Integral to the communication between mitochondria and the nuclear DNA, adds Wallace, is the epigenome ”the totality of inherited modifications in gene expression caused by factors other than mutations in the DNA. This encompasses chemical tags that adhere to the DNA, or to the proteins that bind the DNA and regulate how genes respond to changes in the environment. "The epigenome mediates the crosstalk between nuclear DNA and mitochondrial DNA," said Wallace. "It's how the mitochondria signal the nucleus there's enough energy to grow and reproduce."

In the new Center of Mitochondrial and Epigenomic Medicine, Wallace's team is focusing on mitochondrial and epigenomic dysfunction in a wide range of clinical problems. Some common diseases they are studying include autism, epilepsy, heart disease, diabetes and obesity, forms of blindness, Alzheimer and Parkinson disease, cancer, and aging. They also are investigating how mitochondrial genes influence adaptation to extremes in our environment such as arctic cold, tropical heat, or high altitude.

Wallace's center will also focus on preclinical studies relevant to developing therapies for mitochondrial dysfunction, for which few effective clinical treatments currently exist. He will be collaborating with physician-scientists already at Children's Hospital such as Marni Falk, M.D., Neil Sondheimer, M.D., Ph.D., and Jaya Ganesh, M.D., as well as interacting with researchers in the University of Pennsylvania's Mitochondrial Research Affinity Group.

He also expects to continue working with parent advocacy groups, such as the United Mitochondrial Disease Foundation, on which he served for many years on the scientific advisory board.

"Because energy flow is central to all life processes, mitochondria play a central role throughout the life cycle," Wallace adds. "Therefore, our findings in age-related diseases help us to better understand how mitochondria dysfunction contributes to pediatric diseases, and vice-versa. Consequently, we hope to contribute to many of the excellent clinical research programs that exist throughout the outstanding clinical divisions of Children's Hospital."

Source: The Children's Hospital of Philadelphia