Cell death, neurodegenerative disease and mitochondrial quality control.

One of our goals is to understand the genetic and molecular mechanisms that regulate cell death, neurodegeneration, and cancer. Much of our work on neurodegeneration, particularly as it relates to defects in mitochondrial function, Alzheimer’s disease and Parkinsons disease, occurs in collaboration with the lab of Ming Guo, MD, PhD, a practicing Neurologist and researcher at UCLA. Expression from the mitochondrial genome (mtDNA) is required in almost all cells for respiration. Mutant mtDNA accumulates during adulthood and contributes to many diseases of aging, including Alzheimer’s, Parkinsons, diabetes and muscle wasting. We are particularly interested in devising methods for selectively removing damaged mtDNA. We have developed a model of mtDNA mutation accumulation in muscle and are using this system to identify molecules that can promote the selective removal of mutant mtDNA, a form of quality control. In other work we have extended the system to the nervous system. In short, our goal is to engineer mtDNA “housecleaning” during adulthood. Our recently published results indicate that we can promote the removal of ~80% of mutant mtDNA in Drosophila muscle. We are, naturally, interested in expanding this work into human systems, and drug screens.