About

Gary W. Falk, MD, MS, is an Emeritus Professor of Medicine (Gastroenterology) at the University of Pennsylvania's Perelman School of Medicine. He is a member of the Hospital of the University of Pennsylvania Abramson Comprehensive Cancer Center Cancer Control Research Program and holds the position of University Associate Staff at Children's Hospital of Philadelphia. Dr. Falk specializes in esophageal diseases, including Barrett's esophagus, eosinophilic esophagitis, GERD diagnosis and treatment, achalasia, motility abnormalities, extraesophageal GERD, dysphagia, and esophageal cancer. His research focuses on the chemoprevention, detection, diagnosis, and epidemiology of Barrett's esophagus and eosinophilic esophagitis, as well as advanced endoscopic imaging techniques. Dr. Falk's educational background includes a B.S. in Biology-Geology from the University of Rochester, an M.D. from the University of Rochester School of Medicine and Dentistry, and an M.S. in Clinical Research from Case Western Reserve University School of Medicine Clinical Scholars Program.

Research topics

• Medicine
• Internal medicine
• Pathology
• Biology
• Computer Science
• Gastroenterology
• Intensive care medicine
• Surgery
• Artificial Intelligence
• Cancer research
• Oncology
• Dermatology

Selected publications

• American Society for Gastrointestinal Endoscopy consensus recommendations on the endoscopic management of eosinophilic esophagitis―part 2: disease assessment, monitoring, and pediatric considerations

  Gastrointestinal Endoscopy · 2026-01-08 · 1 citations

  article
  PublisherDOI

• Interleukin-13 Promotes Accumulation of Esophageal Epithelial Mitochondria With Translational Implications for Eosinophilic Esophagitis

  Cellular and Molecular Gastroenterology and Hepatology · 2026-01-01

  articleOpen access

  BACKGROUND & AIMS: Metabolic and mitochondrial dysfunction have recently been implicated in eosinophilic esophagitis (EoE) pathogenesis. However, there is a need to define the influence of EoE-associated inflammatory cues upon mitochondrial biology, mechanisms mediating these effects, and the clinical significance of mitochondrial alterations in EoE. METHODS: Mitochondria were evaluated in human biopsies, MC903/ovalbumin-induced murine EoE, and human esophageal keratinocytes stimulated with EoE-relevant cytokines. Mitochondrial mediators were assessed via quantitative reverse transcription polymerase reaction and Western blotting. Metabolism, mitochondrial membrane potential, and apoptosis were measured. Mitochondrial DNA (mtDNA)-encoded genes, ND1 and ND6 were assessed by quantitative polymerase chain reaction in DNA from culture media and circulating nucleic acids from human serum samples. Effects of Janus kinase (JAK) inhibitor ruxolitinib or genetic inhibition of signal transducer and activator of transcription (STAT)3 or STAT6 on mitochondria were assessed in vitro. RESULTS: We identified evidence of increased mitochondria in esophageal mucosa of patients with EoE and mice with EoE-like inflammation. Interleukin (IL)-13 consistently induced mitochondrial accumulation in esophageal keratinocytes in vitro, and this response was associated with increased expression of mediators of mitochondrial biogenesis, fusion, and mitophagy. IL-13 suppressed mitochondrial respiration and adenosine triphosphate (ATP) production, without impacting membrane polarization or apoptosis. Patients with active EoE exhibited elevated serum mtDNA levels and upregulation of mediators of mtDNA-associated inflammatory signaling. Increased mitochondrial mass and accumulation of extracellular mtDNA in IL-13-treated esophageal keratinocytes were dependent on JAK/STAT signaling. CONCLUSIONS: We identify IL-13 as a mediator of increased mitochondrial mass in EoE through JAK/STAT signaling. We further demonstrate that IL-13 promotes accumulation of extracellular mtDNA and that circulating mtDNA is elevated in patients with EoE.

  PublisherDOI

• Development and Validation of a Large Language Model Case Identification Strategy for Eosinophilic Esophagitis

  Gastro Hep Advances · 2026-01-01

  articleOpen access

  Background and Aims: Epidemiologic research in eosinophilic esophagitis (EoE) is limited by the accuracy and efficiency of case identification algorithms. We aimed to evaluate rule-based natural language processing (RB-NLP) and large language model–based natural language processing (LLM-NLP) pipelines for identifying EoE diagnoses and features from unstructured text. Methods: We identified gastrointestinal pathology reports with any mention of “eosinophil” paired with gastroenterology clinic notes. Three hundred randomly selected patients were divided into training (n = 200, 56 with EoE) and testing (n = 100, 36 with EoE) sets. Manual chart review was the reference standard. RB-NLP used spaCy with medspaCy’s clinical components; LLM-NLP prompts were developed through iterative human-in-the-loop refinement. In the validation set, we compared International Classification of Diseases (ICD) codes, RB-NLP, and LLM-NLP against the reference standard using sensitivity (recall), positive predictive value (precision), and F1 score. Results: In the validation set, ICD codes alone had a sensitivity 0.86 (95% confidence interval [CI]: 0.75–0.97), a positive predictive value of 0.97 (95% CI: 0.91–1.0), and an F1 value of 0.91 (95% CI: 0.84–1.0). Combining ICD and LLM-assigned diagnosis yielded a 3-point improvement in F1 score (95% CI: −0.01 to 0.07; P = .2) compared to ICD alone. In a larger cohort (n = 580), the LLM + ICD approach identified the most EoE cases (n = 203) and captured 15% of cases missed by ICD codes. Clinical characteristics varied depending on the case identification strategy used. Conclusion: Combining LLM-NLP with a single ICD code reduced false negatives and modestly improved the F1 score compared to either method alone. This may represent a scalable approach to enhance EoE case identification in real-world data.

  PublisherDOI

• Non-epithelial Gene Expression Correlates with Symptom Severity in Adults with Eosinophilic Esophagitis

  UNC Libraries · 2025-05-19

  articleOpen access
  PublisherDOI

• Long-term Safety and Efficacy of Budesonide Oral Suspension for Eosinophilic Esophagitis: A 4-Year, Phase 3, Open-Label Study

  Clinical Gastroenterology and Hepatology · 2025-02-13 · 6 citations

  articleOpen access

  BACKGROUND & AIMS: We investigated the long-term safety and efficacy of budesonide oral suspension (BOS) in eosinophilic esophagitis (EoE). METHODS: This study (SHP621-303) was a 4-year, phase 3, open-label study in patients with EoE who completed up to 52 weeks of BOS therapy in 2 preceding phase 3 studies. On the basis of treatment assignments in previous studies, patients were assigned to BOS-BOS or placebo-BOS groups. All patients received BOS 2.0 mg twice daily; dose reductions to once daily and interruptions were permitted. The safety and tolerability of BOS were primarily investigated, with exploratory efficacy endpoints also examined. RESULTS: Overall, 131 patients were included. BOS was well-tolerated, with no unexpected safety signals observed. Treatment-emergent adverse events (TEAEs) occurred in 76.3% of patients; most were mild/moderate in severity and unrelated to study drug. The most frequently reported BOS-related TEAEs included abnormal adrenocorticotropic hormone stimulation test results (8.4%, 11/131; number of events [m] = 12) and adrenal insufficiency (2.3%, 3/131; m = 3). Esophageal candidiasis occurred in 3.1% of patients (4/131). The aforementioned TEAEs resolved in most patients. At month 48 of treatment, 50.0% and 58.3% of patients achieved/maintained a histologic response (≤6 and <15 eosinophils per high-power field, respectively). The initial reduction (-3.6) in total EoE Endoscopic Reference Score from baseline to the first visit was maintained until month 48. CONCLUSIONS: Long-term treatment with BOS was well-tolerated. Despite dosing changes/interruptions, approximately half of patients achieved/maintained a histologic response; initial improvements in endoscopic outcomes were maintained over 48 months. CLINICALTRIALS: gov number: NCT03245840.

  PublisherDOI

• S919 Large Language Models Combined With a Single Diagnostic Code Detect Eosinophilic Esophagitis in Electronic Health Records With High Accuracy

  The American Journal of Gastroenterology · 2025-10-01

  article

  Introduction: Large-scale epidemiologic research for eosinophilic esophagitis (EoE) is hampered by variable accuracy of International Classification of Diseases (ICD) codes and case identification algorithms. We aimed to develop and validate a natural language processing (NLP) pipeline using large language models (LLMs) to identify EoE features and diagnosis from unstructured text, comparing performance with ICD codes and ICD + LLM combination. Methods: We identified gastrointestinal pathology reports with any mention of “eosinophil” paired with preceding GI clinic notes. Three hundred randomly selected patients were divided into training (N = 200, 56 with EoE) and testing (N = 100, 36 with EoE) sets. Manual chart review was used to assign an EoE reference standard. LLM prompt development used a human-in-the-loop approach with iterative refinements. Training concluded once the LLM-assigned diagnosis exceeded the F1 score (harmonic mean of precision and recall) of ICD codes. Using the test set, we compared performance of ICD codes, LLM-derived diagnostic features, LLM-assigned diagnosis, and a combined LLM + ICD. Performance metrics included sensitivity (recall), PPV (precision), and F1 score. Nonparametric bootstrap resampling (1,000 replicates) was used to estimate 95% confidence intervals (CIs) with statistical significance based on whether they excluded zero. Results: In the training set, LLM-derived diagnostic features demonstrated the highest sensitivity (0.98; 95% CI 0.95, 1.00), while LLM-assigned diagnosis had the highest PPV (0.92; 95% CI 0.84-1.0) and specificity (0.97; 95% CI 0.95,1.00). Comparably high F1 scores were achieved with LLM-derived features (0.89; 95% CI 0.83, 0.95) and ICD + LLM diagnosis (0.88; 95% CI 0.81, 0.95). In the independent test set, ICD codes alone showed a sensitivity of 0.86 (95% CI 0.75, 0.97), PPV of 0.97 (95% CI 0.91, 1.0), and an F1 of 0.91 (95% CI 0.84, 1.0). Combining ICD and LLM-assigned diagnosis yielded a 3-point improvement in F1 score (95% CI -0.01, 0.07; P = 0.2) compared to ICD alone. This combination method significantly improved sensitivity (0.92 [0.83,1.00]; P = 0.008) and F1 score (0.94 [0.89,1.00]; P = 0.047) relative to LLM-assigned diagnosis. Conclusion: Combining the LLM-assigned diagnosis with a single diagnostic code reduced false negatives and modestly improved the F1 score compared to either method alone, suggesting a scalable approach for improving EoE case identification in real-world data.

  PublisherDOI

• Sa1236: EFFECT OF DISEASE SEVERITY ON HISTOLOGIC, DYSPHAGIA SYMPTOM AND ENDOSCOPIC OUTCOMES IN PATIENTS WITH EOSINOPHILIC ESOPHAGITIS: POST HOC ANALYSIS FROM A PHASE 3 TRIAL OF BUDESONIDE ORAL SUSPENSION

  Gastroenterology · 2025-05-01

  article
  PublisherDOI

• 791: DUPILUMAB IMPROVES HISTOLOGIC AND ENDOSCOPIC FEATURES OF EOSINOPHILIC GASTRITIS: RESULTS FROM THE MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 2 DEGAS TRIAL

  Gastroenterology · 2025-05-01

  article
  PublisherDOI

• Increased reflux secondary bile acids are associated with changes to the microbiome and transcriptome in Barrett’s esophagus

  Gut Microbes · 2025-08-22 · 8 citations

  articleOpen access

  showed the most associations with gene expression, including the oxidative phosphorylation pathway. We identified two distinct BE gene expression clusters independent of histology, bile acid, or microbiome composition. These findings suggest bile acids shape the BE microbiome and associate with gene expression changes potentially relevant to EAC development.

  PublisherOA PDFDOI

• Microbiota and metabolite-based prediction tool for colonic polyposis with and without a known genetic driver

  Gut Microbes · 2025-03-11 · 6 citations

  articleOpen access

  H NMR, revealing an increase in alanine in SPS subjects relative to non-polyposis subjects, and Partial Least Squares Discriminant Analysis (PLS-DA) analysis indicated that the proportion of leucine to tyrosine in fecal samples may be predictive of SPS. Use of these microbial and metabolomic signatures may allow for better diagnostric and risk-stratification tools for colonic polyposis patients and their families as well as promote development of microbiome-targeted approaches for polyp prevention.

  PublisherOA PDFDOI

Frequent coauthors

• Amitabh Chak

  249 shared

• William M. Grady

  243 shared

• Jacques Van Dam

  210 shared

• John M. Inadomi

  University of Utah

  209 shared

• Nicholas J. Shaheen

  207 shared

• Sanford D. Markowitz

  202 shared

• Prateek Sharma

  Vellore Institute of Technology University

  202 shared

• Sumeet K. Mittal

  196 shared

Labs

• Falk LabPI

Education

• MS, Clinical Scholars

  Case Western Reserve University

  2006

• MD, Medicine

  University of Rochester

  1980

• BS, Biology-Geology

  University of Rochester

  1976