Robert K. Naviaux

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Robert K. Naviaux

MD, PhD
Born
Robert Keith Naviaux

(1956-06-27)June 27, 1956
Woodland, California, U.S.
NationalityAmerican
CitizenshipUnited States of America
Education
  • BS
  • MA
  • MD
  • PhD in human genetics and virology
Alma mater
  • Georg August University, Göttingen, Germany
  • University of California, Davis
  • Indiana University
Known forDiscovery of the cause of Alpers syndrome, Metabolic features of the cell danger response (CDR), Mitochondrial and metabolic features and stages of the healing cycle (salugenesis), Co-founder of the Mitochondrial Medicine Society (MMS), Hyperpurinergia hypothesis for the genesis and treatment of autism
Spouse(s)Jane Crowley Naviaux
Children2
Awards
  • Inaugural Kelsey Wright Award, UMDF (2001)
  • Autism trailblazer award, Autism Speaks (2011)
  • Lifetime achievement award, MMS (2018)
  • Pioneering achievement award, ISEAI (2019)
Scientific career
FieldsMitochondrial medicine, molecular and medical genetics, biochemical genetics, inborn errors of metabolism, metabolomics, virology, immunology, ecosystem biology, environmental medicine
InstitutionsUC San Diego
ThesisConstruction and characterization of three infectious molecular clones of encephalomyocarditis virus (1989)
Doctoral advisorW. Dean Fraser, Milton W. Taylor, M. Ed Hodes, Joe C. Christian, George W. Jordan, Stuart H. Cohen
Websitenaviauxlab.ucsd.edu

Robert K. Naviaux (born in 1956) is an American physician-scientist and thought leader in the field of mitochondrial medicine and complex chronic illnesses. He is the founder and co-director of the Mitochondrial and Metabolic Disease Center (MMDC), and Professor of Genetics in the departments of Medicine, Pediatrics, and Pathology, at the University of California, San Diego (UCSD) School of Medicine, where he directs a core laboratory for metabolomics. 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[1]—the oldest Mendelian form of mitochondrial disease—and the developer of the first DNA test to diagnose it[2]. His lab also discovered the first mitochondrial DNA (mtDNA) mutation to cause genetic forms of autism[3]. He identified the metabolic features of the cell danger response (CDR)[4], characterized the mitochondrial and metabolic features of the healing cycle[5], showed the connection between healing and aging[6], and how mitochondria respond to environmental pollution and ecosystem stress by activating the CDR and creating a link between environmental health and human health[7]. Naviaux’s lab developed some of the first methods to isolate metagenomic DNA from beach sand and ocean floor core sediments for use in the molecular reconstruction of modern and ancient marine ecosystems[8]. He also helped pioneer the use of biocavity laser spectroscopy to characterize the mitochondrial response to environmental stress9-11[9][10][11]. Dr. Naviaux 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)[12]. His lab has developed new methods in metabolomics[13][14] and environmental toxicology that have shown that many complex chronic disorders like ASD, chronic fatigue syndrome (ME/CFS)[15], and Gulf War Illness[16], have a metabolic signature that can be used in diagnosis and lead to fresh insights to treatment[17][18].

Early years

Naviaux is the oldest of four boys born to Barbara and Dr. James L. Naviaux, DVM. His father was a veterinarian specializing in horses, who also had a lifelong interest in wildlife medicine. In 1968, his father founded the National Wildlife Health Foundation, and in the aftermath of the Santa Barbara oil spills in 1969, played an instrumental role in developing new methods for the treatment of oil-covered birds. After his parents divorced in 1966, Naviaux and his brothers lived with their mother in Petaluma, California from 1966-1969. From 1969-1974, Naviaux was raised by his maternal grandparents in Fairfax, Marin County, California, just north of San Francisco. As a 13-year old boy, Naviaux vividly recalls watching Neil Armstrong take his first steps on the moon on a Heathkit television built by his grandfather. This experience, and his love of wildlife, the ocean, and the outdoors fostered by his family and scouting, set the tone for all his future academic interests.

Training

Naviaux began his undergraduate studies at the University of California, Davis in 1974. While at Davis, he was a member of the swimming and diving team. In 1976, he spent a semester as an undergraduate research intern at the National Institutes of Health (NIH) in Bethesda, MD, where he studied natural killer cell biology and cancer immunology with Howard Holden in the laboratory of Ron Herberman. From 1977-1978 Naviaux studied biochemistry and medical sociology at Georg August University in Göttingen, Germany as an education abroad student. Upon returning to Davis, he worked as an undergraduate research student in experimental hematology and immunology at the UC Davis Radiobiology Laboratory. Naviaux earned a Bachelor of Science in biological sciences at UC Davis in 1979. In 1981, he earned a master’s in zoology and microbiology from Indiana University in Bloomington, Indiana, where he worked in the lab of W. Dean Fraser. In 1982, he entered the School of Medicine at Indiana University in Indianapolis and became one of that university’s first medical scientist training program (MSTP) students. He received his MD in 1986, and his PhD in medical genetics and virology in 1989. He did his medical residency in the clinical investigator pathway of the American Board of Internal Medicine (ABIM) at UC Davis Medical Center, from 1986-1990. In 1990, Dr. Naviaux was named a National Medical Resident of the Year by the National Institute of Diabetes, Digestive, and Kidney Disease (NIDDK, NIH). He did his postdoctoral training in gene therapy and retrovirus biology with Inder Verma at the Salk Institute from 1990-1994, where he developed the popular pCL retroviral gene transfer vectors[19], and was a Fogarty International scholar in India in 1994. He did his medical subspecialty training in biochemical genetics and inborn errors of metabolism with William L. Nyhan and Richard H. Haas, from 1994-1997 at the University of California, San Diego (UCSD) School of Medicine. In 1996, Dr. Naviaux founded the Mitochondrial and Metabolic Disease Center (MMDC) at UCSD.

Research career

Dr. Naviaux joined the faculty of UCSD as an assistant professor in 1997. He has been a full professor of genetics in the departments of Medicine, Pediatrics, and Pathology at UCSD since 2009. After developing a sensitive biochemical assay for the mitochondrial DNA polymerase γ (POLG)[20], Naviaux found POLG to be deficient in a child with Alpers-Huttenlocher syndrome1. This was the first report of a defect in any DNA polymerase leading to a human genetic disease and brought to a close a 70-year old medical mystery about the cause of Alpers syndrome, which had first been described in 1931[21]. From 2003-2007, Naviaux studied the biophysical response of mitochondria to genetic and environmental stress in collaboration with Paul Gourley, the inventor of the biocavity laser, at Sandia National Labs in Albuquerque, NM[9][11]. From 2006-2009, Naviaux studied the role of mitochondria in regeneration and healing in the MRL mouse, working in collaboration with Ellen Heber-Katz at the Wistar Institute in Philadelphia[22]. In 2008, he was asked to study the connection between mitochondria and autism by the chairman of the board of the United Mitochondrial Disease Foundation (UMDF), W. Dan Wright. This early work led to the hyperpurinergia hypothesis[23] for the genesis and treatment of autism spectrum disorder (ASD), and to a Trailblazer Award from Autism Speaks in 2011. After successful testing in several mouse models of ASD[23][24][25], the antipurinergic drug suramin was tested as a treatment of autism in a small clinical trial of 10 children—the SAT-1 trial. The effects from a single dose of suramin were dramatic. Improvements were found in the ASD core symptoms of language, social behavior, and reductions in repetitive behaviors six weeks after a single dose in all children who received suramin and in none of the children who received placebo[12].

In the decade from 2008-2018, Naviaux coined the term “oxidative shielding” to reflect the observation that what had been thought of as oxidative “stress” for over 50 years, was actually an active process catalyzed by cell proteins to shield the cell and prevent the spread of environmental threats from microbial infection, toxicant exposure, and physical injury to neighboring cells[26]. Advances in mass spectrometry and metabolomics led to a reframing of the coordinated cellular response to injury and threat as the cell danger response, or CDR[27]. Once defined in metabolic terms, Naviaux showed that three different mitochondrial phenotypes—M1, M0, and M2—were developmentally programmed to support three specialized states of CDR1, 2, and 3, respectively, that each must be activated and extinguished in sequence to complete the healing cycle[5]. Later work showed that molecular hallmarks of cellular aging occur naturally and transiently after any injury. Naviaux showed that when healing is incomplete, dysfunctional cells accumulate over time and lead to age-related declines in physiologic reserve capacity and to biological aging. Dr. Naviaux first introduced the term “salugenesis” to describe the molecular, cellular, autonomic, neuroendocrine, and behavioral steps of the healing cycle, in a lecture in Sydney, Australia on March 23, 2019 for the MINDD Foundation, and at the National Institutes of Health on April 4, 2019 (https://www.youtube.com/watch?v=1emsA2CcRK4, time stamped 55:01 min).

In the media

              

References

  1. Naviaux, Robert K. (1999). "Mitochondrial DNA polymerase gamma deficiency and mtDNA depletion in a child with Alpers' syndrome". Annals of neurology (45): 54–58.
  2. Naviaux, Robert K.; Nguyen, K.V. (2004). "POLG Mutations Associated with Alpers' Syndrome and Mitochondrial DNA Depletion". Annals of neurology (55): 706–712.
  3. Graf, W.D. (2000). "Autism associated with the mitochondrial DNA G8363A transfer RNA(Lys) mutation". Journal of child neurology. 15: 357–361.
  4. Naviaux, R.K. (2014). "Metabolic features of the cell danger response". Mitochondrion (16): 7–17.
  5. 5.0 5.1 Naviaux, R.K. (2018). "Metabolic features and regulation of the healing cycle-A new model for chronic disease pathogenesis and treatment". Mitochondrion.
  6. Naviaux, R.K. (2019). "Incomplete healing as a cause of aging: the role of mitochondria and the cell danger response". Biology (MDPI).
  7. Naviaux, R.K. (2020). "Perspective: Cell danger response Biology-The new science that connects environmental health with mitochondria and the rising tide of chronic illness". Mitochondrion. 51: 40–45.
  8. Naviaux, R.K. (2005). "Sand DNA - a genetic library of life at the water's edge". Marine Ecology-Progress Series. 301: 9-22.
  9. 9.0 9.1 Gourley, P.L. (2007). "Reactive biomolecular divergence in genetically altered yeast cells and isolated mitochondria as measured by biocavity laser spectroscopy: rapid diagnostic method for studying cellular responses to stress and disease". J Biomed Opt. 12.
  10. Gourley, P.L. (2005). "Optical phenotyping of human mitochondria in a biocavity laser". IEEE J. Selected Topics Quantum Electronics. 11 (818–826).
  11. 11.0 11.1 Gourley, P.L. (2005). "Mitochondrial correlation microscopy and nanolaser spectroscopy - new tools for biophotonic detection of cancer in single cells". Technol Cancer Res Treat. 4 (585–592).
  12. 12.0 12.1 Naviaux, R.K. (2017). "Low-dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial". Ann Clin Transl Neurol. 4: 491-505.
  13. Li, K (2017). "A robust, single-injection method for targeted, broad-spectrum plasma metabolomics". Metabolomics : Official journal of the Metabolomic Society. 13: 122.
  14. Li, K (2020). "Improved Dried Blood Spot-Based Metabolomics: A Targeted, Broad-Spectrum, Single-Injection Method". Metabolites. 10.
  15. Naviaux, R.K. (2016). "Metabolic features of chronic fatigue syndrome". Proceedings of the National Academy of Sciences of the United States of America. 113 (E5472–5480).
  16. Naviaux, R.K. (2019). "Metabolic features of Gulf War illness". PloS One. 14: e0219531.
  17. Naviaux, R.K. (2018). "Metabolic features and regulation of the healing cycle-A new model for chronic disease pathogenesis and treatment". Mitochondrion.
  18. Naviaux, R.K. (2018). "Antipurinergic therapy for autism-An in-depth review". Mitochondrion. 43: 1–15.
  19. Naviaux, R.K. (1996). "The pCL vector system: rapid production of helper-free, high-titer, recombinant retroviruses". J Virol. 70: 5701–5705.
  20. Naviaux, R.K. (1999). "Sensitive assay for mitochondrial DNA polymerase gamma". Clinical chemistry. 45: 1725–1733.
  21. Naviaux, R.K. (2009). "Retained features of embryonic metabolism in the adult MRL mouse". Molecular genetics and metabolism. 96: 133–144.
  22. Naviaux, R.K. (2012). "Mitochondria and Autism. in The Neuroscience of Autism Spectrum Disorders". (eds. Buxbaum, J.D. & Hof, P.R.): 179–193.
  23. 23.0 23.1 Naviaux, R.K. (2013). "Antipurinergic Therapy Corrects the Autism-Like Features in the Poly(IC) Mouse Model". PloS One. 8: e57380.
  24. Naviaux, R.K. (2012). "Oxidative shielding or oxidative stress?". J Pharmacol Exp Ther. 342: 608–618.
  25. Naviaux, J.C. (2014). "Reversal of autism-like behaviors and metabolism in adult mice with single-dose antipurinergic therapy". Translational psychiatry. 4: e400.
  26. Naviaux, Robert K. (2019-05-11). "Incomplete Healing as a Cause of Aging: The Role of Mitochondria and the Cell Danger Response". Biology. 8 (2). doi:10.3390/biology8020027. ISSN 2079-7737. PMC 6627909. PMID 31083530.
  27. Naviaux, R.K (2014). "Metabolic features of the cell danger response". Mitochondrion. 16: 7–17.

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