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) Define how mutations in the RNA exosome contribute to intestinal epithelial cell dysfunction in very early onset inflammatory bowel disease.
2) 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


Lab Personnel:
Kaitlyn Naughton, BS, Lab Technician
Emily McMillan, MS, Lab Manager
Xianghui Ma, PhD, Postdoctoral fellow
Shaneice Nettleford, PhD, Postdoctoral fellow
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
Yusen Zhou, PhD, Bioinformatician