How do macrophages integrate diverse signals to make all-or-none decisions about target cell destruction?
Research
Understanding and harnessing macrophage-mediated cell clearance in cancer and aging
Macrophages are immune cells that maintain the homeostasis of all tissues by eliminating pathogens, cancer cells, and diverse unwanted extracellular material via phagocytosis. However, in a wide range of age-related diseases, including cancer, neurodegeneration, and atherosclerosis, macrophage phagocytic capacity is suppressed, and aberrant cells, protein aggregates, and other disease-causing material accumulate. While engineered cell therapies have transformed the treatment of cancer and autoimmune disease, the therapeutic potential of macrophage phagocytosis remains largely untapped. Driven both by our curiosity about the diverse forms and functions of phagocytosis in nature and our commitment to enabling new treatments for people with incurable diseases, we aim to address the following unresolved questions:
Key Questions
What enables cancer cells to evade macrophage-mediated clearance in primary tumors and at metastatic sites?
How can macrophages be systematically engineered to eliminate a broad range of disease-causing cells and material?
Why does macrophage clearance capacity decline with age, and can it be restored?
In pursuit of these questions, we develop powerful genetic screening approaches to discover regulators of macrophage function, then apply biochemical, cell biological, and in vivo methods to dissect how they work at a mechanistic level. We are particularly drawn to genes, metabolites, and processes that have not been previously studied, which may open entirely new avenues for therapy.