal, vascular, and epithelial cells. Aging profoundly remodels this tissue environment, yet how these changes impact tumor initiation and progression remains largely unknown. Our laboratory investigates how the aged lung microenvironment communicates with stem cells and cancer cells to regulate cancer development.
By integrating GEMMs with single-cell, spatial, and functional approaches, we seek to define how aging reshapes cellular interactions within the lung and identify age-dependent vulnerabilities that may be leveraged for cancer prevention and therapy.
How do lung cancers respond differently to therapy with aging?
Aging is one of the most important and well-recognized risk factors for lung cancer in both smokers and never-smokers. However, older adults remain substantially underrepresented in clinical trials, limiting our understanding of how aging influences disease progression and therapeutic response. Our laboratory studies how aging changes the biology of tumors and their surrounding tissues to determine responses to targeted therapies, immunotherapies, and emerging treatment strategies.
Taking advantage of autochthonous GEMMs and organoid cultures derived from physiologically aged primary cells, we aim to faithfully recapitulate the biology of lung cancer arising in older individuals. Our goal is to establish the biological principles underlying age-specific therapeutic responses and resistance mechanisms, ultimately enabling treatment strategies that are tailored not only to the genetics of the tumor but also to the biology of aging.
Many of the most important questions in aging and cancer cannot be answered from a single perspective. Our laboratory embraces highly collaborative science that integrates expertise across stem cell biology, cancer biology, immunology, genomics, computational biology, pathology, and clinical oncology. We are fortunate to be part of the vibrant scientific community at Fred Hutchinson Cancer Center and the greater Seattle scientific ecosystem, where interdisciplinary collaboration accelerates discovery and translation. We welcome opportunities to collaborate with investigators across disciplines who share an interest in aging, regeneration, cancer, and human disease.