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Faculty > Faculty Alphabetical > Jason Mills, MD, PhDAssistant Professor, Pathology and Immunology
Assistant Director, Molecular Biology and Pharmacology
Room 1030, CSRB - North Tower Annex
Office: (314) 362-4213
Lab: (314) 362-4258
E-mail: jmills@wustl.edu
Pub Med Search |  |
Research
| | My lab is using a multipronged approach to understand the cellular and molecular details of adult stem cell biology in the mouse and human stomach. We study both differentiation from the normal stem cell and how differentiation goes awry in response to inflammation. In particular, we have focused on how mucus-secreting neck cells in the stomach arise and then undergo a dramatic differentiation into digestive-enzyme-secreting zymogenic (chief) cells. This differentiation pathway is a key feature of normal stomach function and homeostasis that is disrupted during the pre-cancerous state of chronic gastric atrophy in humans. We combined mouse genetics, human histopathology and bioinformatic promoter/expression analyses, as well as in vitro mechanistic studies to identify the first gene, the bHLH transcription factor Mist1, required for normal maturation of zymogenic cells, and we have shown that this gene is lost during progression to chronic gastric atrophy. We are investigating the potential targets of Mist1 in regulating this process by analyzing stomachs of adult normal and Mist1 null mice using technologies such as laser-capture microdissection followed by GeneChip and Mass Spectrometry analysis of zymogenic cells. We are also correlating Mist1 expression to histopathologic cancer stage in a pool of human patient samples. Finally, we are determining Mist1 interacting proteins and promoter elements by forced expression of normal and DNA-binding-deficient Mist1 in human gastric cell lines. This approach will yield insights into mechanisms of Mist1 function and roles for its targets in normal and diseased stomachs.
We are extending this work to dissect other potential regulators of stem cell --> neck cell --> zymogenic cell differentiation. We have performed the first comprehensive gene expression profile of neck cells and are analyzing neck cell specific genes to develop markers for tumor progression, promoters to target neck cell-specific expression, and other potential differentiation-regulating factors. These markers will be used to interrogate diseased human stomach biopsies. We are also analyzing the role of BMP and Sonic hedgehog signaling in gastric homeostasis and disease.
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Editorial Responsibilities
| | 2008 - Present | Editorial Board Member | Digestive Diseases and Sciences | | 2008 - Present | Editorial Board Member | American Journal of Physiology: Gastrointestinal and Liver Physiology |
Service to the Department
| | 2009 - Present | Director Research Track Residency Recruitment | | 2004 - Present | Attending Pathologist, Autopsy Service |
Service to the University
| | 2009 - Present | Co-chair, DBBS Admissions Committee | | 2006 - 2006 | Lecturer, Contemporary Molecular Immunology 530 | | 2005 - Present | Lecturer & Lab discussion leader, 2nd year Medical School Pathology Course | | 2005 - 2008 | Discussion Leader, Molecular Cell Biology 5068 | | 2005 - 2005 | Section leader, Biology 5011, Ethics & Research Science | | 2005 - Present | Member, Developmental Biology Graduate Group Steering Committee | | 2005 - Present | Lecturer, Department of Pathology & Immunology, Pathology Course | | 2005 - Present | Discussion Leader, Medical School Immunology Case Sessions | | 2005 - Present | Lecturer, Advanced Genetics, Bio 5491 | | 2005 - Present | Member, DBBS Admissions Committee | | 2004 - 2006 | Lecturer, Advanced Topics in Immunology 5272 | | | |
Diagnostic Expertise
| | Attend on autopsy service |
Clinical Interest
| | Anatomic and Molecular Pathology - Autopsy Pathology |
Selected Publications
| | Bredemeyer AJ, Geahlen JH, Weis VG, Huh WJ, Zinselmeyer BH, Srivatsan S, Miller MJ, Shaw AS, Mills JC. The gastric epithelial progenitor cell niche and differentiation of the zymogenic (chief) cell lineage. Dev Biol; 328:456-471, 2009 Abstract
| | Mysorekar IU, Isaacson-Schmid M, Walker JN, Mills JC, Hultgren, SJ. Bone Morphogenetic Protein 4 Signaling Regulates Epithelial Renewal in the Urinary Tract in Response to Uropathogenic Infection. Cell Host and Microbe;5:463-475, 2009 Abstract
| | Capoccia BJ, Huh WJ, Mills JC.. How form follows functional genomics: Gene expression profiling gastric epithelial cells with a particular discourse on the parietal cell. Physiological Genomics;37:67-78, 2009 Abstract
| | Cella M, Fuchs A, Vermi W, Facchetti F, Otero K, Lennerz JK, Doherty JM, Mills JC, Colonna M. A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity. Nature; 457:722-725, 2009 Abstract
| | Doherty JM, Geske MJ, Stappenbeck TS, Mills JC. Diverse adult stem cells share specific higher-order patterns of gene expression. Stem Cells; 26: 2124-30, 2008 Abstract
| | Calderon B, Suri A, Pan XO, Mills JC, Unanue ER. IFN-gamma-dependent regulatory circuits in immune inflammation highlighted in diabetes. J. Immunol.;181:6964-74, 2008 Abstract
| | 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.;134:211-222, 2007 Abstract
| | Lugus JJ, Chung YS, Mills JC, Kim SI, Grass JA, Kyba M, Doherty JM, Bresnick EH, Choi K. GATA2 functions at multiple steps in hemangioblast development and differentiation. Development;134(2):393-405, 2007 Abstract
| | Huh WJ, Pan XO, Mysorekar IU, Mills JC. Location, allocation, relocation: isolating adult tissue stem cells in three dimensions. Curr Opin Biotechnol;17:511-517, 2006 Abstract
| | Doherty JM, Carmichael LK, Mills JC. GOurmet: A tool for quantitative comparison and visualization of gene expression profiles based on gene ontology (GO) distributions. BMC Bioinformatics 7:151, 2006 Abstract
| | Giannakis M, Stappenbeck TS, *Mills JC (co first author), Leip DG, Lovett M, Clifton SW, Ippolito JE. 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
| | Syder AJ, Karam SM, Mills JC, Ippolito JE, Ansari HR, Farook V, Gordon JI. A transgenic mouse model of metastatic carcinoma involving transdifferentiation of a gastric epithelial lineage progenitor to a neuroendocrine phenotype. Proc Natl Acad Sci USA 101:4471-4476, 2004 Abstract
| | Mills JC, Andersson N, Stappenbeck TS, Chen CC, Gordon JI. Molecular characterization of mouse gastric zymogenic cells. J Biol Chem 278: 46138-46145, 2003 Abstract
| | 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 [This article featured in a Selected Summary by Erwin CR, Jarboe M, Warner BW in Gastroenterology 125:266-267 w, 2002 Abstract
| | Mills JC, Gordon JI. A new approach for filtering noise from high-density oligonucleotide microarray datasets. Nucleic Acids Res 29:E72, 2001 Abstract
| | Mills JC, Roth KA, Cagan RL, Gordon JI. DNA microarrays and beyond: completing the journey from tissue to cell. Nat Cell Biol 3:E175-178, 2001 Abstract
| | 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 Abstract
| | Mills JC, Gordon JI. The intestinal stem cell niche: There grows the neighborhood. Proc Natl Acad Sci USA 98:12334-12336, 2001 Abstract
| | Mills JC, Stone NL, Pittman RN. Extranuclear apoptosis: The role of the cytoplasm in the execution phase. J Cell Biol 146:703-708, 1999 Abstract
| | Liu JY, Seno H, Miletic AV, Mills JC, Swat W, Stappenbeck TS. Vav proteins are necessary for correct differentiation of mouse cecal and colonic enterocytes. J Cell Sci, 122:324-33 Abstract
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