Biomedical Graduate Studies

Description of Research Expertise

Research Interests:
The gut epithelium acts as an arbiter between harmful substances in the external environment and the human body. The Hamilton laboratory specializes in understanding mechanisms regulating the gut epithelium in health and disease. We use in vivo models and patient-derived organoids to understand the molecular basis of intestinal regeneration including in inflammatory bowel disease (IBD). Our studies span three interrelated themes: 1) Defining how RNA binding proteins impart global, post-transcriptional regulation of key pathways in gut physiology and pathophysiology, 2) Evaluating how epithelial stem cell in patients with chronic gastrointestinal diseases behave differently than non-disease stem cells as a basis for stem cell targeted therapies to heal the gut epithelium, and 3) Exploring fundamental intestinal epithelial biology through the study of organoids from patients with rare, monogenic forms of IBD.

Keywords:
gastrointestinal biology, RNA binding proteins, epitranscriptomics, inflammatory bowel disease (IBD), organoids (enteroids/colonoids), post-transcriptional gene regulation, intestinal stem cells

Research Details:
Our laboratory incorporates molecular and cellular biology together with mammalian physiology/pathophysiology and human organoid biology. Techniques employed in the laboratory include tissue culture (2D and 3D, including human organoid models), live cell microscopy, molecular biology, histological analyses, flow cytometry, in vivo transgenic and disease models, single cell transcriptomics and chromatin accessibility analyses, and epitranscriptomics (m6A-seq and other RNA biochemical analyses). Dr. Hamilton is Co-founder and Co-Director of the CHOP Gastrointestinal Epithelium Modeling (GEM) Program (https://www.chop.edu/centers-programs/gastrointestinal-epithelium-modeling-gem-program#supportedresearch), which resides within the Hamilton lab suite in the CHOP Abramson Research Building. The GEM Program serves as a hub for patient-focused gastrointestinal organoid research and connects scientists across the Penn-CHOP campus and nationally to foster community and collaborations. The GEM Core was launched in 2024 at part of the CHOP Research Institute and the Penn P30 Center for Molecular Studies in Digestive and Liver Diseases (https://www.med.upenn.edu/CMSDLD/gastrointestinal-epithelium-modeling-gem-core.html)

Rotation Projects:
1) Evaluate how intestinal epithelial mitophagy pathways prevents cell death in facultative stem cells
2) Define how inflammatory and other environmental factors alter functional outcomes in epithelial stem cells in celiac disease
3) Explore the epigenetic basis for altered progenitor cell states in chronic inflammatory diseases of the gut

Lab Personnel:
Emily McMillan, MS, Lab Manager
Shaneice Nettleford, PhD, Postdoctoral researcher
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
Ian Yannuzzi, BS, CAMB/Cancer Biology PhD student
Yusen Zhou, PhD, Bioinformatician
Heidi Winters, BS, Research specialist
Tatiana Karakesheva, PhD, Research Scientist, Associate Director, CHOP Gastrointestinal Epithelium Modeling (GEM) Program
Bella Peterson, BS, Lab Technician, Gastrointestinal Epithelium Modeling (GEM) Program