Bingwei Lu

Mitochondrial dysfunction is commonly associated with aging and age-related chronic diseases. A major goal of our research is to understand how mitochondrial dysfunction arises during aging and contributes to the pathogenesis of a broad spectrum of age-related diseases, from cancer to neurodegenerative diseases and sarcopenia. An overarching hypothesis is that aging and age-related diseases share  fundamental molecular and cellular mechanisms. Thus, by targeting the molecular drivers of aging, we can develop new understandings and therapies for many age-related diseases. Supporting this hypothesis, our more recent studies demonstrate that reverse electron transport (RET) along mitochondrial electron transport chain is activated during aging, leading to excessive reactive oxygen species (ROS) production and imbalanced NAD+/NADH ratio, and that inhibition of RET is beneficial in disease models of brain tumors and neurodegenerative diseases. We are actively investigating the mechanism of RET activation during aging, the signaling pathways influenced by RET, and the potential of RET as a viable therapeutic target. We use Drosophila and mouse in vivo models, human induced pluropotent stem cell (iPSC) derived cell culture models, and state-of-the art techniques such as CRISPRa/i, proximity proteomics, RNA-seq, cryo-EM, and molecular dynamics simulation in our research.