Washington University
School of Medicine

Dept. of Pathology & Immunology
Box 8118
660 S. Euclid Ave.
St. Louis, MO 63110

tel: (314) 362-4213
fax: (314) 362-7487
email: jmills@wustl.edu
web: Personal Weblink

My laboratory works on stomach epithelial stem cells. The gastric epithelium in mice and humans renews continuously throughout adult life. It is organized into thousands of invaginations known as glands or gastric units. The gastric epithelial stem cell, which resides in the mid-portion of each unit spawns 5 separate cell lineages, each with a distinct temperospatial pattern of migration and differentiation. Our goals are to delineate the molecular pathways dictating gastric stem cell proliferation and differentiation. We have recently shown that RNA localizing proteins critical for early fly development (e.g., Staufen) are important in normal gastric epithelial differentiation as well. We also study notch, runx, and TGFβ in regulation of gastric stem cells.

Aberrations in stomach renewal occur frequently, ranging from mild side-effects of ingestion of therapeutic agents to gastric carcinoma, the second most deadly cancer worldwide. Our research goals also include elucidating aberrations in stomach organization during disease. We study a model of gastric tumorigenesis that involves transdifferentiation of an expanded glandular progenitor cell into an endocrine carcinoma (with expression of transcription factors such as sox2 and neuroD1) as it invades surrounding tissue and metastasizes to distant organs. The lab uses a multi-disciplinary approach, including: 1) developing and adapting bioinformatics tools that annotate and compare gut stem cell gene expression profiles to those of other tissues, 2) refining techniques for retrieving picogram levels of RNA from specific cell populations in situ using laser-capture microdissection, 3) developing novel histopathologic and immunohistologic techniques to image cells and tissues.

Mills JC, Andersson N, Stappenbeck TS, Chen CC, Gordon JI: Molecular characterization of mouse gastric zymogenic cells. J Biol Chem 278: 46138-46145, 2003.

Mills JC, Andersson N, Hong CV, Stappenbeck T, Gordon JI: Molecular characterization of mouse gastric epithelial progenitor cells. Proc Natl Acad Sci USA 99: 14819-14824, 2002.

Mills JC, Syder AJ, Hong CV, Guruge JL, Raaii F, Gordon JI: A molecular profile of the mouse gastric parietal cell with and without exposure to Helicobacter pylori. Proc Natl Acad Sci USA 98: 13687-13692, 2001.

Mills JC, Roth KA, Cagan RL, Gordon JI: DNA microarrays and beyond: completing the journey from tissue to cell. Nature Cell Biol 3: 175-178, 2001.

Mills JC Gordon JI: A new approach for filtering noise from high-density oligonucleotide microarray datasets. Nucleic Acids Res 29: e72, 2001.