Naviaux, Robert

Robert K. Naviaux, MD, PhD
Professor of Medicine, Pediatrics, Pathology, and Genetics
The Mitochondrial and Metabolic Disease Center
University of California, San Diego School of Medicine
San Diego, CA
naviauxlab.ucsd.edu
biochemgen.ucsd.edu

Metabolomic Features of Chronic Illness—Lessons from Gulf War Illness and Chronic Fatigue Syndrome

Dr. Naviaux is the founder and co-director of the Mitochondrial and Metabolic Disease Center (MMDC), and Professor of Medicine, Pediatrics, Pathology, and Genetics at UCSD. He directs a core laboratory for metabolomics at UCSD. He is the co-founder and a former president of the Mitochondrial Medicine Society (MMS), and a founding associate editor of the journal Mitochondrion. He is an internationally known expert in human genetics, inborn errors of metabolism, metabolomics, and mitochondrial medicine. Dr. Naviaux is the discoverer of the cause of Alpers syndrome—the oldest Mendelian form of mitochondrial disease—and the developer of the first DNA test to diagnose it. His lab also discovered the first mitochondrial DNA (mtDNA) mutations that cause genetic forms of autism and the metabolic features of the cell danger response (CDR). He directed the first FDA-approved clinical trial to study the safety and efficacy of the antipurinergic drug suramin as a new treatment for autism spectrum disorder (ASD). His development of new methods in metabolomics showed that several complex chronic disoreders like ASD and chronic fatigue syndrome (ME/CFS) have a metabolic signature that can be used in diagnosis and lead to fresh insights to treatment.

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Conference Lecture Summary

Metabolomics has emerged as a powerful new tool in systems biology. We have collected data on over 600 natural metabolites in 8 different chronic disease cohorts by broad-spectrum, targeted metabolomics using hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS), or LC-MS/MS for short. These studies have included autism spectrum disorder (ASD), post-traumatic stress disorder (PTSD) with and without traumatic brain injury (TBI), Gulf War Illness (GWI), major depressive disorder (MDD), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), primary sclerosing cholangitis (PSC), the response to endurance and resistance exercise, and natural aging. In addition, we have studied mouse models and the developmental state known as dauer in the worm, C. elegans. These studies have shown that a diagnostic metabolic signature is present in every chronic illness studied to date, and that strong gender differences are present in each disease. All chronic illnesses that last more than about 6 months were found to express the metabolic features of a universal cellular response to environmental stress called the cell danger response (CDR). The CDR is comprised of a choreographed sequence of cellular metabolic transitions that must be completed as part of an evolutionarily conserved healing cycle. Chronic illness results when the healing cycle is blocked at different stages by abnormal metabokine signaling. Metabokines are signlaing molecules like ATP, butyrate, succinate, α-ketoglutarate, long chain fatty acids, eicosanoids, and sphingolipids that are natural products of metabolism inside of cells, but bind to specific G-protein coupled receptors (GPCRs) and ionotropic receptors outside of the cell. The relevance of these findings for post-treatment Lyme disease syndrome (PTLDS) will be discussed.