Areas of Interest
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.
Lopez-Diaz, L., R. Jain, T.M. Keeley, K.L. VanDussen, C.S, Brunkan, D.L. Gumucio, and L.C. Samuelson. Intestinal neurogenin 3 directs differentiation of a bipotential secretory progenitor to endocrine cell rather than goblet cell fate. Dev. Biol. 309:298-305 (2007).
Qiao, X.T., J.W Ziel, W. McKimpson, B.B. Madison, A. Todisco, J.L. Merchant, L.C. Samuelson, and D.L. Gumucio. Prospective identification of a multilineage progenitor in murine stomach epithelium. Gastroenterology 133:1989-98 (2007).
Jain, R.N., A.A. Al-Menhali, T.M. Keeley, J. Ren, M. El-Zatari, X. Chen, J.M. Merchant, T.S. Ross, C.S. Chew, L.C. Samuelson. Hip1r is expressed in gastric parietal cells and is required for tubulovesicle formation and cell survival in mice. J. Clin. Invest. 118:2459-70 (2008).
VanDussen, K.L. and L.C. Samuelson. Mouse atonal homology 1 directs intestinal progenitors to secretory cell rather than absorptive cell fate. Dev. Biol. 346:215-23 (2010).
Keeley, T.M. and L.C. Samuelson. Cytodifferentiation of the postnatal mouse stomach in normal and Huntingtin Interacting Protein 1 related (Hip1r)-deficient mice. Amer. J. Physiol-Gastrointest. Liver Physiol. 299:G1241-51 (2010).
Liu, Z., E.S. Demitrack, T.M. Keeley, K.A. Eaton, M. El-Zaatari, J.L. Merchant and L.C. Samuelson. IFN contributes to the development of gastric epithelial cell metaplasia in Huntingtin Interacting Protein 1 Related (Hip1r)-deficient mice. Lab Invest 92:1045-1057 (2012).
VanDussen, K.L., A. J. Carulli, T.M. Keeley, S.R. Patel, B.J. Puthoff, S.T. Magness, I.T. Tran, I. Mallard, C. Siebel, A. Kolterud, A. Grosse, D.L. Gumucio, S.A. Ernst, Y-H Tsai, P. Dempsey and L.C. Samuelson. Notch signaling modulates proliferation and differentiation of intestinal crypt base columnar stem cells. Development 139:488-497 (2012).
Honors & Awards
2011 John A. Williams Collegiate Professorship in Gastrointestinal Physiology
2012 Shanghai Cancer Forum Award, Chinese Society of Clinical Oncology
2012 Excellence in Mentorship Award, Program in Biomedical Sciences, University of Michigan
2013 Takeda Distinguished Scientist Award, American Physiological Society
2014 Morton I. Grossman Award for Gastrointestinal Research, Am. Gastroenterological Assoc.
B.S. Michigan State University; Ph.D., University of Chicago, 1984