SITE SEARCH


Research > Faculty By Clinical Interest > Thaddeus Stappenbeck, MD, PhD

Professor, Pathology and Immunology
Professor, Developmental Biology
Room 1029, CSRB, North Tower
Office: (314) 362-4214
Lab: (314) 362-4249
E-mail: stappenb@wustl.edu
Publication List

Research

We study the role and regulation of intestinal epithelial stem cells in health and disease. Numerous common, western world maladies (ranging in morbidity from irritable bowel syndrome to colon cancer) target these cells and effect repair, regeneration and transformation of this epithelium. These progenitors compose one of the largest populations of epithelial stem cells in the human body and are the source of the rapid and continuous renewal of the absorptive epithelial lining of the intestine. Our goal is to define their molecular properties and determine how they interact with the surrounding mesenchymal stem cell niche.

We use the mouse intestine (morphologically and developmentally homologous to human intestine) as an in vivo system to model disruptions in both stem cells and their niche. An advantage of intestine for the study of stem cell biology is that both the morphologic features and anatomic location of the epithelial progenitors and their descendant lineages are well established. Thus, well characterized 'micro-geographic' features allow us to collect and analyze specified cell populations using laser capture microdissection (LCM). We use combinations of genetic, pharmacologic and luminal manipulations to test hypotheses about epithelial stem cell function. For example, we have shown that chemically wounding the colon induces activated macrophages to appose epithelial progenitors, thereby supporting proliferation in the stem cell compartment. We are currently investigating the molecular nature of the macrophage-stem cell interaction. In another project, we are pursuing new markers of intestinal epithelial stem cells using the novel genes identified through sequencing micro-cDNA libraries of LCM procured progenitors.

Service to the Department

PresentAutopsy pathology

DBBS Graduate Program Affiliation

Developmental Biology Program
Molecular Cell Biology Program
Immunology Program

Clinical Interest

Anatomic and Molecular Pathology - Autopsy Pathology

Selected Publications

Geske MJ, Zhang X, Patel KK, Ornitz DO, Stappenbeck TS. Fgf9 signaling regulates small intestinal elongation and mesenchymal development. Development. In Press, 2008

Mahoney ZX, Stappenbeck TS, Miner JH. Laminins regulate epithelial cell behavior and maintain crypt-villus architecture in the mouse intestine. J Cell Science; In Press, 2008

Doherty JM, Geske MJ, Stappenbeck TS, Mills, JC. Diverse adult tissue stem cells share specific higher-order patterns of gene expression. Stem Cells; Epub ahead of print, 2008

Kang, S.S., S.M. Bloom, L. Norian, M.J. Geske, R.A. Flavell, T.S. Stappenbeck, P.M. Allen. An antibiotic-responsive mouse model of fulminant ulcerative colitis. PLoS Med. 5:e41, 2008

Brown S.L., T.E. Riehl, M.R. Walker, M.J. Geske, J.M. Doherty, W.F. Stenson and T.S. Stappenbeck. Myd88-dependent positioning of Ptgs2-expressing stromal cells maintains colonic epithelial proliferation during injury. Clin. Invest. 117:258-269, 2007

Ramsey VG, Doherty JM, Chen CC, Stappenbeck TS, Konieczny SF, Mills JC. The maturation of mucus-secreting gastric epithelial progenitors into digestive-enzyme secreting zymogenic cells requires Mist1. Development. 2007 Jan;134(1):211-222, 2007 Abstract

Zhang X, Stappenbeck TS, White AC, Lavine KJ, Gordon JI, Ornitz DM. Reciprocal epithelial-mesenchymal FGF signaling is required for cecal development. Development 133:173-180, 2006 Abstract

Giannakis M, Stappenbeck TS, Mills JC, Leip DG, Lovett M, Clifton SW, Ippolito JE, Glasscock JI, Aru. Molecular properties of adult mouse gastric and intestinal epithelial progenitors in their niches. J Biol Chem 281:11292-11309, 2006 Abstract

Pull SL, Doherty JM, Mills JC, Gordon JI, Stappenbeck TS. Activated macrophages are an adaptive element of the colonic epithelial progenitor niche necessary for regenerative responses to injury. Proc Natl Acad Sci USA 102:99-104, 2005 Abstract

Pull, S.L., J.M. Doherty, J.C. Mills, J.I. Gordon, and T.S. Stappenbeck. Activated macrophages are an adaptive element to the colonic epithelial progenitor niche necessary for regenerative responses to injury. Proc. Natl. Acad. Sci. USA 102:99-104, 2005

Stappenbeck TS, Mills JC, Gordon JI. Molecular features of adult mouse small intestinal epithelial progenitors. Proc Natl Acad Sci USA 100:1004-1009, 2003 Abstract

Stappenbeck TS, Hooper LV, Manchester JK, Wong MH, Gordon JI. Laser capture microdissection of the mouse intestine: Characterizing mRNA and protein expression, and profiling intermediary metabolism in specified cell populations. Methods Enzymol 356:167-196, 2002 Abstract

Stappenbeck TS, Hooper LV, Gordon JI. Developmental regulation of intestinal vasculogenesis by indigenous microbes via Paneth cells. Proc Natl Acad Sci USA 99:15451-15455, 2002 Abstract

Stappenbeck TS, Gordon JI. Extranuclear sequestration of phospho- N-terminal kinase and distorted villi produced by activated Rac1 in the intestinal epithelium of chimeric mice. Development 128:2603-2614, 2001 Abstract

Stappenbeck TS, Gordon JI. Rac1 mutations produce aberrant epithelial differentiation in the developing and adult mouse small intestine. Development 127:2629-2642, 2000 Abstract

Brown SL, Riehl TE, Walker MR, Geske MJ, Doherty JM, Stenson WF, Stappenbeck TS.. Myd88-dependent positioning of Ptgs2-expressing stromal cells maintains colonic epithelial proliferation during injury. J Clin Invest. Jan;117(1):258-69., 2007 Abstract


Current Trainees

Seth Bloom
Clara Moon
Khushbu Patel
Monica Walker