Kathryn (Kate) Hamilton, PhD

faculty photo
Assistant Professor of Pediatrics (Gastroenterology, Hepatology and Nutrition)
Faculty, Institute for Translational Medicine and Therapeutics (ITMAT), University of Pennsylvania School of Medicine
Faculty, Institute for Regenerative Medicine (IRM), University of Pennsylvania School of Medicine
Co-Director, Gastrointestinal Epithelial Modeling Program, Children's Hospital of Philadelphia
Co-Leader, Intestinal Biology Theme, NIH/NIDDK P30 Center for Molecular Studies in Digestive and Liver Diseases, University of Pennsylvania School of Medicine
Department: Pediatrics
Graduate Group Affiliations

Contact information
Children's Hospital of Philadelphia
3615 Civic Center Blvd
902F Abramson Research Center
Philadelphia, PA 19104
Lab: 267-426-5266
Education:
B.A. (Biology)
Assumption College, 2003.
Ph.D. (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), post-transcriptional gene regulation
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) Evaluate aberrations in Crohn's disease stem cells in the pediatric to adult continuum using single cell multi-omics and functional organoid assays.
3) Define the contribution of the m6A/Mettl3/Igf2bp1 axis to epithelial stem cell responses to stress and tissue damage


Lab Personnel:
Emily McMillan, MS, Lab Manager
Xianghui Ma, PhD, Postdoctoral researcher
Shaneice Nettleford, PhD, Postdoctoral researcher
Virginia Saurman, DO, CHOP GI fellow
Kay Katada, BS, CAMB/Cell Biology, Physiology, and Metabolism PhD student
Daana Roach, BS, DVM-PhD student, CAMB/Developmental, Stem Cell, and Regenerative Biology PhD student
Olivia Hix, BS, DVM-PhD student, CAMB/Developmental, Stem Cell, and Regenerative Biology PhD student
Yusen Zhou, PhD, Bioinformatician
Tatiana Karakesheva, PhD, Research Scientist, Associate Director, CHOP Gastrointestinal Epithelium Modeling (GEM) Program
Erin Gilbert, BS, Lab Technician, Gastrointestinal Epithelium Modeling (GEM) Program

Selected Publications

Sasaki M, Hara T, Wang JX, Zhou Y, Kennedy KV, Umeweni N, Alston M, Spergel ZC, Ishikawa S, Teranishi R, Nakagawa R, Mcmillan E, Whelan KA, Karakasheva TA, Hamilton KE, Ruffner MA, Muir AB: Lysyl oxidase regulates epithelial differentiation and barrier integrity in eosinophilic esophagitis. Cellular and Molecular Gastroenterology and Hepatology Page: In press, March 2024.

Alena Klochkova, Adam L. Karami, Annie D. Fuller, Louis R. Parham, Surali R. Panchani, Shruthi Natarajan, Jazmyne L. Jackson, Anbin Mu, Yinfei Tan, Kathy Q. Cai, Andres J. Klein-Szanto, Amanda B. Muir, Marie-Pier Tétreault, Kathryn E. Hamilton, Kelly A. Whelan: Autophagy contributes to homeostasis in esophageal epithelium where high autophagic vesicle level marks basal cells with limited proliferation and enhanced self-renewal potential. Cell and Molecular Gastroenterology and Hepatology Page: In press, March 2024.

Louis R. Parham, Patrick A. Williams, Kay Katada, Shaneice K. Nettleford, Priya Chatterji1, Kofi K. Acheampong, Charles H. Danan, Xianghui Ma, Lauren A. Simon, Kaitlyn E. Naughton, Rei Mizuno, Tatiana Karakasheva, Emily A. McMillan, Kelly A. Whelan, Donita C. Brady, Sydney M. Shaffer, Kathryn E. Hamilton : IGF2BP1/IMP1 deletion enhances a facultative stem cell state via regulation of MAP1LC3B. Cellular and Molecular Gastroenterology and Hepatology 17(3): 439-451, December 2023.

Charles H. Danan, Kaitlyn E. Naughton, Katharina E. Hayer, Sangeevan Vellappan, Emily A. McMillan, Yusen Zhou, Rina Matsuda, Shaneice K. Nettleford, Kay Katada, Louis R. Parham, Xianghui Ma, Afrah Chowdhury, Benjamin J. Wilkins, Premal Shah, Matthew D. Weitzman, Kathryn E. Hamilton: Intestinal transit amplifying cells require METTL3 for growth factor signaling and cell survival. JCI Insight 8(23): e171657, October 2023.

Clara Morral, Reem Ghinnagow, Tatiana A. Karakasheva, Yusen Zhou, Anusha E Thadi, Ning Li, Benjamin Yoshor, Gloria E. Soto, Chia-Hui Chen, Daniel Aleynick, Sarah Weinbrom, MaryKate Fulton, Yasin Uzun, Meenakshi Bewtra, Judith R. Kelsen, Christopher J. Lengner, Kai Tan, Andy J. Minn, Kathryn E. Hamilton: Isolation of epithelial and stromal cells from colon tissues in homeostasis and under inflammatory conditions. BioProtocols 13(18): e4825, September 2023 Notes: Featured on issue cover.

Patrick A. Williams, Kaitlyn E. Naughton, Lauren A. Simon, Gloria E. Soto, Louis R. Parham, Xianghui Ma, Charles H. Danan, Weiming Hu, Elliot S. Friedman, Emily A. McMillan; Hritik Mehta, Madison A. Stoltz, Joshua Soto Ocaña, Joseph Zackular, Kyle Bittinger, Kelly A. Whelan, Tatiana A. Karakasheva, Kathryn E. Hamilton: Intestinal epithelial autophagy is required for the regenerative benefit of calorie restriction. American Journal of Physiology-Gastrointestinal and Liver Physiology 324(5): G354-G368, May 2023 Notes: Article was selected for APSselect, a monthly collection from the APS that showcases some of the best recently published articles in physiological research (May 2023).

Tatiana A. Karakasheva, Yusen Zhou, Hongbo M. Xie, Gloria E. Soto, Tiana D. Johnson, Madison A. Stoltz, Daana M. Roach, Noor Nema, Chizoba N. Umeweni, Kaitlyn Naughton, Lauren Dolinsky, James A. Pippin, Andrew D. Wells, Struan F.A. Grant, Louis Ghanem, Natalie Terry, Amanda B. Muir, Kathryn E. Hamilton : Patient-derived colonoids from disease-spared tissue retain inflammatory bowel disease-specific transcriptomic signatures. Gastro Hep Advances 2(6): 830-842, April 2023 Notes: Featured on issue cover.

Madeline Kuhn, Yang Zhang, John Favate, Mayu Morita, Aurora Blucher, Sukanya Das, Shun Liang, Ranjan Preet, Louis R. Parham, Kathy Williams, Sudheer Molugu, Randall Armstrong, Wei Zhang, Jiegang Yang, Kathryn E. Hamilton, Dan Dixon, Gordon Mills, Terry Morgan, Premal Shah, and Sarah F. Andres: IMP1/IGF2BP1 in human colorectal cancer extracellular vesicles. American Journal of Physiology-Gastrointestinal and Liver Physiology 323(6): G571-G585, October 2022.

Sunghee Estelle Park, Shawn Kang, Jungwook Paek, Andrei Georgescu, Jeehan Chang, Alex Yoon, Benjamin J. Wilkins, Tatiana Karakasheva, Kathryn E. Hamilton, Dan Dongeun Huh: Geometric engineering of organoid culture for enhanced organogenesis in a dish. Nature Methods 19(11): 1449-1460, October 2022 Notes: Accompanying News and Views: https://www.nature.com/articles/s41592-022-01656-3.

Cynthia López-Haber, Zachary Hutchins, Xianghui Ma, Kathryn E. Hamilton and Adriana R. Mantegazza: SLC15A4 favors inflammasome function via mTORC1 signaling and autophagy restraint in dendritic cells. EMBO 41(20): e111161, September 2022.

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Last updated: 03/20/2024
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