About

James G. Fox, PhD, is a Professor of Biological Engineering at MIT. His research focuses on infectious diseases of the gastrointestinal tract, particularly the pathogenesis of Campylobacter spp. and Helicobacter spp. infections in humans and animals. His laboratory has developed models such as the ferret for campylobacter and helicobacter-associated diseases, as well as the first rodent model to study helicobacter-associated gastric disease, including gastric cancer. Dr. Fox is recognized as an international authority on the epidemiology and pathogenesis of enterohepatic helicobacters, having identified, named, and described many diseases attributed to various Helicobacter species, including their links to hepatitis, liver tumors, inflammatory bowel disease, and colon cancer. His work has also elucidated the role of Helicobacter spp. in the development of cholesterol gallstones in mice, connecting these findings to human populations at high risk for gallbladder cancer. With over 35 years of experience, Dr. Fox has contributed significantly to understanding zoonotic diseases and biosafety issues related to in vivo models. He holds a Master of Science in Medical Microbiology from Stanford University and a Doctor in Veterinary Medicine from Colorado State University. He has served as the founding Director of the Division of Comparative Medicine, and has held leadership roles including past president of the American College of Laboratory Animal Medicine, the Massachusetts Society of Medical Research, and chairman of the AAALAC Council. In 2004, he was elected to the Institute of Medicine of the National Academy of Sciences.

Research topics

• Biology
• Immunology
• Medicine
• Internal medicine
• Cancer research
• Cell biology
• Neuroscience
• Genetics
• Psychology
• Microbiology
• Cognitive science

Selected publications

• In Memoriam: Pelayo Jesus Correa, MD (1927–2025)

  Gastroenterology · 2026-01-14

  articleOpen access
  PublisherOA PDFDOI

• Mo1422: LONGITUDINAL DEFINITION OF THE GASTRIC MICROBIOME FROM A HIGH GASTRIC CANCER-RISK COHORT FROM COLOMBIA, SOUTH AMERICA

  Gastroenterology · 2025-05-01

  articleSenior author
  PublisherDOI

• Temporal dynamics and metagenomics of phosphorothioate epigenomes in the human gut microbiome

  Microbiome · 2025-03-24 · 1 citations

  articleOpen access

  Abstract Background Epigenetic regulation of gene expression and host defense is well established in microbial communities, with dozens of DNA modifications comprising the epigenomes of prokaryotes and bacteriophage. Phosphorothioation (PT) of DNA, in which a chemically reactive sulfur atom replaces a non-bridging oxygen in the sugar-phosphate backbone, is catalyzed by dnd and ssp gene families widespread in bacteria and archaea. However, little is known about the role of PTs or other microbial epigenetic modifications in the human microbiome. Here we optimized and applied fecal DNA extraction, mass spectrometric, and metagenomics technologies to characterize the landscape and temporal dynamics of gut microbes possessing PT modifications. Results Exploiting the nuclease-resistance of PTs, mass spectrometric analysis of limit digests of PT-containing DNA reveals PT dinucleotides as part of genomic consensus sequences, with 16 possible dinucleotide combinations. Analysis of mouse fecal DNA revealed a highly uniform spectrum of 11 PT dinucleotides in all littermates, with PTs estimated to occur in 5–10% of gut microbes. Though at similar levels, PT dinucleotides in fecal DNA from 11 healthy humans possessed signature combinations and levels of individual PTs. Comparison with a widely distributed microbial epigenetic mark, m 6 dA, suggested temporal dynamics consistent with expectations for gut microbial communities based on Taylor’s Power Law. Application of PT-seq for site-specific metagenomic analysis of PT-containing bacteria in one fecal donor revealed the larger consensus sequences for the PT dinucleotides in Bacteroidota, Bacillota (formerly Firmicutes), Actinomycetota (formerly Actinobacteria), and Pseudomonadota (formerly Proteobacteria), which differed from unbiased metagenomics and suggested that the abundance of PT-containing bacteria did not simply mirror the spectrum of gut bacteria. PT-seq further revealed low abundance PT sites not detected as dinucleotides by mass spectrometry, attesting to the complementarity of the technologies. Conclusions The results of our studies provide a benchmark for understanding the behavior of an abundant and chemically reactive epigenetic mark in the human gut microbiome, with implications for inflammatory conditions of the gut.

  PublisherOA PDFDOI

• 0072 Single-cell transcriptome reveals keratinocyte subclusters that contribute to altered differentiation and inflammatory responses in atopic dermatitis

  Journal of Investigative Dermatology · 2025-07-21

  articleOpen access
  PublisherOA PDFDOI

• 280 TWEAK Links Psoriasis to Atopic-Like Inflammation through Paradoxical Reactions

  Journal of Investigative Dermatology · 2025-11-24

  articleOpen access
  PublisherOA PDFDOI

• Prophage dynamics in gastric and enterohepatic environments: unraveling ecological barriers and adaptive transitions

  ISME Communications · 2025-01-01 · 5 citations

  articleOpen access

  Abstract Phage predation plays a critical role in shaping bacterial genetic diversity, with prophages playing a comparable role. However, the prevalence and genetic variability of prophages within the Helicobacter genus remain inadequately studied. Helicobacter species are clinically significant and occupy distinct digestive system regions, with gastric species (e.g. Helicobacter pylori) residing in the gastric mucosa and enterohepatic species colonizing the liver and intestines of various vertebrates. Here, we address this knowledge gap by analyzing prophage presence and diversity across 343 non-pylori Helicobacter genomes, mapping their distribution, comparing genomic features between gastric and enterohepatic prophages, and exploring their evolutionary relationships with hosts. We identified and analyzed a catalog of 119 new complete and 78 incomplete prophages. Our analysis reveals significant differences between gastric and enterohepatic species. Gastric prophages exhibit high synteny, and cluster in a few groups, indicating a more conserved genetic structure. In contrast, enterohepatic prophages show greater diversity in gene order and content, reflecting their adaptation to varied host environments. Helicobacter cinaedi stands out, harboring a large number of prophages among the enterohepatic species, forming a distinct cohesive group. Phylogenetic analyses reveal a co-evolutionary relationship between several prophages and their bacterial hosts—though exceptions, such as the enterohepatic prophages from H. canis, H. equorum, H. jaachi, and the gastric prophage from H. himalayensis—suggesting more complex co-evolutionary dynamics like host jumps, recombination, and horizontal gene transfer. The insights gained from this study enhance our understanding of prophage dynamics in Helicobacter, emphasizing their role in bacterial adaptation, virulence, and host specificity.

  PublisherOA PDFDOI

• Molecular characterization of four <i>Helicobacter cetorum</i> strains from dolphins compared to human <i>Helicobacter pylori</i>

  Gut Microbes · 2025-09-25

  articleOpen access

  that arose after a host jump over 623,000 years ago, which is the coalescence time of the two species.

  PublisherDOI

• 0106 Single-cell and spatial transcriptomic analysis reveals regulatory Th17 cells and keratinocyte interactions driving inflammation in palmoplantar pustulosis

  Journal of Investigative Dermatology · 2025-07-21

  article
  PublisherDOI

• Surface expression of antitoxin on engineered bacteria neutralizes genotoxic colibactin in the gut

  Nature Microbiology · 2025-12-08 · 2 citations

  articleOpen access
  PublisherOA PDFDOI

• The Nucleoid Proteins Fis and IHF Positively Regulate the Gene Expression of Operons Responsible for Producing the Cytotoxins Tilimycin and Tilivalline in <i>Klebsiella oxytoca</i>

  International Journal of Microbiology · 2025-01-01 · 1 citations

  articleOpen access

  Introduction Klebsiella oxytoca causes antibiotic‐associated hemorrhagic colitis due to the production of the enterotoxins tilimycin and tilivalline. These toxins are synthesized by enzymes encoded in the aroX and NRPS operons, which are expressed divergently. This study investigated how the nucleoid‐associated proteins Fis and IHF regulate these operons and influence the production of enterotoxins. Methods We used reverse transcription quantitative PCR (RT‐qPCR) to assess the role of Fis and IHF in the transcription of the aroX and NRPS operons. Electrophoretic mobility shift assays (EMSAs) were used to examine the binding of Fis and IHF to the regulatory region. Additionally, Caco‐2 viability assays were performed using cells infected with WT, mutant, and complemented strains. Results RT‐qPCR demonstrated that deletions of fis or ihfA / ihfB significantly reduced operon expression. EMSA confirmed that Fis and IHF bind specifically to the regulatory region between the aroX and NRPS operons. Viability assays in Caco‐2 epithelial cells indicated increased host cell survival when exposed to the deletion mutants. Genetic complementation restored both transcription levels and cytotoxicity. Conclusions Fis and IHF are positive regulators of the aroX and NRPS operons, enhancing the production of tilimycin and tilivalline. These findings highlight the potential of targeting Fis and IHF for therapeutic intervention in antibiotic‐associated hemorrhagic colitis.

  PublisherDOI

Recent grants

• NIH Grant T32OD01097826

  NIH · $322k · 2018

• NIH Grant P01CA028842

  NIH · $27.7M · 2023

• NIH Grant T32OD010978

  NIH · $1.9M · 2018

• NIH Grant P01CA02884229

  NIH · $1.6M · 2016

• NIH Grant R01AI050952

  NIH · $1.3M · 2007

Frequent coauthors

• Timothy C. Wang

  Columbia University

  227 shared

• Sureshkumar Muthupalani

  160 shared

• Arlin B. Rogers

  Alnylam Pharmaceuticals (United States)

  148 shared

• Zhongming Ge

  134 shared

• Mark T. Whary

  Massachusetts Institute of Technology

  117 shared

• Nancy S. Taylor

  105 shared

• Zeli Shen

  Massachusetts Institute of Technology

  95 shared

• Shigeo Takaishi

  Kyoto University

  80 shared

Awards & honors

• Fellow of the Infectious Disease Society of America
• Elected to the Institute of Medicine of the National Academy…