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. 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