Linda Samuelson, PhD

Dr. Samuelson’s research program examines the development and function of epithelial cells in stomach and intestine.  We are interested in how basic developmental pathways, growth factors and immune modulators function to regulate epithelial cell proliferation and differentiation in normal physiology and disease. Our approach is to use genetically engineered mouse models and organ culture systems to interrogate pathways regulating epithelial cell homeostasis.  Recent studies have focused on the importance of Notch signaling for regulating stem and progenitor cells.  In the intestine, we have determined that Notch plays a fundamental role in cell lineage choice between absorptive enterocytes and secretory cell types (goblet, endocrine, Paneth). These studies identified Atoh1 and Neurogenin3 as key transcriptional effectors regulating secretory cell differentiation. More recent findings demonstrate a distinct function for Notch signaling to maintain the intestinal stem cell. We have also shown that Notch regulates cellular proliferation and cell fate determination in the stomach, thus suggesting that this signaling pathway plays a fundamental role for epithelial cell renewal in the gastrointestinal tract.

The Samuelson lab studies the development and function of  the gastrointestinal system, focusing on epithelial cell homeostasis in stomach and intestine. In the gut, stem and progenitor cells continuously generate differentiated cell types to maintain and replenish these tissues. Multiple growth factors and morphogens, such as Notch, Wnt, Hedgehog and gastrin regulate proliferation and epithelial cell specification, although their mechanisms of action are poorly understood. Our current focus is directed to the Notch signaling pathway and its function in tissue homeostasis and regeneration after injury. We have determined that  Notch  directly targets gastrointestinal stem cells to regulate the balance of cellular proliferation vs. differentiation.  We utilize a variety of modern experimental approaches and take advantage of genetically-engineered mouse models, mouse and human organoids and human cancer-derived cell lines to understand fundamental mechanisms of gastrointestinal stem cell function.