The main focus of our research is to define the role of mitochondrial biology in cancer and understand the molecular basis of therapeutic resistance in multiple types of cancer including in prostate, pancreatic, breast, and colon cancers. We are working on several interconnected and complementary research projects. The first project delineates how mitochondria-mediated cell death signaling is defective in cancer cells and cancer stem cells. The second project defines the role of mitochondrial unfolded protein response in cancer progression and the development of therapeutic resistance in patients with cancer. The third project characterizes the role of mitochondria in cancer health disparities among Americans. We also investigate the role of mitochondrial dysfunction in age-related neurodegenerative diseases and drug abuse. Our research suggests that deregulation of protein complexes contributes to tumor progression and therapeutic resistance in cancer. We use multiple biochemical, genetic, cellular, mouse models of cancer, clinical, and molecular approaches to identify and characterize protein complexes in subcellular compartments including in mitochondria. We envision that a detailed understanding of protein complexes will lay a foundation for targeting cell death and survival machineries for better therapeutic outcomes in patients with cancer. Our ultimate goals are to understand the mitochondrial biology and identify novel targets for prevention and therapy of multiple types of cancer as well as for other age-related diseases.