Joseph T. Opferman, Ph.D.

Research

White blood cells called neutrophils and macrophages are the first responders of the immune system. However, once these protective cells have obliterated their quarry, they must quickly commit suicide, so the immune system can return to normal and the body can dispose of the toxic microbial waste and damaged cells. We have established a central regulator of this balance between life and death of myeloid lineages, a gene called MCL-1. MCL-1 produces a protein that protects neutrophils against cell suicide, or apoptosis, as they mature in the bone marrow. However in macrophages, the MCL-1 protein appears to be dispensable for maturation, but instead governs the macrophages' life-and-death balance, promoting survival while the macrophage works to eliminate extracellular microbes. Using an array of genetic, biochemical and cell and molecular biological techniques, the my lab explores how MCL-1 activity is regulated in mice, and how its dysregulation contributes to malignancies and resistance to chemotherapy.