Alumnus Speaker at the 2003 MSTP Retreat

Thaddeus Stappenbeck, M.D., Ph.D.

I graduated from the Medical Scientist Training Program at Northwestern University in 1995 and am the Alumni Speaker at the 2003 MSTP Retreat on August 17-18, 2003. Currently I am an Assistant Professor of Pathology at Washington University School of Medicine in St. Louis.

Research Interests

The adult human gut contains one of the largest continually active populations of epithelial stem cells in the body. Defining the molecular properties of these cells and their surrounding mesenchymal niche in both normal and pathologic states will offer new insights into diseases that affect repair, regeneration and transformation of this epithelium. I use the mouse intestine as an in vivo experimental system, since the cell biological features of epithelial progenitors and their descendant lineages have homologous features to those found in the human gut. An advantage of intestine for the study of stem cell biology is that both the morphologic features and anatomic location of the epithelial progenitors are well established. However, molecular markers and key signaling pathways that determine gut epithelial stem cell selection and function are still not known. To address this issue, I have begun to develop transcription profiles of epithelial stem cells from different regions of the mouse gut. In order to collect epithelial stem cells for analysis, I use the advantageous micro-anatomy in combination with either genetic or pharmacologic manipulations that act to consolidate epithelial progenitors so that they can be physically retrieved from tissue sections by laser capture microdissection. Functional genomics studies (using both cDNA microarrays and sequencing normalized cDNA libraries) of cells harvested in this manner provide molecular profiles of epithelial progenitors within their niche from different regions of the gut. The comparison of gut stem cell profiles to databases generated from other tissue resident stem cells, such as the hematopoetic and neural systems reveals key similarities of specific pathways and processes. Among them, components of c-myc signaling pathways, as well as RNA binding proteins involved in transcript processing, localization, and translation are prominently represented. In addition, many lesser characterized transcriptional regulatory elements and cell surface molecules that are enriched in these cells should provide additional new tools to study this population of cells and their alteration in different types of intestinal pathology.

Recent Publications

Stappenbeck, T.S., Mills, J.C., and Gordon, J.I. 2003. Molecular features of adult mouse small intestinal epithelial progenitors. Proc. Natl. Acad. Sci. USA. 100, 1004-1009.

Mills, J.C., Anderson, N.,Hong, C.V., Stappenbeck, T.S., and Gordon, J.I. 2002. Molecular characterization of mouse gastric epithelial progenitor cells. Proc. Natl. Acad. Sci. USA 99, 14819-14824.

Stappenbeck, T.S., Hooper, L.V., Manchester, J.K., Wong, M.H., and Gordon, J.I. 2002. Laser capture microdissection of the mouse intestine: Characterizing mRNA and protein expression, and profiling intermediary metabolism in specified cell populations. In: Methods in Enzymology (Laser Capture Microscopy and Microdissection, P.M. Conn, editor) Academic Press. 356, 168-196.