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SC COBRE in Oxidants, Redox Balance, and Stress Signaling

Sherine Chan, Ph.D.

Sherine Chan, Ph.D.
Assistant Professor
Pharmaceutical and Biomedical Sciences

Ph.D., University of Western Australia 2002

The role of mitochondrial DNA stability in the development of mitochondrial diseases

Our mission is to understand how mitochondrial defects early in life give rise to cellular dysfunction and disease. Defects in any of the approximately 1,500 mitochondrial proteins can lead to pathological states such as neurodegeneration and cancer. In addition to genetic defects, mitochondrial dysfunction can arise from contact with many environmental agents and drug treatments. Mitochondria contain multiple copies of their own small, circular genome (mitochondrial DNA, mtDNA). Recently, investigators reported that 1 in 200 healthy humans harbor a pathogenic mtDNA mutation. Further complicating the understanding of mitochondrial diseases are issues related to mtDNA copy number in different tissues and different cellular states, levels of mtDNA mutations within cells (known as heteroplasmy), tissue differences in mitochondrial needs, and wide variability in disease presentation and onset of disease despite the same disease mutation. We are developing zebrafish (Danio rerio) models of mtDNA instability. Basic biochemical (in vitro) studies need to be complemented by in vivo animal models to provide information on why mutations in mitochondrial disease loci give rise to such a wide spectrum of disease phenotypes with different ages of onset and different tissue specificities, even with the same disease mutation. I hypothesize that these differences in disease outcome are due to modulation of developmental processes by environmental exposures early in life.


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