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S Jill James, PhD
Professor of Pediatrics, University of Arkansas for Medical Sciences/College of Medicine/Department of Pediatrics
Director of the ACHRI Autism Metabolic Genomics Laboratory
Research Overview

For over two decades, biochemist Dr. S. Jill James has pioneered the study of the metabolic biomarkers of autism and genetic factors that may be mechanistically involved in the pathogenesis of autism at ACHRI.  As a result of her discovery of metabolic abnormalities in children with autism, she is widely respected in the autism scientific community and is sought out to present her findings at national and international conferences.  Specifically, she and her team have found in three independent case-control studies that plasma levels of metabolites important for detoxification and antioxidant capacity are significantly decreased in the children with autism relative to age-matched controls.  This decrease in antioxidant/detoxification capacity was associated with evidence of oxidative DNA damage and mitochondrial dysfunction in immune cells suggesting that children with autism may be more vulnerable to environmental factors that increase oxidative stress. More recently, she and her team have investigated brain tissues derived from individuals with autism and have found similar deficits in antioxidant capacity and evidence of brain inflammation and mitochondrial dysfunction in the autistic brain compared to unaffected control brain tissues. 

Dr. James’ work also encompasses cutting edge research into metabolic control of the “epigenetic” regulation of gene expression in immune cells and brain cells in autism that may provide mechanistic insights into immunologic and neurologic abnormalities in autism. These discoveries in the laboratory have provided the scientific rationale for intervention treatment trials targeted at improving metabolic balance as well as behavioral symptoms in the children. Her interest also extends to mothers of children with autism who exhibit similar metabolic abnormalities.  She collaborates with a National Institutes of Health network (EARLI study) and the University of California at Davis (MARBLES study) to investigate whether metabolic abnormalities during high risk pregnancies can predict an autism outcome. If this turns out to be true, interventions to normalize the metabolic abnormalities have potential to prevent occurrence/recurrence of autism and decrease the current high incidence of autism. 

In collaboration with doctors and psychologists from the UAMS Dennis Developmental Center, Dr. James is currently conducting a double-blind, placebo-controlled study to evaluate the efficacy of broad-spectrum nutritional supplementation in children with autism to normalize the metabolic imbalance, improve immune function and behavioral symptoms. Her passion for her work stems from her respect and compassion for the parents of children with autism and the potential for improvement in medical and behavioral symptoms with evidence-based nutritional interventions to normalize the metabolic imbalance in children with autism.

Key Publications

James SJ, Pogribna M, Pogribny IP, Melnyk S, Hine RJ, et al. Abnormal folate metabolism and mutation in the methylenetetrahydrofolate reductase gene may be maternal risk factors for Down Syndrome, Am. J. Clin. Nutr., 70: 495-501, 1999.

James SJ, Melnyk S, Pogribna M, Pogribny IP, and Caudill M. Evaluation of S-adenosylhomocysteine and DNA hypomethylation: potential epigenetic mechanisms for homocysteine-related pathology. Journal of Nutrition, 132: 2361S-2366S , 2002.

James S J . Maternal metabolic phenotype and Down syndrome: Beyond genetics. Invited editorial. Am. J. Med. Genet. 127A, 1-4, 2004.

James SJ. The molecular dynamics of folate metabolism and DNA methylation: implications for disease susceptibility and progression. Chapter 7 in Methylenetetrahydrofolate Reductase Polymorphisms and Disease, edited by Ueland PM and Rozen R. 2004

James SJ, Melnyk SB, Jernigan S, Janak L, Cutler P, Neubrander JM. Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with Autism. Amer. J. Clin. Nutr. 80:1611-17, 2004.

James SJ, Melnyk S, Fuchs G, Reid T, Jernigan S, Pavliv O, Hubanks A, Gaylor DW.  Efficacy of methylcobalamin and folinic acid treatment on glutathione redox status in children with autism.  Am J Clin Nutr. 2009 Jan;89(1):425-30.

James SJ, Rose S, Melnyk S, Jernigan S, Blossom S, Pavliv O, Gaylor DW. Cellular and mitochondrial glutathione redox imbalance in lymphoblastoid cells derived from children with autism. FASEB J. 2009 Mar 23.

James SJ, Melnyk S, Jernigan S, Pavliv O, Trusty T, Lehman S, Seidel L, Gaylor DW, Cleves MA. A functional polymorphism in the reduced folate carrier gene and DNA hypomethylation in mothers of children with autism. Am J Med Genet B Neuropsychiatr Genet. 2010 Sep;153B(6):1209-20.

Blossom SJ, Melnyk S, Cooney CA, Gilbert KM, James SJ. Postnatal exposure to trichloroethylene alters glutathione redox homeostasis, methylation potential, and neurotrophin expression in the mouse hippocampus. Neurotoxicology. 2012 Dec;33(6):1518-27.

Rose S, Melnyk S, Pavliv O, Bai S, Nick TG, Frye RE and James SJ. Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain. Translational Psychiatry, 2012 Jul 10;2:e134. doi: 10.1038/tp.2012.61 PMID: 22781167

Rose S, Melnyk S, Trusty TA, Pavliv O, Seidel, Li J, Nick T, and James SJ. Intracellular and Extracellular Redox Status and Free Radical Generation in Primary Immune Cells from Children with Autism, Autism Research and Treatment, 2012; 2012:986519. doi: 10.1155/2012/986519. PMID: 22928106

Melnyk S, Fuchs GJ, Schulz E, Lopez M, Kahler SG. Fussell JJ, Pavliv O, Rose S. Seidel L. Gaylor DW, James SJ. Metabolic Imbalance associated with methylation dysregulation and oxidative damage in children with autism. Journal of Autism and Developmental Disabilities 42:367-77, 2012. PMID: 21519954

James SJ, Shpyleva S, Melnyk S, Pavliv O, Pogribny IP. Complex epigenetic regulation of Engrailed-2 (EN-2) homeobox gene in the autism cerebellum. Transl Psychiatry. 2013 Feb 19;3:e232. doi: 10.1038/tp.2013.8. PMID: 23423141

*To find additional publications by this author, please visit Pubmed Central, a National Institutes of Health-operated site for electronic distribution of life sciences research reports.

Research Support

The National Institutes of Health: Metabolic Biomarkers of Autism: Genetic Predisposition and Nutritional Intervention

Environmental Protection Agency: Fallon Project

CDC: Mechanisms of Oxidative Stress in Children

Arkansas Children’s Hospital Foundation

Safeminds, Inc.


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