Major Research Projects
Nuclear Control of Mitochondrial Gene Expression
This project involves:
- the characterization of human mitochondrial transcription factors and complexes in vivo and in vitro
- characterization of the functional significance of the direct binding of mitochondrial ribosomal protein L12 to the mitochondrial RNA polymerase (POLRMT)
- the role of mitochondrial 12S rRNA methylation in maternally inherited deafness (due to the A1555G mtDNA mutation)
- generation of mouse gene knock-outs to probe in vivo functions, tissue-specific pathology and environmental exacerbation associated with loss of mtDNA regulation
Mitochondrial Dysfunction and Oxidative Stress in Ataxia-Telangiectasia (A-T)
We have shown that disrupted ATM signaling results in aberrant expression of RNR subunits, improperly regulated mtDNA copy number, increased mtDNA mutagenesis, and ROS accumulation, leading us to hypothesize that mitochondrial dysfunction contributes to the oxidative stress-associated pathology of A-T. This project will dissect mechanistically how disruptions in this pathway affect mitochondrial function in cultured cell and mouse models of the disease, with the goal of identifying potential new therapeutic strategies for A-T pathology.
The Role of the Target of Rapamycin (TOR) Pathway in Regulating Mitochondrial Gene Expression, Respiration, and Life Span
Here we are exploiting the budding yeast genetic model system to understand how reduced TOR signaling extends yeast chronological lifespan, which we have shown involves alterations in mitochondria function and ROS signaling.
Mitochondrial Genomic Instability and ROS signaling in Tumorigenesis
Mouse models of cancer are being studies in genetic backgrounds with enhanced mtDNA instability, compromise mitochondria function, or alter ROS signaling events