About

John F. Valentine, MD, is a Professor of Medicine at the University of Utah School of Medicine in the Division of Gastroenterology, Hepatology and Nutrition. He specializes in ulcerative colitis and Crohn's disease, with clinical interests and expertise in inflammatory diseases of the intestinal tract, including inflammatory bowel disease (IBD) and celiac disease. Dr. Valentine received his M.D. degree from the University of Texas Medical School at Houston in 1985, and completed his training in Internal Medicine at the Medical College of Virginia-Virginia Commonwealth University Medical Center, followed by Gastroenterology training at the University of Florida. While on faculty at the University of Florida, he rose to the position of Professor of Medicine, served as the Chief of the Gastroenterology Section at the Malcolm Randal Veterans Administration Medical Center, and founded the Southeastern Center for Inflammatory Bowel Disease. He remains active with the Crohn's and Colitis Foundation of America, having served as Co-Chair of the CCFA patient education committee and as a member of the editorial board for the journal Inflammatory Bowel Disease. Dr. Valentine is a Fellow in the American Gastroenterological Association and is the director of the University of Utah Inflammatory Bowel Disease Center. He has extensive experience in treating patients with inflammatory bowel disease and is involved in developing laboratory research and clinical trials in ulcerative colitis and Crohn's disease to expand understanding and treatment options for these conditions.

Research topics

• Medicine
• Genetics
• Gastroenterology
• Internal medicine
• Biology
• Immunology
• Machine Learning
• Computational biology
• Computer Science
• Pathology
• Microbiology
• Intensive care medicine

Selected publications

• Restricting Metabolic Plasticity Enhances Stress Adaptation Through the Modulation of Pdh and Hif1a in Trap1-Depleted Colon Cancer

  SSRN Electronic Journal · 2025-01-01

  preprintOpen access
  PublisherDOI

• The Utility of the Immunoglobulin A Flag Used in Celiac Disease Serology Testing on a Particle-Based Multianalyte Technology Platform

  Clinical Chemistry · 2025-04-25

  article
  PublisherDOI

• TNF Promoter Hypomethylation Is Associated With Mucosal Inflammation in IBD and Anti-TNF Response

  Gastro Hep Advances · 2024-01-01 · 2 citations

  articleOpen access

  Background and Aims: Inflammatory bowel diseases (IBDs) are chronic inflammatory conditions influenced heavily by environmental factors. DNA methylation is a form of epigenetic regulation linking environmental stimuli to gene expression changes and inflammation. Here, we investigated how DNA methylation of the tumor necrosis factor (TNF) promoter differs between inflamed and uninflamed mucosa of IBD patients, including anti-TNF responders and nonresponders. Methods: We obtained mucosal biopsies from 200 participants (133 IBDs and 67 controls) and analyzed TNF promoter methylation using bisulfite sequencing, comparing inflamed with uninflamed segments, in addition to paired inflamed/uninflamed samples from individual patients. We conducted similar analyses on purified intestinal epithelial cells from bowel resections. We also compared TNF methylation levels of inflamed and uninflamed mucosa from a separate cohort of 15 anti-TNF responders and 17 nonresponders. Finally, we sequenced DNA methyltransferase genes to identify rare variants in IBD patients and functionally tested them using rescue experiments in a zebrafish genetic model of DNA methylation deficiency. Results: TNF promoter methylation levels were decreased in inflamed mucosa of IBD patients and correlated with disease severity. Isolated intestinal epithelial cells from inflamed tissue showed proportional decreases in TNF methylation. Anti-TNF nonresponders showed lower levels of TNF methylation than responders in uninflamed mucosa. Our sequencing analysis revealed 2 missense variants in DNA methyltransferase 1, 1 of which had reduced function in vivo. Conclusion: Our study reveals an association of TNF promoter hypomethylation with mucosal inflammation, suggesting that IBD patients may be particularly sensitive to inflammatory environmental insults affecting DNA methylation. Together, our analyses indicate that TNF promoter methylation analysis may aid in the characterization of IBD status and evaluation of anti-TNF therapy response.

  PublisherOA PDFDOI

• <i>TNF</i> promoter hypomethylation is associated with mucosal inflammation in IBD and anti-TNF response

  medRxiv · 2024-02-06

  preprintOpen access

  Abstract Background and aims Inflammatory Bowel Diseases (IBD) are chronic inflammatory conditions influenced heavily by environmental factors. DNA methylation is a form of epigenetic regulation linking environmental stimuli to gene expression changes and inflammation. Here, we investigated how DNA methylation of the TNF promoter differs between inflamed and uninflamed mucosa of IBD patients, including anti-TNF responders and non-responders. Methods We obtained mucosal biopsies from 200 participants (133 IBD and 67 controls) and analyzed TNF promoter methylation using bisulfite sequencing, comparing inflamed with uninflamed segments, in addition to paired inflamed/uninflamed samples from individual patients. We conducted similar analyses on purified intestinal epithelial cells from bowel resections. We also compared TNF methylation levels of inflamed and uninflamed mucosa from a separate cohort of 15 anti-TNF responders and 17 non-responders. Finally, we sequenced DNA methyltransferase genes to identify rare variants in IBD patients and functionally tested them using rescue experiments in a zebrafish genetic model of DNA methylation deficiency. Results TNF promoter methylation levels were decreased in inflamed mucosa of IBD patients and correlated with disease severity. Isolated IECs from inflamed tissue showed proportional decreases in TNF methylation. Anti-TNF non-responders showed lower levels of TNF methylation than responders in uninflamed mucosa. Our sequencing analysis revealed two missense variants in DNMT1 , one of which had reduced function in vivo . Conclusions Our study reveals an association of TNF promoter hypomethylation with mucosal inflammation, suggesting that IBD patients may be particularly sensitive to inflammatory environmental insults affecting DNA methylation. Together, our analyses indicate that TNF promoter methylation analysis may aid in the characterization of IBD status and evaluation of anti-TNF therapy response.

  PublisherOA PDFDOI

• A Randomized Phase II Study of Efmarodocokin Alfa, an interleukin-22 Agonist, Versus Vedolizumab in Patients With Ulcerative Colitis

  Clinical Gastroenterology and Hepatology · 2024-12-16 · 10 citations

  article
  PublisherDOI

• Increased Activity of MAPKAPK2 within Mesenchymal Cells as a Target for Inflammation-Associated Fibrosis in Crohn’s Disease

  Journal of Crohn s and Colitis · 2024-01-15 · 3 citations

  article

  BACKGROUND: Mesenchymal stromal cells are suggested to play a critical role in Crohn's disease [CD]-associated fibrosis. MAPKAPK2 [MK2] has emerged as a potential therapeutic target to reduce inflammation in CD. However, the cell-specific pattern of phospho-MK2 activation and its role in CD-associated fibrosis are unknown. The objectives of this study were to evaluate cell-specific changes in MK2 activity between predominantly inflammatory CD vs CD with fibrotic complications and define the role of stromal cell-specific MK2 activation in CD-associated fibrosis. METHODS: CD tissue, CD tissue-derived mesenchymal stromal cells known as myo-/fibroblasts [CD-MFs], and fibroblast-specific MK2 conditional knockout [KO] mice were used. RESULTS: In the inflamed area of predominantly inflammatory CD, high MK2 activity was equally distributed between mesenchymal and haematopoietic cells. By contrast, in CD with fibrotic complications, high MK2 activity was mostly associated with mesenchymal stromal cells. Using ex vivo CD tissue explants and an IL-10KO murine colitis model, we demonstrated that pro-fibrotic responses are significantly reduced by treatment with the MK2 inhibitor PF-3644022. Inhibition of MK2 activity in primary cultures of CD-MFs significantly reduced basal and TGF-β1-induced profibrotic responses. Using fibroblast-specific MK2 knockout mice in chronic dextran saline sulphate colitis, we demonstrated that fibroblast intrinsic MK2 signalling is among the key processes involved in the chronic inflammation-induced profibrotic responses. CONCLUSIONS: Our data suggest that activation of MK2 within fibroblasts contributes to the chronic inflammation-induced fibrosis in CD and that targeting MK2 has potential for the development of novel therapeutic approaches for fibrosis in CD.

  PublisherDOI

• Surgery for Crohn’s Disease Is Associated With a Dysbiotic Microbiome and Metabolome: Results From Two Prospective Cohorts

  Cellular and Molecular Gastroenterology and Hepatology · 2024-01-01 · 14 citations

  articleOpen access

  BACKGROUND & AIMS: Crohn's disease is associated with alterations in the gut microbiome and metabolome described as dysbiosis. We characterized the microbial and metabolic consequences of ileal resection, the most common Crohn's disease surgery. METHODS: H nuclear magnetic resonance spectroscopy. Fecal bile acids and plasma 7α-hydroxy-4-cholesten-3-one (C4) was measured with mass spectrometry. RESULTS: Intestinal resection was associated with reduced alpha diversity and altered beta diversity with increased Proteobacteria and reduced Bacteroidetes and Firmicutes. Surgery was associated with higher representation of genes in the KEGG pathway for ABC transporters and reduction in genes related to bacterial metabolism. Surgery was associated with reduced concentration of the But gene but this did not translate to reduced fecal butyrate concentration. Surgery was associated with decreased abundance of bai operon genes, with increased plasma C4 concentration, increased primary bile acids and reduced secondary bile acids, including isoLCA. Additionally, Egerthella lenta, Adlercreutzia equalofaciens, and Gordonibacter pamelaeae were lower in abundance among patients with prior surgery in both cohorts. CONCLUSIONS: In 2 different populations, prior surgery in Crohn's disease is associated with altered fecal microbiome. Patients who had undergone ileal resection had reduction in the potentially beneficial bacteria E lenta and related actinobacteria and secondary bile acids, including isoLCA, suggesting that these could be biomarkers of patients at higher risk for disease progression.

  PublisherDOI

• S1201 Intravenous Immunoglobulin for Treatment of Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

  The American Journal of Gastroenterology · 2023-10-01

  reviewSenior author

  Introduction: The use of intravenous immunoglobulin (IVIg) for the treatment of inflammatory bowel disease (IBD) has been explored in patients with active infections or lack of response to therapeutic agents. However, efficacy data of IVIg in this latter setting are scarce. We conducted a meta-analysis to evaluate the efficacy of IVIg in IBD patients in whom immunosuppressive drugs either failed or were contraindicated. Methods: A systematic literature search was performed using the keywords “inflammatory bowel disease,” “Crohn’s disease,” “ulcerative colitis,” and “intravenous immunoglobulin” through November 2022. Studies with IBD patients treated with IVIg were included in the analysis. Case reports were excluded. The efficacy of the IVIg therapy was assessed by pooled estimate of clinical remission rate, clinical response rate, and means difference of the Crohn's Disease Activity Index (CDAI). Results: Nine studies met eligibility criteria, including 197 patients: 135 Crohn’s disease (68%), 43 ulcerative colitis (22%), and 19 unclassified (10%). Patients received either single or multiple doses of IVIg at 0.4 g/kg or 10 g/day as monotherapy or in addition to their current treatment regimen. The pooled estimate of clinical response rate (n: 5 studies) following at least one dose of IVIg was 65% (95% CI: 57%-72%) (Figure 1A). Among 3 studies, the pooled estimate of clinical remission rate was 49% (95% CI: 32%-68%) (Figure 1B). The CDAI score showed a significant decline with a pooled estimate of mean CDAI difference of 102 (95% CI: 26-178) (Figure 1C). Minor adverse events (e.g., headache, low-grade fever, myalgia) were reported in 17% of patients. No serious adverse events were observed. Conclusion: This study shows that IVIg is a safe and effective treatment for IBD patients with a lack of response or contraindication to immunosuppressive therapy. Randomized trials are needed to assess long-term clinical and endoscopic response to IVIg in this population.Figure 1.: Forest plots evaluating pooled estimates of A) clinical response, B) remission, and C) difference in mean Crohn's Disease Activity Index (CDAI) when intravenous immunoglobulin (IVIg) is used to treat inflammatory bowel disease (IBD).

  PublisherDOI

• Early Remission With Induction Therapy Predicts Long-Term Remission in Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis

  The American Journal of Gastroenterology · 2023-05-19 · 4 citations

  review

  Mohan, Babu P. MD, MS; Fatima, Noor MBBS; Khan, Shahab R. MBBS; Kassab, Lena MD, MBA; Chandan, Saurabh MD; Asokkumar, Ravishankar MBBS, FRCP; Valentine, John F. MD; Navaneethan, Udayakumar MD; Kochhar, Gursimran S. MD; Ma, Christopher MD, MPH; Jairath, Vipul MBChB, PhD, MRCP; Singh, Siddharth MD, MS Author Information

  PublisherDOI

• Incidence of retained biopsy specimens after esophagogastroduodenoscopy and colonoscopy

  Endoscopy International Open · 2023-05-23 · 1 citations

  articleOpen access

  Abstract Background and study aims In gastrointestinal endoscopy, biopsies must transit through the accessory channel and cap, presenting an opportunity for loss of tissue. We sought to determine the incidence of specimen retention in the accessory channel or cap and identify procedure characteristics associated with specimen retention. Patients and methods After completion of standard endoscopic procedures in which biopsies were obtained, the biopsy cap and accessory channel were inspected, brushed, and irrigated for any retained biopsy specimens according to a standard protocol. For controls, the same protocol was applied to procedures in which biopsies were not obtained. Specimen bottles from the recovery protocol were sent for pathological examination regardless of whether any visible tissue was present. Results A total of 216 outpatient procedures were included: 55 esophagogastroduodenoscopies (EGDs) and 50 colonoscopies in which biopsies were obtained and 56 EGDs and 55 colonoscopies in the control group. Retained specimens were found in either the cap or channel in 50 of 105 (48%). In 20 of 105 (19%), retained specimens were found just in the cap, in six of 105 (5.7%), retained specimens were found just in the channel, while in 24 of 105 (23%), retained specimens were found in both the cap and channel. Retained specimens were more likely to be found in EGDs compared to colonoscopies (58% vs. 36%, P = 0.031). No retained specimens were found in the control group. Conclusions Retained specimens are startingly common in standard gastrointestinal endoscopic procedures and could potentially change diagnoses and management. Quality improvement measures should be instituted to monitor prevalence of retained biopsies and methods to prevent them should be developed.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01DK054919

  NIH · $723k · 2003

• NIH Grant T32DK060443

  NIH · $1.6M · 2011

Frequent coauthors

• Beth S. Slomine

  Kennedy Krieger Institute

  360 shared

• Richard Holubkov

  University of Utah

  288 shared

• James R. Christensen

  Johns Hopkins University

  288 shared

• Frank W. Moler

  University of Michigan–Ann Arbor

  288 shared

• J. Michael Dean

  University of Utah

  216 shared

• Faye S. Silverstein

  University of Michigan–Ann Arbor

  216 shared

• Kathryn A. Peterson

  University of Utah

  202 shared

• Kajsa E. Affolter

  University of Utah

  202 shared

Education

• M.D.

  University of Texas Medical School at Houston

  1985

• Other, Internal Medicine

  Medical College of Virginia-Virginia Commonwealth University Medical Center

• Other, Gastroenterology

  University of Florida

Awards & honors

• Fellow in the American Gastroenterological Association