Dr. Neal Sondheimer's research focuses on the regulation of mitochondrial gene expression and the impact of mitochondrial mutations in common and rare disease.
Strong pathogenic mitochondrial mutations exist in a state of heteroplasmy, a mixture of normal and mutated genomes. This state provides opportunities for therapy, as the increase of wild type mitochondrial DNA or the suppression of mutated mitochondrial DNA could improve health. Dr. Sondheimer and his team are investigating mechanisms that could allow shifts in heteroplasmic ratios.
Dr. Sondheimer is interested in the effects of mitochondrial mutations in common diseases and phenotypes such as Alzheimer disease, aging, autism and preterm birth. Because bioenergetic capacity is critical to many parts of the body, subtle changes in mitochondrial DNA may have profound effects over time.
The mitochondrial genome is the small, densely coding, maternally inherited DNA that encodes core subunits of the electron transport chain. Many features of gene regulation are more similar to bacterial and phage systems than they are to gene regulation in the nucleus. Defects in the maintenance of mitochondrial DNA and in the translation of gene products are known causes of disease. Dr. Sondheimer and his team are investigating the dysregulation of mitochondrial transcription as another possible avenue to bioenergetic failure.