Faculty

Kathryn E. Hamilton, PhD

faculty photo
Assistant Professor of Pediatrics
Department: Pediatrics
Graduate Group Affiliations

Contact information
902F Abramson Research Center
3615 Civic Center Blvd
Children's Hospital of Philadelphia
Philadelphia, PA 19104
Lab: 267-426-5266
Education:
BA (Biology)
Assumption College, 2003.
PhD (Cell and Molecular Physiology)
University of North Carolina Chapel Hill, 2010.
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Description of Research Expertise

Research Interests: The gut epithelium acts as an arbiter between harmful substances in the external environment and the human body. Our laboratory specializes in understanding mechanisms regulating the gut epithelium in health and disease. We use in vivo models and mouse/human 3D enteroid and colonoid (organoid) lines to understand the molecular basis of intestinal regeneration and inflammatory bowel disease (IBD). Within these contexts, we are interested in how RNA binding proteins impart global, post-transcriptional regulation of key pathways in normal physiology and pathophysiology.

Keywords: gastrointestinal biology, RNA binding proteins, inflammatory bowel disease (IBD), organoids (enteroids/colonoids), in vivo models

Research Details:

1) Post-transcriptional gene regulation is essential to maintain homeostasis in highly proliferative tissues such as the gastrointestinal epithelium. Gastrointestinal epithelial cells must interface with and process signals from the food we eat, our microbiota, and resident immune and stromal cells- all while maintaining a physical barrier between the luminal contents and underlying tissue. Our lab seeks to understand how post-transcriptional gene regulation helps orchestrate the complex roles of gastrointestinal epithelial cells with the goal of generating foundational knowledge for the development of new therapeutic targets in human disease. To this end, our laboratory incorporates training in molecular and cellular biology and physiology/pathophysiology. Techniques employed in the laboratory include tissue culture (2D and 3D, including human organoid models), live cell microscopy, molecular biology, immunohistochemistry, flow cytometry, in vivo transgenic and disease models, and more recently, single cell transcriptomics and other RNA biology techniques. Finally, we embarked recently upon a new area of study for the lab- understanding how the RNA binding protein IMP1's function as a reader of m6A-modified mRNAs contributes to gastrointestinal health and disease.

2) Our lab is interested in how intestinal epithelial stem cells behave in regeneration and disease- specifically IBD. We use 3D organoids from patients to identify how epithelial stem cell behavior is altered in patients with novel IBD gene variants. To support this exciting work, Dr. Hamilton is Co-Director of the CHOP Gastrointestinal Epithelium Modeling (GEM) Program, which resides within the Hamilton lab suite. The GEM Program serves as a hub for patient-focused gastrointestinal organoid research and connects scientists across the Penn-CHOP campus to foster community and collaborations.

Rotation Projects:
1) Evaluating how IMP1 regulation of the autophagy pathway contributes to stemness/cellular plasticity in response to food additives using mouse models and organoids
2) Defining epithelial cell "memory" in response to inflammation using mouse models and organoids
3) Dry-bench/remote project: Defining transcriptional differences between healthy and IBD patient-derived organoids (project will be in collaboration with lab bioinformatician; project focus is on data interpretation and manuscript development)

Lab Personnel:
Lauren Simon, BS, Laboratory manager
Patrick Williams, PhD, Postdoctoral fellow
Xianghui Ma, PhD, Postdoctoral fellow
Louis Parham, BS, CAMB/Cancer Biology PhD student
Charles Danan, BS, CAMB/Genetics and Epigenetics MD/PhD student
Tatiana Karakesheva, PhD, Research Associate, Gastrointestinal Epithelium Modeling (GEM) Program
Brooker Boyer, MD, CHOP GI fellow

Selected Publications

Sarah A. Smith,1 Sayaka A. Ogawa,1 Lillian Chau,1 Kelly A. Whelan,2 Kathryn E. Hamilton,3 Jie Chen,4 Lu Tan,4 Eric Z. Chen,5,12 Sue Keilbaugh,1 Franz Fogt,6 Meenakshi Bewtra,1 Jonathan Braun,7 Ramnik J. Xavier,8,9 Clary B. Clish,8 Barry Slaff,10 Aalim M. Weljie,10 Frederic D. Bushman,11 James D. Lewis,1,12 Hongzhe Li,12 Stephen R. Master,4 Michael J. Bennett,4,6 Hiroshi Nakagawa,13 and Gary D. Wu1: Mitochondrial dysfunction alters intestinal epithelial metabolism of hepatic acylcarnitines Journal of Clinical Investigation 131, January 2021.

Judith R. Kelsen, Noor Dawany, Maire A. Conrad, Tatiana Karakasheva, Kelly Maurer, Jane M. Wei, Selen Uman, Maiah H. Dent, Rithika Behera, Laura M. Bryant, Xianghui Ma, Leticia Moreira, Priya Chatterji, Rawan Shraim, Audrey Merz, Rei Mizuno, Lauren A. Simon, Amanda B. Muir, Claudio Giraudo, Edward M. Behrens, Kelly A. Whelan, Marcella Devoto, Pierre A. Russo, Sarah F. Andres, Kathleen E. Sullivan, Kathryn E. Hamilton: Colonoids from patients with pediatric inflammatory bowel disease exhibit decreased growth associated with inflammation severity and durable upregulation of antigen presentation genes. Inflammatory Bowel Diseases June 2020 Notes: In Press.

Hiroshi Nakagawa, Yuta Kasagi, Tatiana A. Karakasheva, Takeo Hara, Bailey Aaron, Takashi Kijima, Veronique Giroux, Dominique Bailey, Benjamin Wilkins, Julian A. Abrams, Gary W. Falk, Seema Aceves, Jonathan M. Spergel, Kathryn E. Hamilton, Kelly A. Whelan, Amanda Muir: Modeling epithelial homeostasis and reactive epithelial changes in human and murine three-dimensional esophageal organoids. Current Protocols in Stem Cell Biology February 2020 Notes: In Press.

Sarah F. Andres, Kathy N. Williams, Rei Mizuno, Jeff Headd, Priya Chatterji, Kathryn E. Hamilton, Anil K. Rustgi: IMP1 3’ UTR shortening enhances metastatic burden in colorectal cancer. Carcinogenesis 40(4): 569-579, June 2019.

Priya Chatterji, Patrick A. Williams, Kelly A. Whelan, Fernando C. Samper, Sarah F. Andres, Lauren A. Simon, Louis R Parham, Rei Mizuno, Emma T. Lundsmith, David S.M. Lee, Shun Liang, H.R. Sagara Wijeratne; Stefanie Marti, Lillian Chau, Veronique Giroux, Benjamin J. Wilkins, Gary D. Wu, Premal Shah, Gian G. Tartaglia, and Kathryn E. Hamilton: Posttranscriptional regulation of colonic epithelial repair by RNA binding protein IMP1/IGF2BP1. EMBO Reports 20(6): e47074, June 2019.

Priya Chatterji*, Kathryn E. Hamilton*, Shun Liang, Sarah F. Andres, H. R. Sagara Wijeratne, Rei Mizuno, Lauren A. Simon, Philip D. Hicks, Shawn W. Foley, Jason R. Pitarresi, Andres J. Klein-Szanto, Amanda T. Mah, Laurianne Van Landeghem, Brian D. Gregory, Christopher J. Lengner, Blair B. Madison, Premal Shah, and Anil K. Rustgi *co-first author: The LIN28B-IMP1 post-transcriptional regulon has opposing effects on oncogenic signaling in the intestine. Genes and Development 32(15-16): 1020-1034, August 2018.

Véronique Giroux, Julien Stephan, Priya Chatterji, Ben Rhoades, Andres J. Klein-Szanto, Christopher J. Lengner, Kathryn E. Hamilton, Anil K. Rustgi: Mouse intestinal krt15+ crypt cells are radio-resistant and tumor-initiating. Stem Cell Reports 10(6): 1947-1958, June 2018.

Rei Mizuno, Priya Chatterji, Sarah F. Andres, Kathryn E. Hamilton, Lauren A. Simon, Shawn Foley, Arjun Jeganathan, Brian Gregory, Blair B. Madison, and Anil K. Rustgi : Differential regulation of LET-7 by LIN28B isoform-specific functions. Molecular Cancer Research 16(3): 403-416, March 2018.

Yuta Kasagia, Prasanna M. Chandramouleeswarana, Kelly A. Whelan, Koji Tanaka, Veronique Giroux, Medha Sharma, Joshua Wang, Alain J. Benitez, Maureen DeMarshall, John W. Tobias, Kathryn E. Hamilton, Gary W. Falk, Jonathan M. Spergel, Andres J. Klein-Szanto, Anil K. Rustgi, Amanda B. Muirb, Hiroshi Nakagawa: The esophageal organoid system reveals functional interplay between Notch and cytokines in reactive epithelial changes. Cell and Molecular Gastroenterology 5(3): 333-352, January 2018.

Kelly A Whelan, Jamie F Merves, Veronique Giroux, Koji Tanaka, Andy Guo,Prasanna M Chandramouleeswaran,, Alain J Benitez, Kara Dods, Jianwen Que, Joanne C Masterson, Shahan D Fernando, Bridget C Godwin, Andres J Klein-Szanto, Kudakwashe Chikwava, Eduardo D Ruchelli, Kathryn E Hamilton, Amanda B Muir, Mei-Lun Wang, Glenn T Furuta, Gary W Falk, Jonathan M Spergel, Hiroshi Nakagawa: Autophagy mediates epithelial cytoprotection in eosinophilic oesophagitis. Gut 66(7): 1197-1207, July 2017.

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Last updated: 01/26/2021
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