About

Kathryn (Kate) Hamilton, PhD, is an Associate Professor of Pediatrics specializing in Gastroenterology, Hepatology, and Nutrition at the University of Pennsylvania School of Medicine. She is a faculty member within the Institute for Translational Medicine and Therapeutics (ITMAT) and the Institute for Regenerative Medicine (IRM). Dr. Hamilton co-directs the Gastrointestinal Epithelial Modeling Program at Children's Hospital of Philadelphia, serving as a hub for patient-focused gastrointestinal organoid research and fostering collaborations across the Penn-CHOP campus and nationally. Her research expertise centers on understanding mechanisms regulating the gut epithelium in health and disease. Her laboratory employs in vivo models and patient-derived organoids to investigate the molecular basis of intestinal regeneration, particularly in inflammatory bowel disease (IBD). Her work spans themes such as post-transcriptional regulation by RNA binding proteins, behavior of epithelial stem cells in chronic gastrointestinal diseases, and fundamental intestinal epithelial biology through organoid studies from patients with rare monogenic IBD. Dr. Hamilton's research incorporates molecular and cellular biology, mammalian physiology, and human organoid biology, utilizing techniques like tissue culture, live cell microscopy, molecular biology, histological analyses, flow cytometry, in vivo models, single-cell transcriptomics, and epitranscriptomics. She is also a co-founder and co-director of the CHOP Gastrointestinal Epithelium Modeling (GEM) Program, which supports patient-focused research and collaboration in gastrointestinal organoid studies. Her contributions include evaluating pathways involved in epithelial cell death, stem cell behavior, and epigenetic alterations in gastrointestinal diseases, with a focus on translating these findings into therapeutic strategies.

Research topics

• Cell biology
• Genetics
• Biology
• Medicine
• Chemistry
• Internal medicine
• Biochemistry
• Gastroenterology

Selected publications

• Guiding Principles: Reporting Elements for Gastrointestinal Organoid Research

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

  articleOpen accessSenior author

  Gastrointestinal (GI) organoids are now widely used for disease modeling, drug discovery, regenerative-, and precision medicine. As publications using GI organoids have increased exponentially, methodological reporting across GI organoid studies remains inconsistent, making results difficult to interpret, compare, and reproduce. To address this, we present community-informed guidance for reporting key experimental details in GI organoid research. Our recommendations were developed by integrating established biomedical reporting frameworks, organoid-focused resources from international organizations, and structured input from the GI organoid community through an expert panel survey. These inputs informed a core set of reporting items, including stem cell source and donor context, media and supplement composition, extracellular matrix type, culture configuration, and other parameters essential for replication. We provide an "Organoid Reporting Toolkit" containing practical checklists and templates intended to help authors, reviewers, editors, and journals. Together, these resources aim to improve transparency and reproducibility, facilitate cross-study comparison, and streamline communication in the GI organoid field while preserving flexibility for methodological innovation.

  PublisherDOI

• A Shared Framework for Gastrointestinal Organoid Research: It’s Time

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

  articleOpen access1st authorCorresponding
  PublisherDOI

• Guiding Principles: A New Article Type to Promote Rigor, Reproducibility, and Transparency

  Cellular and Molecular Gastroenterology and Hepatology · 2025-09-03

  editorialOpen accessSenior author

  Technologies and approaches in gastrointestinal research are emerging and evolving rapidly, yet clear consensus on best practices for these methods often lags. Such ambiguity can compromise rigor, reproducibility, and transparency, risking meaningful advancements. Therefore, CMGH is excited to introduce Guiding Principles, a new article format to support scientific consistency and veracity by tackling research ‘gray areas.’ Guiding Principles articles will delineate a framework that the gastrointestinal research community can apply to complex experimental paradigms, such as key experimental and analytical considerations and reporting standards.

  PublisherOA PDFDOI

• An Epigenetic Basis for Sustained Inflammatory Epithelial Progenitor Cell States in Crohn’s Disease

  Cellular and Molecular Gastroenterology and Hepatology · 2025-10-21 · 1 citations

  articleOpen accessSenior author

  BACKGROUND & AIMS: Defining consequential differences in intestinal epithelial stem cells in healthy humans vs those with inflammatory bowel disease (Crohn's disease and ulcerative colitis) is essential for the development of much needed therapies to restore the epithelial barrier and maintain its fidelity. METHODS: We used single-cell transcriptomic and epigenomic approaches in matched patient tissues and organoids to investigate epithelial gene expression and function in children with no pathological diagnosis in the lower gastrointestinal tract and healthy adults compared with those with Crohn's disease. RESULTS: We identify an inflammatory secretory progenitor (ISP) cell state present almost exclusively in patients with Crohn's disease compared with healthy subjects. ISPs exhibit gene expression profiles consistent with normal secretory progenitor cells but concomitantly express a suite of distinguishing pro-inflammatory genes. Mechanistically, ISPs exhibit open chromatin at ISP gene loci. Although ISP-specific genes are not expressed in intestinal stem cells, their chromatin is accessible in Crohn's disease stem cells, suggesting that ISP genes are epigenetically poised in stem cells and subsequently transcriptionally activated in ISPs in the presence of inflammatory stimuli. Consistently, Crohn's disease colonoids exhibit sustained ISP gene expression that can be elicited further with pro-inflammatory cytokines or via co-culture with pro-inflammatory macrophages. CONCLUSIONS: We have defined differences in the epithelial stem and progenitor compartment of patients with Crohn's disease that suggest aberrant stem cell differentiation and inflammatory gene expression arise and persist during disease.

  PublisherDOI

• 552: EPITHELIAL SKIV2L DELETION INCREASES ER STRESS, PROMOTING ABERRANT SECRETORY CELL DIFFERENTIATION IN THE SMALL INTESTINE

  Gastroenterology · 2025-05-01

  articleSenior author
  PublisherDOI

• LCN2 contributions to an altered secretory environment in the intestinal epithelium in Crohn’s disease

  Physiology · 2025-05-01

  articleSenior author

  Background: The intestinal epithelium is a single but heterogeneous layer of cells that acts as a barrier between the luminal contents of the gastrointestinal tract and underlying mucosa. In patients with inflammatory bowel disease (IBD), dysregulated immune response and impaired mucosal healing lead to chronic inflammation. Our lab has identified a unique cell state, termed inflammatory secretory progenitor (ISP) cell state, in the intestinal epithelium of pediatric patients with Crohn’s disease. ISP gene expression is found in OLFM4-/REG1A+ secretory progenitors that maintain an inflammatory profile with the expression of immune-related and antimicrobial peptides, and antigen presentation proteins. We posit that the presence of cells in an ISP state may modulate epithelial response to injury and sustained inflammation, such as impaired repair that poises the epithelium for exacerbated disease pathogenesis or oncogenesis. Consistent with previous findings that show it is upregulated in Crohn’s, one of the ISP markers is lipocalin-2 (LCN2). First identified for its role in innate immunity, LCN2 is a secreted molecule expressed by multiple cell types. LCN2 can facilitate cellular uptake of different small weight molecules, including iron-binding compounds. Epithelial cell expression of LCN2 could therefore modify local iron stores during intestinal inflammation and repair. Mice with whole body deletion of Lcn2 are more sensitive to bacterial infection, but also appear to be less susceptible to acute colitis. No established role for epithelial expression of LCN2 in patients with IBD exists. The functional consequence of ISPs has yet to be determined, and thus the contribution of individual markers like LCN2 to disease development is not clear. We hypothesize: that ISPs give rise to an inflamed secretory environment in part via the upregulation of LCN2 which contributes to epithelial barrier damage. Methods: Stem cell derived 3D organoids allow us to examine epithelial-intrinsic defects that may contribute to disease. Given LCN2’s role in iron modulation, we generated Lcn2 knockdown colonoids—organoids derived from colonic epithelium— to probe sensitivity to iron-mediated cell death (ferroptosis) and inflammatory cytokines using organoid morphology, western blot, and immunostaining. We also evaluated single cell RNA-sequencing data for LCN2 expression in ISP and other cell types and confirmed findings using immunostaining in control and Crohn’s colonoids with or without cytokine treatment. Results & conclusions: Preliminary data show that Lcn2 KD murine colonoids show no morphological differences to control colonoids but exhibited reduced expression of ferroptosis marker TFRC at homeostasis and under cytokine stimulation via western blot. Cytokine-stimulated control colonoids exhibited increased membrane localization of TFRC compared to Lcn2 KD colonoids via immunostaining. Given goblet cells are the primary secretory cell type in the colon, our human data at the single cell and protein level (immunostaining) also support that goblet cell expression of LCN2 is altered in Crohn’s patients and under cytokine stimulation in Crohn’s disease colonoids. Taken together, our data suggest that LCN2 expression in ISPs may promote enhanced susceptibility of secretory progenitors and goblet cells to ferroptosis. Thus, the presence of ISPs may promote an aberrant secretory phenotype in the intestinal epithelium by altering the antimicrobial peptide content and susceptibility to cell death. Ongoing and future studies will evaluate whether this altered secretory phenotype contributes directly to alterations in mucus secretion and composition, and immune-epithelial crosstalk. University of Pennsylvania School of Veterinary Medicine; Institute for Infectious & Zoonotic Disease Martin and Pamela Winter Infectious Disease Pre-Doctoral Fellowship This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

  PublisherDOI

• Gastric epithelium from <i>BRCA1</i> and <i>BRCA2</i> carriers harbors increased double-stranded DNA damage and augmented growth

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-03

  preprintOpen access

  Abstract An accumulating body of evidence suggests carriers of a pathogenic germline variant (PGV) in BRCA1 or BRCA2 have increased gastric cancer (GC) risk. BRCA1 and BRCA2 are tumor suppressor genes involved in promoting homologous recombination to repair double-stranded DNA breaks. The aim of this investigation was to identify differences within the gastric epithelium and in patient-derived gastric organoids (PDGOs) between BRCA1 and BRCA2 carriers and non-carriers to determine if evidence of early gastric carcinogenesis exists amongst these carriers. First, using gastric epithelial biopsies, BRCA2 carriers were found to harbor higher expression of the proliferative marker Ki-67 within the antral gastric epithelium and strikingly, biopsies from both BRCA1 and BRCA2 carriers displayed a marked increase in double-stranded DNA damage. These results were further explored using PDGOs, where a growth advantage was observed for both BRCA1 and BRCA2 PDGOs compared to non-carrier PDGOs. Furthermore, both BRCA1 and BRCA2 PDGOs displayed a more pronounced enhancement of Ki-67 expression as well as increased double stranded DNA damage compared to non-carrier PDGOs. Importantly, none of the PDGOs showed signs of BRCA1 or BRCA2 loss of heterozygosity, potentially indicating a haploinsufficient phenotype. Taken together, these novel findings suggest that haploinsufficiency in BRCA1 and BRCA2 carriers may lead to DNA damage in the gastric epithelium, which may serve as an early event contributing to GC development.

  PublisherOA PDFDOI

• Mo1241 GASTRIC EPITHELIUM AND PATIENT-DERIVED GASTRIC ORGANOIDS FROM BRCA1/2 CARRIERS HARBOR INCREASED PROLIFERATION AND DNA DAMAGE

  Gastroenterology · 2024-05-01

  article
  PublisherDOI

• Lysyl Oxidase Regulates Epithelial Differentiation and Barrier Integrity in Eosinophilic Esophagitis

  Cellular and Molecular Gastroenterology and Hepatology · 2024-01-01 · 8 citations

  articleOpen access

  BACKGROUND & AIMS: Epithelial disruption in eosinophilic esophagitis (EoE) encompasses both impaired differentiation and diminished barrier integrity. We have shown that lysyl oxidase (LOX), a collagen cross-linking enzyme, is up-regulated in the esophageal epithelium in EoE. However, the functional roles of LOX in the esophageal epithelium remains unknown. METHODS: We investigated roles for LOX in the human esophageal epithelium using 3-dimensional organoid and air-liquid interface cultures stimulated with interleukin (IL)13 to recapitulate the EoE inflammatory milieu, followed by single-cell RNA sequencing, quantitative reverse-transcription polymerase chain reaction, Western blot, histology, and functional analyses of barrier integrity. RESULTS: Single-cell RNA sequencing analysis on patient-derived organoids revealed that LOX was induced by IL13 in differentiated cells. LOX-overexpressing organoids showed suppressed basal and up-regulated differentiation markers. In addition, LOX overexpression enhanced junctional protein genes and transepithelial electrical resistance. LOX overexpression restored the impaired differentiation and barrier function, including in the setting of IL13 stimulation. Transcriptome analyses on LOX-overexpressing organoids identified an enriched bone morphogenetic protein (BMP) signaling pathway compared with wild-type organoids. In particular, LOX overexpression increased BMP2 and decreased the BMP antagonist follistatin. Finally, we found that BMP2 treatment restored the balance of basal and differentiated cells. CONCLUSIONS: Our data support a model whereby LOX exhibits noncanonical roles as a signaling molecule important for epithelial homeostasis in the setting of inflammation via activation of the BMP pathway in the esophagus. The LOX/BMP axis may be integral in esophageal epithelial differentiation and a promising target for future therapies.

  PublisherDOI

• Winter Storm Uri and the Texas energy failure (USA)

  Edward Elgar Publishing eBooks · 2024-11-12

  book-chapter1st authorCorresponding
  PublisherDOI

Frequent coauthors

• Lauren Dutcher

  University of Pennsylvania

  75 shared

• Ebbing Lautenbach

  68 shared

• Leigh Cressman

  64 shared

• Kathleen Degnan

  University of Pennsylvania

  61 shared

• Valerie Cluzet

  Vassar Brothers Medical Center

  55 shared

• Trevor Van Schooneveld

  Nebraska Medical Center

  49 shared

• Margaret A. Olsen

  University of Pittsburgh

  44 shared

• Mohamad G. Fakih

  44 shared

Labs

• Hamilton laboratoryPI

Education

• Postdoctoral fellowship, Medicine, Gastroenterology Division

  University of Pennsylvania Perelman School of Medicine

  2013

• PhD, Cell and Molecular Physiology

  University of North Carolina at Chapel Hill

  2010

• BA, Biology

  Assumption College

  2003