Our mission is to understand how mitochondrial defects give rise to cellular dysfunction and disease. This is not an easy task, as the mitochondrion performs many essential functions, the most important being the production of most of the energy for the cell. 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 5 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 use several diverse in vitro and in vivo methods to analyze mitochondrial dysfunction. In particular, we are using the zebrafish as a model for mitochondrial diseases. The zebrafish (Danio rerio) is an important vertebrate model organism, offering many advantages for understanding basic biological processes. Breeding pairs can produce hundreds of embryos that develop outside of the mother and are frequently used in high-throughput drug screens. The use of zebrafish embryos and larvae for environmental agent testing is also well established. Furthermore, zebrafish embryos can be genetically manipulated, and because these embryos are transparent, development can be monitored and phenotypic changes can be scored easily.

There are no cures or effective long-term treatments for mitochondrial diseases. To fulfill our long-term goals of developing therapeutic treatments and new biomarkers for the early detection of mitochondrial disease, we are investigating pathways that are important in the development of mitochondrial disease, and the role of environmental and drug modifiers on mitochondrial function.

Mitochondria, mitochondrial disease, mitochondrial DNA, zebrafish, drug discovery, embryogenesis, aging, neurological disease, cardiovascular disease high-throughput in vivo methods