The research program is aimed at utilizing the new tools of genomics and computational biology to understand mitochondrial biology and metabolism. We are particularly interested in the rare mitochondrial disorders – collectively the largest class of inborn errors of metabolism. Major efforts in the group are aimed at identifying all of the protein components of mitochondria, discovering the regulatory networks that control their expression and assembly, and discovering genetic variants that disrupt these proteins and networks in human disease. We have found that an elevated NADH/NAD+ ratio, or reductive stress, is an important driver of mitochondrial disease. Ongoing work is aimed at targeting this parameter. Some of our work has implications for type 2 diabetes.