Research

Interorganelle crosstalk between mitochondria quality control and mitosis

Mitochondria perform oxidative phosphorylation to generate ATP for a majority of the cells in the body. The accumulation of damaged or dysfunctional mitochondria contribute to a wide range of human diseases. Mitophagy is a quality control process that eliminates and recycles damaged mitochondria to prevent their accumulation. A majority of studies focus on how mitophagy defects affect post-mitotic cells because the first identified autosomal recessive mutations in mitophagy genes caused neurodegenerative diseases such as Parkinson’s. However, it is now clear that many other cell types have high levels of mitophagic activity; yet, we do not understand the importance or impact of mitophagy in these contexts. For example, stem cells display high levels of mitophagy, divide continuously throughout their lifespan, and possibly use mitophagy as a mechanism to ensure daughter cells receive healthy mitochondria. Towards this goal, our findings support that mitophagy and cell division are intimately linked by a required interorganelle signaling kinase that translocates to either mitochondria or centrosomes to activate either cell process. The broad implications of this work will elucidate why mitophagy genes are mutated in other complex diseases such as cancer, provide insight into how mitochondrial dysfunction affects stem cells contributing to neurodevelopmental and cognitive disorders, and define fundamental signaling interactions between organelles to deepen our understanding of how cells globally respond to dysfunctional mitochondria.

The role of neuroinflammation in traumatic brain injury

Traumatic brain injury (TBI) is a leading cause of death and disability, affecting millions of Americans each year. Injury occurs in two phases: (1) the initial impact, and (2) the various inflammatory processes that occur after the injury. While changes such as consistent seatbelt use and improved helmet design has helped reduce initial injury severity, relatively little progress has been made in reducing the harmful inflammation that plays a critical role in patient outcome hours to weeks after injury. We are interested in innate immunity regulatory proteins that control interferon signaling after TBI that facilitate cellular changes in the brain and contribute to inflammation. What major neurinflammatory pathways activate resident central nervous system cells like microglia and control peripheral immune cell infiltration to the contused brain? How is interferon signaling harmful to neurons after brain injury?

Funding Sources