About

Amanda B. Muir, MD, MTR, is an Associate Professor of Pediatrics specializing in Gastroenterology, Hepatology, and Nutrition at the Children's Hospital of Philadelphia. She serves as an Attending Physician at the same hospital and is the Co-Director of the Center for Pediatric Eosinophilic Disorders. Additionally, she is the Director of Pediatric GI Fellowship Research at the Children's Hospital of Philadelphia. Dr. Muir's educational background includes a Bachelor of Science in Biology from Amherst College (2001), an MD from the University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School (2007), and a Master’s in Translational Research from the University of Pennsylvania (2017). Her professional focus is on pediatric gastrointestinal disorders, with a particular emphasis on eosinophilic conditions.

Research topics

• Medicine
• Pathology
• Internal medicine
• Biology
• Gastroenterology
• Artificial Intelligence
• Computer Science
• Surgery
• Intensive care medicine

Selected publications

• Allergic and Eosinophilic Gastrointestinal Disease

  Elsevier eBooks · 2025-07-23

  book-chapter
  PublisherDOI

• Interleukin-13-mediated alterations in esophageal epithelial mitochondria contribute to tissue remodeling in eosinophilic esophagitis

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-02 · 2 citations

  preprintOpen access

  Background: The significance of mitochondria in EoE pathobiology remains elusive. Objective: To determine the impact of EoE inflammatory mediators upon mitochondrial biology in esophageal epithelium, the mechanisms mediating these effects, and their functional significance to EoE pathobiology. Methods: to Cre or siRNA against Transcription factor A, mitochondria (TFAM) was transfected into esophageal keratinocytes. Mitochondrial respiration, membrane potential, and superoxide levels were measured. Results: We find evidence of increased mitochondria in esophageal epithelium of patients with EoE and mice with EoE-like inflammation. In esophageal keratinocytes, IL-4 and IL-13 increase mitochondrial mass. IL-13 increases mitochondrial biogenesis in a JAK/STAT-dependent manner. In 3D organoids, IL-13 limits squamous cell differentiation (SCD), and this is blunted upon TFAM depletion. IL-13 decreases mitochondrial respiration and superoxide level, although mitochondria remain intact. IL-13-mediated suppression of superoxide was abrogated upon TFAM depletion in esophageal keratinocytes. Conclusions: We report that increased mitochondrial mass is a feature of EoE. Among EoE-relevant cytokines, IL-13 is the primary driver of increased mitochondrial mass in esophageal keratinocytes by promoting mitochondrial biogenesis in a JAK/STAT-dependent manner. IL-13-mediated accumulation of mitochondria impairs SCD in esophageal keratinocytes and also suppresses oxidative stress, a factor that is known to induce SCD. These findings identify a novel mechanism through which IL-13 promotes EoE-associated epithelial remodeling. Clinical Implication: These findings further lay a foundation for exploration of level of esophageal epithelial mitochondria as a predictive biomarker for response to dupilumab. Capsule summary: IL-13 promotes mitochondrial biogenesis in esophageal epithelium, contributing to impaired squamous cell differentiation.

  PublisherDOI

• Mitochondrial dysfunction drives basal cell hyperplasia in eosinophilic oesophagitis

  Gut · 2025-07-23 · 2 citations

  articleOpen access

  BACKGROUND: Eosinophilic oesophagitis (EoE) is a food allergen-induced inflammatory disorder characterised by interleukin (IL)-13-mediated oesophageal inflammation and epithelial basal cell hyperplasia (BCH). The role of mitochondria in EoE pathogenesis remains elusive. DESIGN: Prompted by single cell transcriptomics data, we interrogated the role of mitochondria in EoE pathobiology using patient biopsies, EoE-mouse models and oesophageal epithelial cells grown in monolayer and three-dimensional (3D) organoid cultures treated with EoE-relevant cytokines. 3D organoids and EoE-bearing mice were treated with omeprazole-a proton-pump inhibitor used as first-line EoE therapy. We performed CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) interference in mouse organoids to identify the key mitochondrial regulatory genes whose depletion may lead to BCH. We analysed mitochondrial membrane potential, mass and superoxide production by flow cytometry, cellular oxygen consumption by respirometry, mitochondrial structures and perturbation of cellular energy homeostasis by immunoblotting. RESULTS : Mitochondrial dysfunction appeared to be a hallmark of EoE-related BCH where mitochondrial structural damage was associated with impaired oxidative respiratory capacity, elevation of mitochondrial superoxide and decreased adenosine triphosphate (ATP) production, as corroborated by activation of the adenosine monophosphate (AMP) -activated protein kinase and suppression of mammalian target-of-rapamycin signalling. Depletion of PGC1A, the master regulator of mitochondria biogenesis, recapitulated EoE-related BCH, suggesting that mitochondrial dysfunction drives BCH. Further, omeprazole alleviated mitochondrial damage and dysfunction in EoE-related BCH modelled in mice and patient-derived organoids. CONCLUSION: Mitochondrial dysfunction is tightly linked to perturbation of redox homeostasis in EoE-related BCH, which is promoted by IL-13 and reversible with omeprazole treatment.

  PublisherOA PDFDOI

• Mitochondrial clone tracing within spatially intact human tissues

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-07-17 · 4 citations

  preprintOpen access

  Understanding tissue development and intra-tissue evolution requires the ability to trace clones in intact tissues coupled with high-plex molecular profiling preserving spatial context. However, current lineage tracing tools are incompatible with spatial omics. Here, we present SUMMIT (Spatially Unveiling Mitochondrial Mutations In Tissues), a spatially-resolved lineage tracing technology that integrates gene expression profiling with mitochondrial mutation-based clone identification. Unlike synthetic lineage recording methods, SUMMIT relies only on endogenous mutations and thus can be applied to human tissues. To address the compositional mixing of cell types within spatial spots, SUMMIT includes a rigorous statistical framework to confidently assign variants to specific cell subpopulations and achieves high power for spatially localized clones by pooling information across neighboring spots. We validated SUMMIT using a controlled model in which we mixed two cancer cell lines in a mouse tumor, then demonstrated it on multiple human tissues including Barrett's esophagus, gastric cardia, small bowel, and colorectal cancer. Across these samples, we distinguished between global mutations and mutations marking locally restricted clones. The coupled transcriptomic data allowed us to characterize the cell type composition within each clone and delineate their spatial configuration. This integrated approach provides a framework to understand spatially-defined clonal evolution in preserved human tissue.

  PublisherDOI

• ACG Clinical Guideline: Diagnosis and Management of Eosinophilic Esophagitis

  The American Journal of Gastroenterology · 2025-01-01 · 138 citations

  article

  Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease of the esophagus. It is diagnosed in the setting of symptoms of esophageal dysfunction and an eosinophilic predominant infiltrate in the esophagus. The condition is rapidly increasing in incidence and prevalence and is commonly encountered in gastroenterology and allergy practices, emergency departments, and primary care settings. Over the past decade, there have been paradigm shifts in disease diagnosis and management, increases in knowledge about EoE risk factors, natural history, and pathogenesis, and development of validated outcome metrics. This updated American College of Gastroenterology Clinical Guideline uses Grading of Recommendations, Assessment, Development, and Evaluation methodology to make recommendations across domains of diagnosis, treatment, monitoring and assessment of response, and pediatric-specific considerations. Proton pump inhibitors, topical steroids, empiric diet elimination, a biologic, and esophageal dilation are all recommended treatments; feeding therapy is used adjunctively in children with food aversion or feeding dysfunction. Monitoring with clinical, endoscopic, and histologic assessments is recommended to assess for treatment response and follow patients over time with maintenance therapy. When evaluating and following patients with EoE, consideration should be given to assessing and controlling both the inflammatory and fibrostenotic aspects of disease.

  PublisherDOI

• FOXM1 inhibition reduces IL-13-induced epithelial remodelling and inflammation in eosinophilic oesophagitis

  Gut · 2025-11-20 · 1 citations

  articleOpen accessSenior author

  BACKGROUND: Eosinophilic oesophagitis (EoE) is a chronic allergic disease characterised by oesophageal epithelial remodelling, barrier dysfunction and inflammation. The transcription factor forkhead box M1 (FOXM1) has been shown to be a key regulator of epithelial proliferation and inflammation in allergic asthma. OBJECTIVE: To investigate the role of FOXM1 in epithelial disruption in EoE and to evaluate the therapeutic potential of FOXM1 inhibition. DESIGN: FOXM1 expression was analysed in human oesophageal biopsies, patient-derived organoids and murine EoE models. Interleukin (IL)-13 stimulation was used to model EoE in vitro. Using FOXM1 inhibition via the small molecule Robert Costa Memorial drug-1 (RCM-1), small interfering RNA-mediated knockdown or FOXM1 overexpression, the roles of FOXM1 were assessed by histology, gene expression profiling, organoid formation rates, barrier integrity and proliferation assays. RNA sequencing and chromatin immunoprecipitation were performed to elucidate molecular mechanisms. RESULTS: FOXM1 was significantly upregulated in patients with active EoE and localised to the basal epithelium. IL-13 increased FOXM1 expression in vitro. FOXM1 inhibition restored differentiation markers, reduced basal cell hyperplasia and proliferation, and improved barrier function. In a murine model, RCM-1 reduced epithelial changes and eosinophil infiltration. Conversely, FOXM1 overexpression promoted basal cell hyperplasia and proliferation. Mechanistically, FOXM1 directly regulated cell cycle gene, cyclin B1, which was upregulated in EoE and downregulated on FOXM1 inhibition. RCM-1 reduced phosphorylated STAT6 under IL-13 stimulation. FOXM1 expression was driven in part by an IL-13-PI3K/AKT axis. CONCLUSION: FOXM1 plays a pivotal role in epithelial disruption in EoE by driving proliferation and impairing differentiation. Targeting FOXM1 restores epithelial homeostasis, mitigates inflammation and offers a novel therapeutic approach for EoE.

  PublisherOA PDFDOI

• Learning to Tolerate: Searching for the Cells Responsible for Food Antigen Tolerance

  Gastroenterology · 2025-09-29

  article1st authorCorresponding
  PublisherDOI

• Efficacy of Dupilumab on Facilitated Food Reintroduction in Eosinophilic Esophagitis

  Clinical Gastroenterology and Hepatology · 2025-10-01 · 1 citations

  articleOpen access

  BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is a chronic, type 2 inflammatory disease of the esophagus commonly triggered by food allergens. Eliminating dietary EoE trigger foods can effectively treat EoE in some cases, but maintaining adherence can be challenging and can reduce quality of life. We aimed to assess the efficacy of dupilumab on reintroducing these foods based on clinical outcomes in patients with EoE. METHODS: We conducted an open-label pilot study in which patients aged 6 to 25 years with EoE induced by milk, egg, soy, or wheat were treated with weight- and age-tiered dupilumab for 3 months, followed by standardized reintroduction of trigger foods at months 3, 6, and 9, while continuing on dupilumab treatment. Symptoms, histology, endoscopy, and esophageal diameter were compared prior to and following every phase of food reintroduction to month 12. All patients had previously failed trigger food reintroduction on their current EoE medication. RESULTS: Twenty-one patients were enrolled. All patients who completed the study were able to reintroduce at least one serving size of trigger foods by month 12, and 8 patients were able to add foods every 3 months. There was no worsening of any clinical outcome, including symptoms, histology, and esophageal diameter. There were no serious treatment-related adverse events. CONCLUSIONS: Patients with EoE treated with dupilumab were able to safely reintroduce EoE trigger foods into their diet without exacerbation of histologic, endoscopic, or symptomatic measures of EoE severity. Some patients were able to reintroduce food at an earlier timepoint than others. CLINICALTRIALS: gov, Number: NCT05247866.

  PublisherDOI

• Histologic Response Is Associated With Improved Esophageal Distensibility and Symptom Burden in Pediatric Eosinophilic Esophagitis

  Gastroenterology · 2025-08-18 · 3 citations

  articleOpen access
  PublisherOA PDFDOI

• Mouse models of eosinophilic esophagitis: molecular and translational insights

  American Journal of Physiology-Gastrointestinal and Liver Physiology · 2025-06-03 · 1 citations

  reviewOpen access

  Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory disease of the esophagus that exerts a significant clinical and financial burden in developed countries. Despite an emerging interest in this disease, the cellular and molecular mechanisms driving EoE pathogenesis remain elusive. Addressing this knowledge gap is critical to guide the development of novel approaches for diagnosis, monitoring, and therapy in patients with EoE. As EoE is an allergic inflammatory disorder that results in esophageal inflammation and tissue remodeling, in vivo studies are critical to develop a better understanding of this disease. Here, we provide a review of murine models of EoE, highlighting the mechanistic and translational insights into EoE pathogenesis and therapeutic approaches that studies using these models have uncovered. We further discuss the strengths and limitations of EoE mouse models, as well as opportunities for future in vivo approaches to study EoE. Overall, this article reviews the progress, challenges, unmet needs, and opportunities in murine modeling of EoE.

  PublisherDOI

Recent grants

• NIH Grant R21TR003039

  NIH · $422k · 2022

• NIH Grant K08DK10644401

  NIH · $151k · 2020

• NIH Grant K08DK106444

  NIH · $628k · 2020

• The Role of Lysyl Oxidase in Epithelial Differentiation in Eosinophilic Esophagitis

  NIH · $264k · 2019–2022

• NIH Grant F32DK100088

  NIH · $120k · 2015

Frequent coauthors

• Jonathan M. Spergel

  Children's Hospital of Philadelphia

  212 shared

• Glenn T. Furuta

  Children's Hospital Colorado

  85 shared

• Chris A. Liacouras

  University of Pennsylvania

  85 shared

• Sandeep K. Gupta

  Indiana University – Purdue University Indianapolis

  82 shared

• Alain Benitez

  79 shared

• Gary W. Falk

  78 shared

• Marc E. Rothenberg

  National Institute of Allergy and Infectious Diseases

  76 shared

• Antonella Cianferoni

  Children's Hospital of Philadelphia

  73 shared

Education

• B.S., Biology

  Amherst College

  2001

• M.D.

  University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School

  2007

• Other, Translational Research

  University of Pennsylvania

  2017