Kathryn E. Hamilton, PhD
3615 Civic Center Blvd
Children's Hospital of Philadelphia
Philadelphia, PA 19104
Assumption College, 2003.
PhD (Cell and Molecular Physiology)
University of North Carolina Chapel Hill, 2010.
Description of Research ExpertiseResearch Interests: The Hamilton laboratory specializes in understanding mechanisms regulating gut homeostasis in health and disease, with a specific interest in epithelial cell responses to damage and inflammation. We employ in vivo models and primary, three-dimensional enteroid and colonoid cultures from mice and humans to understand the molecular basis of intestinal regeneration, inflammatory bowel disease (IBD) and colorectal cancer. 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), colorectal cancer, organoids (enteroids/colonoids), in vivo models
Research Details: Our laboratory incorporates training in cell biology, physiology/pathophysiology, and molecular genetics to understand basic mechanisms in human disease, providing foundations for new biomarkers or therapeutic targets. Techniques employed in the laboratory include tissue culture (2D and 3D), molecular biology, microscopy, immunohistochemistry, flow cytometry and in vivo disease models. New techniques being incorporated into the laboratory in the coming months include transcriptomics, ribonomics, and proteomics to understand global changes in the context of deleting or overexpressing RNA binding proteins. Based upon recent studies identifying the RNA binding protein IMP1 as a reader of m6A-modifed mRNAs, we are now utilizing our unique Imp1 knockout and over-expression mouse models to explore RNA modifications in gastrointestinal disease contexts.
1) Evaluating how inflammatory cytokines regulate the expression and functional roles of IMP1
2) Determining how IMP1 acts as a "reader" of m6A-methylated transcripts in normal colon and in patients with Inflammatory Bowel Disease
3) Evaluating the effect of novel genetic variants in epithelial stem cells from patients with pediatric and Very Early Onset (VEO) Inflammatory Bowel Disease
Lauren Simon, BS, Laboratory manager
Patrick Williams, PhD, Postdoctoral fellow
Xianghui Ma, PhD, Postdoctoral fellow
Louis Parham, BS, CAMB/Cancer Biology PhD student
Maiah Dent, BS, Research specialist
Selected PublicationsSarah 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.
Véronique Giroux, Ashley A. Lento, Mirazul Islam, Jason R. Pitarresi, Akriti Kharbanda, Kathryn E. Hamilton, Kelly A. Whelan, Apple Long, Ben Rhoades, Qiaosi Tang, Hiroshi Nakagawa, Christopher J. Lengner, Adam J. Bass, E. Paul Wileyto, Andres J. Klein-Szanto, Timothy C. Wang, and Anil K. Rustgi: Long-lived keratin 15+ esophageal progenitor cells contribute to homeostasis and regeneration. Journal of Clinical Investigation 127(6): 2378-2391, June 2017.
Dana Almohazey, Yuan-Hung Lo, Claire Vossler, Alan Simmons, Jonathan Hsieh, Edie Bucar, Michael Schumacher, Kathryn Hamilton, Ken Lau, Noah Shroyer, Mark Frey: The ErbB3 receptor tyrosine kinase negatively regulates Paneth cells by PI3K-dependent suppression of Atoh1. Cell Death and Differentiation 24(5): 855-865, May 2017.
Ravi K. Amaravadi, Kathryn E. Hamilton, Xiaohong Ma, Shengfu Piao, Armando Del Portillo, Katherine L. Nathanson, Matteo S. Carlino, Georgina V. Long, Igor Puzanov, Xiaowei Xu, Jennifer J.D. Morrissette, Kenneth Y. Tsai, Keith T. Flaherty, Jeffrey A. Sosman, Grant R. Goodman, Grant A. McArthur, Anil K. Rustgi, David C. Metz, Lynn M. Schuchter, Paul B. Chapman, and Antonia R. Sepulveda: Multiple gastrointestinal polyps in patients treated with BRAF inhibitors. Clinical Cancer Research 21(23): 5215-21, December 2015.