Research in my lab has focused on the role of mitochondria and metabolism in monogenic and complex disorders in children and adults. These disorders range from orphan diseases like Alpers and Leigh syndromes, to common diseases like autism, chronic fatigue syndrome (CFS), fibromyalgia, post-traumatic stress disorder (PTSD), depression, traumatic brain injury (TBI), chronic traumatic encephalopathy (CTE), cancer, diabetes, and autoimmune disorders, and acute and chronic infectious diseases like Lyme, malaria, and tuberculosis. We have a special interest in the molecular mechanisms of healing and tissue regeneration, innate immunity, and the interplay between genetic and environmental factors in human health and disease (Ecogenetics). My lab discovered the molecular basis of Alpers Syndrome—the oldest Mendelian form of mitochondrial disease—and we were the first to show that defects in a human DNA polymerase (the mitochondrial DNA polymerase ?, POLG) could cause human disease. We were the first to quantify the risk of neurodegeneration with infection in mitochondrial disease and the first to characterize the metabolic features of the cell danger response (CDR). My lab has developed a number of advanced technologies like biocavity laser spectroscopy, mtDNA mutation detection by mass spectrometry, and novel methods for exosome purification and analysis. We developed some of the first methods to isolate metagenomic DNA from beach sand and ocean core sediments for use in the molecular reconstruction of modern and ancient marine ecosystems. This has given us a unique window into the ecosystem biology and metabolic contributions of the gut microbiome to human health. We have developed new tools for deep phenotyping of health and disease by NextGen metabolomics and targeted mass spectrometry of samples from a wide array of biofluids, tissues, and cultured cells. These tools, along with state-of-the-art methods in mass spectrometry, stable isotope tracer studies for flux metabolomics, mitochondrial respiratory chain and polarographic analysis, permit us to dissect the metabolomic and molecular features of any disease in any cell type.

Research in my lab has focused on the role of mitochondrial DNA replication, copy number regulation, DNA damage, and nucleotide signaling in development, aging, healing and regeneration. We also study the systems biology of monogenic and complex diseases like autism and diabetes. We were the first to quantify the risk of neurodegeneration with infection in mitochondrial disease. We were also the first to show that defects in a human DNA polymerase (the mitochondrial DNA polymerase ? POLG) could cause disease. Our lab has developed a number of advanced technologies like biocavity laser spectroscopy and mtDNA mutation detection by mass spectrometry to help with rapid and early diagnosis of mitochondrial disease. Recently, we have developed new bioinformatic methods to analyze mtDNA sequence data produced by NextGen sequencing platforms like Illumina. These tools, along with state-of-the-art methods in mitochondrial respiratory chain and polarographic analysis permit us to dissect the metabolic and molecular features of virtually any disease of interest. Immediate interests include the genesis and treatment of diabetes and autism, and mutation arrest therapies for cancer and viral disease, with special attention to the crossroads of innate immunity, inflammation, somatic cell genetics, and metabolism.