Basic Biology of Mitochondria and mtDNA
Most of the projects in the lab have their genesis in understanding basic mechanisms of mitochondrial function elucidated through studies in yeast, mice, and cultured mammalian cells. This includes a long-standing interest in understanding expression and maintenance of mtDNA (transcription, RNA processing, translation, replication, and repair) and the delineation of mitochondria-to-nucleus (i.e. retrograde) stress-signaling pathways involving reactive oxygen species (ROS) and other signals.
Mitochondria in Disease.
We are actively studying how mitochondria are involved in neurodegenerative diseases and cancer. This includes how mitochondrial ROS and metabolism are involved in ataxia-telangiectasia and Alzheimer’s disease, and how alterations in mitochondrial signaling contribute to tumorigenesis, chemotherapy and immunotherapy responses.
Mitochondria in Aging.
Following from our yeast studies on mTORC1 signaling in aging, we are characterizing tissue-specific responses to mitochondrial oxidative stress in mammals. Our hypothesis is that specific types and durations of mitochondrial stress instigate mitohormesis (beneficial, anti-aging signaling).
Mitochondria in Immunity.
Because mitochondria are derived from ancient bacteria, they maintain molecular features that can activate the human immune system. We discovered that mtDNA can gain access to the cytoplasm and activate anti-viral, innate immune signaling pathways. We are characterizing how mtDNA is released and the cellular consequences of this novel form of mitochondrial stress signaling and their involvement in human diseases, aging and immune system activation.