Robert Naviaux

Source: gordonmedical.com

Robert K. Naviaux, MD, PhD, is a Professor in Residence at the University of California, San Diego, California, USA. His work "has focused on the role of mitochondrial DNA replication, copy number regulation, DNA damage, and nucleotide signaling in development, aging, healing and regeneration in mitochondrial mechanisms of disease and development." He was invited to join the Open Medicine Foundation's research team in 2016, following a announcement that the ME/CFS Severely Ill, Big Data Study had a significant result in the area of mitochondria.

Dr. Naviaux directs the Robert Naviaux Laboratory at University of California, San Diego (UCSD) whose work is "divided into two groups: 1) Mitochondrial Mechanisms of Disease and Development, and 2) Evolutionary Systems Biology and Marine Metagenomics." He is founder and co-director of the Mitochondrial and Metabolic Disease Center at UCSD, the co-founder and a former president of the Mitochondrial Medicine Society, as well as, a founding associate editor of the journal, Mitochondrion.

Dr. Naviaux "discovered the cause and created the diagnostic test for Alpers syndrome, a mitochondrial disease... [and] is the director of the first FDA-approved clinical trial to study suramin [an antiparasitic drug] as a treatment for autism."

Currently, Dr. Naviaux is using his mitochrondria expertise, especially in metabolomics, to look for a biomarker and potential treatment for ME/CFS.

In May 2016, a study was launched, led by Dr. Naviaux and Dr. Ronald Davis, in collaboration with Dr. Eric Gordon, Dr. Paul Cheney, and the Stanford Genome Technology Center in order "to validate earlier findings of a possible diagnostic signature for ME/CFS by measuring metabolites and to evaluate the contribution of genetics to the variation in observed metabolic signatures in this disease." The initial phase, with a total of 90 participants, has been completed and suggests "the mitochondria is in hypometabolism due to a chronic cell danger response state in ME/CFS patients."

Education

• 1994-1997 - Fellowship (Biochemical Genetics, mtDNA Replication), University of California, San Diego Medical Center, San Diego, CA
• 1990-1994 - Postdoctorate (Retrovirology, Gene Therapy), The Salk Institute, La Jolla, CA
• 1986-1990 - Internship and Residency, Internal Medicine, American Board of Internal Medicine (ABIM), Clinical Investigator Pathway, University of California, Davis
• 1986, 1989 - M.D., Ph.D. (Genetics, Virology), Indiana University School of Medicine, Indianapolis, IN
• 1981 - M.S. (Zoology), Indiana University, Bloomington, IN
• 1979 - B.S. (Biological Sciences), University of California, Davis, CA
• 1977-1978 - Undergraduate (Biochemistry), Georg August Universität, Göttingen, Germany

Notable studies

• 2017, A robust, single-injection method for targeted, broad-spectrum plasma metabolomics (FULL TEXT)

  Abstract - Background: Metabolomics is a powerful emerging technology for studying the systems biology and chemistry of health and disease. Current targeted methods are often limited by the number of analytes that can be measured, and/or require multiple injections. Methods: We developed a single-injection, targeted broad-spectrum plasma metabolomic method on a SCIEX Qtrap 5500 LC-ESI-MS/MS platform. Analytical validation was conducted for the reproducibility, linearity, carryover and blood collection tube effects. The method was also clinically validated for its potential utility in the diagnosis of chronic fatigue syndrome (CFS) using a cohort of 22 males CFS and 18 age- and sex-matched controls. Results: Optimization of LC conditions and MS/MS parameters enabled the measurement of 610 key metabolites from 63 biochemical pathways and 95 stable isotope standards in a 45-minute HILIC method using a single injection without sacrificing sensitivity. The total imprecision (CVtotal) of peak area was 12% for both the control and CFS pools. The 8 metabolites selected in our previous study (PMID: 27573827) performed well in a clinical validation analysis even when the case and control samples were analyzed 1.5 years later on a different instrument by a different investigator, yielding a diagnostic accuracy of 95% (95% CI 85–100%) measured by the area under the ROC curve. Conclusions: A reliable and reproducible, broad-spectrum, targeted metabolomic method was developed, capable of measuring over 600 metabolites in plasma in a single injection. The method might be a useful tool in helping the diagnosis of CFS or other complex diseases.

• 13 Sep 2016, Metabolic features of chronic fatigue syndrome Also, see page: Metabolic features of chronic fatigue syndrome

• 7 Feb 2017, Reply to Roerink et al.: Metabolomics of chronic fatigue syndrome
• 15 Nov 2016, Reply to Vogt et al.: Metabolomics and chronic fatigue syndrome

• 2014, Metabolic features of the cell danger response (FULL TEXT)

  Abstract - The cell danger response (CDR) is the evolutionarily conserved metabolic response that protects cells and hosts from harm. It is triggered by encounters with chemical, physical, or biological threats that exceed the cellular capacity for homeostasis. The resulting metabolic mismatch between available resources and functional capacity produces a cascade of changes in cellular electron flow, oxygen consumption, redox, membrane fluidity, lipid dynamics, bioenergetics, carbon and sulfur resource allocation, protein folding and aggregation, vitamin availability, metal homeostasis, indole, pterin, 1-carbon and polyamine metabolism, and polymer formation. The first wave of danger signals consists of the release of metabolic intermediates like ATP and ADP, Krebs cycle intermediates, oxygen, and reactive oxygen species (ROS), and is sustained by purinergic signaling. After the danger has been eliminated or neutralized, a choreographed sequence of anti-inflammatory and regenerative pathways is activated to reverse the CDR and to heal. When the CDR persists abnormally, whole body metabolism and the gut microbiome are disturbed, the collective performance of multiple organ systems is impaired, behavior is changed, and chronic disease results. Metabolic memory of past stress encounters is stored in the form of altered mitochondrial and cellular macromolecule content, resulting in an increase in functional reserve capacity through a process known as mitocellular hormesis. The systemic form of the CDR, and its magnified form, the purinergic life-threat response (PLTR), are under direct control by ancient pathways in the brain that are ultimately coordinated by centers in the brainstem. Chemosensory integration of whole body metabolism occurs in the brainstem and is a prerequisite for normal brain, motor, vestibular, sensory, social, and speech development. An understanding of the CDR permits us to reframe old concepts of pathogenesis for a broad array of chronic, developmental, autoimmune, and degenerative disorders. These disorders include autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), asthma, atopy, gluten and many other food and chemical sensitivity syndromes, emphysema, Tourette's syndrome, bipolar disorder, schizophrenia, post-traumatic stress disorder (PTSD), chronic traumatic encephalopathy (CTE), traumatic brain injury (TBI), epilepsy, suicidal ideation, organ transplant biology, diabetes, kidney, liver, and heart disease, cancer, Alzheimer and Parkinson disease, and autoimmune disorders like lupus, rheumatoid arthritis, multiple sclerosis, and primary sclerosing cholangitis.

• 2008, Mitochondrial control of epigenetics
• 2004, Developing a systematic approach to the diagnosis and classification of mitochondrial disease

Awards and Honors

• 2008, Hailey’s Wish Foundation - Hailey’s Hero Award, For Outstanding Research and Clinical Care of children with mitochondrial disease
• 2007, Thomson ESI - Science Citation Index “Fast Moving Front Article”
• 2007, United Mitochondrial Disease Foundation Mitochondrial Medicine - Best Abstract Award
• 2002, Honored in a non-fiction book entitled, Anna’s Friends — Lessons Learned from a Short and Beautiful Life

Talks and interviews

• 2017, Community Symposium on the Molecular Basis of ME/CFS - 2017

Keynote Speech - "The metabolism of the cell danger response, healing, and ME/CFS"

• 2011, Youtube - "Mitochondria and Autism"

Articles

• 2016, "Mitochondria Man Gets His Money and the UK Goes Mega: Chronic Fatigue Syndrome Research Moving Forward"

Online presence

• PubMed for Robert Naviaux
• University of California, San Diego Faculty Website
• YouTube talks for Robert Naviaux on autism
• Health Rising Forum for Robert Naviaux

Learn more

• Robert Naviaux Laboratory at UC San Diego
• The Significance of Reversing Autism-Like Features in Two Distinct Mouse Models With a Single Drug, Suramin

See also

• Metabolomics
• Mitochondria
• Dauer

mitochondria Important parts of the biological cell, with each mitochondrion encased within a mitochondrial membrane. Mitochondria are best known for their role in energy production, earning them the nickname "the powerhouse of the cell". Mitochondria also participate in the detection of threats and the response to these threats. One of the responses to threats orchestrated by mitochondria is apoptosis, a cell suicide program used by cells when the threat can not be eliminated.

mitochondria Important parts of the biological cell, with each mitochondrion encased within a mitochondrial membrane. Mitochondria are best known for their role in energy production, earning them the nickname "the powerhouse of the cell". Mitochondria also participate in the detection of threats and the response to these threats. One of the responses to threats orchestrated by mitochondria is apoptosis, a cell suicide program used by cells when the threat can not be eliminated.

mitochondria Important parts of the biological cell, with each mitochondrion encased within a mitochondrial membrane. Mitochondria are best known for their role in energy production, earning them the nickname "the powerhouse of the cell". Mitochondria also participate in the detection of threats and the response to these threats. One of the responses to threats orchestrated by mitochondria is apoptosis, a cell suicide program used by cells when the threat can not be eliminated.

genome an organism's complete set of DNA, including all of its genes

metabolite A chemical compound produced by, or involved in, metabolism. The term is often used to refer to the degradation products of drugs in the body.

metabolomics The analysis of the chemical metabolism within cells, tissues or organisms. The term is often used to refer to the full set of metabolites found in a cell in a given environment.

metabolomics The analysis of the chemical metabolism within cells, tissues or organisms. The term is often used to refer to the full set of metabolites found in a cell in a given environment.

accuracy The "closeness of an observation to the true clinical state". With respect to diagnostic tests, "accuracy" means how specific and sensitive the test is.

homeostasis the maintenance of stable internal biological conditions (e.g. body temperature) in a changable environmen

membrane The word "membrane" can have different meanings in different fields of biology. In cell biology, a membrane is a layer of molecules that surround its contents. Examples of cell-biology membranes include the "cell membrane" that surrounds a cell, the "mitochondrial membranes" that form the outer layers of mitochondria, and the "viral envelope" that surrounds enveloped viruses. In anatomy or tissue biology, a membrane is a barrier formed by a layer of cells. Examples of anatomical membranes include the pleural membranes that surrounds the lungs, the pericardium which surrounds the heart, and some of the layers within the blood-brain barrier.

microbiome The full collection of microscopic organisms (especially bacteria and fungi) which are present in a particular environment, particularly inside the human body.

chronic disease a disease or condition that usually lasts for 3 months or longer and may get worse over time. Chronic diseases are long-term (typically incurable and requiring long-term management) but are not necessarily severe.

brainstem Region of the midbrain in adults, includes midbrain, pons, and medulla oblongata and develops.