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), 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) Evaluating "autophagic plasticity" in intestinal epithelial cells using mouse models and organoids; autophagic plasticity in human inflammatory bowel disease.
2) Defining epithelial cell memory in response to inflammation using mouse models and organoids.
3) Defining how mutations in the RNA exosome contribute to intestinal epithelial cell dysfunction in very early onset inflammatory bowel disease.
4) Evaluating aberrations Crohn's disease stem cells in pediatric and adult patients using single cell multi-omics and functional organoid assays.


Lab Personnel:
Kaitlyn Naughton, BS, Lab Technician
Emily McMillan, MS, Lab Manager
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
Noor Nema, MD, CHOP GI fellow
Gloria Soto, BS, Lab Technician, Gastrointestinal Epithelium Modeling (GEM) Program
Kay Katada, BS, CAMB/Cell Biology, Physiology, and Metabolism PhD student

Selected Publications

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 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 September 2022.

Nicolette M. Johnson*, Louis R. Parham*, Jeeyoon Na, Kaitlyn E. Monaghan, Hannah M. Kolev, Alena Klochkova, Melissa S. Kim, Charles H. Danan, Zvi Cramer, Lauren A. Simon, Kaitlyn E. Naughton, Stephanie Adams-Tzivelekidis, Youjen Tian, Patrick A. Williams, Simone Sidoli, Kelly A. Whelan, Ning Li, Christopher J. Lengner**, Kathryn E. Hamilton**: Autophagic state prospectively identifies facultative stem cells in the intestinal epithelium. EMBO Reports September 2022.

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 September 2022.

Oxana Dmitrieva-Posocco, Andrea C. Wong, Patrick Lundgren, Aleksandra M. Golos, Hélène C. Descamps, Lenka Dohnalová, Zvi Cramer, Yuhua Tian, Brian Yueh, Onur Eskiocak, Gabor Egervari, Yemin Lan, Jinping Liu, Jiaxin Fan, Jihee Kim, Bhoomi Madhu, Kai Markus Schneider, Svetlana Khoziainova, Natalia Andreeva, Qiaohong Wang, Ning Li, Emma E. Furth, Will Bailis, Judith R. Kelsen, Kathryn E. Hamilton, Klaus H. Kaestner, Shelley L. Berger, Jonathan A. Epstein, Rajan Jain, Mingyao Li, Semir Beyaz, Christopher J. Lengner, Bryson W. Katona, Sergei I. Grivennikov, Christoph A. Thaiss, Maayan Levy: Beta-hydroxybutyrate suppresses colorectal cancer. Nature May 2022.

Mohammad Faujul Kabir1, Adam Karami1, Ricardo Cruz-Acuna, Alena Klochkova, Reshu Saxena, Anbin Mu, Mary Grace Murray, Jasmine Cruz, Annie E. Fuller, Margarette Clevenger, Kumaraswamy Naidu Chitrala, Yin Fei Tan, Kelsey Keith, Jozef Madzo, Hugh Huang, Jaroslav Jelinek, Tatiana Karakasheva, Kathryn E. Hamilton, Amanda B. Muir, Marie-Pier Tetreault, Kelly A. Whelan: Single cell transcriptomic analysis reveals cellular diversity of murine esophageal epithelium and age-associated mitochondrial dysfunction. Nature Communications April 2022 Notes: Accepted March 2022.

Takeo Hara, PhD, Yuta Kasagi, Joshua Wang, Masaru Sasaki1, Bailey Aaron1, Adam Karami, Masataka Shimonosono, Rieko Shimonosono, Hisatsugu Maekawa, Lauren Dolinsky, Benjamin Wilkins, Jeremy Klein, Jane Wei, Kathryn Nunes, Kristle Lynch, Jonathan M. Spergel, Kathryn E. Hamilton PhD, Melanie A. Ruffner, Tatiana A. Karakasheva PhD, Kelly A. Whelan, Hiroshi Nakagawa, Amanda B. Muir: CD73+ epithelial progenitor cells which contribute to homeostasis and renewal are depleted in eosinophilic esophagitis. Cellular and Molecular Gastroenterology and Hepatology December 2021 Notes: In Press.

Tatiana A Karakasheva, Joel T Gabre, Uma M Sachdeva, Ricardo Cruz-Acuña, Eric W Lin, Maureen DeMarshall, Gary W Falk, Gregory G Ginsberg, Zhaohai Yang, Michele M Kim, Eric S Diffenderfer, Jason R Pitarresi, Jinyang Li, Amanda B Muir, Kathryn E Hamilton, Hiroshi Nakagawa, Adam J Bass, Anil K Rustgi: Patient-derived organoids as a platform for modeling a patient's response to chemoradiotherapy in esophageal cancer. Scientific Reports October 2021.

Jodie Ouahed, Judith R. Kelsen, Waldo A. Spessott, Kameron Kooshesh, Maria L. Sanmillan, Noor Dawany, Kathleen E. Sullivan, Kathryn Hamilton, Voytek Slowik, Sergey Nejentsev, João Farela Neves, Helena Flores, Wendy K. Chung, Ashley Wilson, Kwame Anyane Yeboa, Karen Wou, Preti Jain, Michael Field, Sophia Tollefson, Dalin Li1, Dermot P.B. McGovern, Daniel Kotlarz, Christoph Klein, Jonathan Evans, Neil Warner, Abdul Elkadri, Aleixo M. Muise, Jeffrey Goldsmith, Agnes Toth-Petroczy, Dana Vuzman, Nikkola Carmichae, Corneliu Bodea, Christopher A. Cassa, Marcella Devoto, Richard L. Maas, Edward M. Behrens, Claudio G. Giraudo, and Scott B. Snapper: Variants in STXBP3 Result in Very Early Onset Inflammatory Bowel Disease, Bilateral Sensorineural Hearing Loss and Immune Deficiency Journal of Crohn's and Colitis February 2021 Notes: accepted 2.12.21.

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 January 2021.

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Last updated: 09/28/2022
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