Jason Mills, MD, PhD
Associate Professor of Medicine
Developmental Biology and of Pathology & Immunology
My lab is using a multipronged approach to understand the cellular and molecular details of adult stem cell biology in the mouse and human GI tract. We are interested both in normal developmental pathways from the multipotent stem cell and in uncovering the aberrations that occur when those pathways go awry (e.g., in stomach cancer). In particular, we have focused recently on how mucus-secreting neck cells arise from a multipotent gastric epithelial stem cell and then undergo a dramatic differentiation into digestive-enzyme-secreting zymogenic (chief) cells. In one set of experiments, we combine 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 (BHLHA15), required for normal maturation of zymogenic cells. We have shown that differentiation of zymogenic cells occurs because another transcription factor, XBP1, controls expression of genes that induce massive deposition of rough endoplasmic reticulum (rER) and also upregulates MIST1, which, in turn, regulates genes that form the cell’s apical storehouse of large secretory granules. In the absence of XBP1, neither rER nor vesicles form normally, and zymogenic cells show metaplastic differentiation: namely, they are unable to stop expression of neck (i.e., progenitor) genes.
Jason Mills joined the Division of Gastroenterology, Department of Medicine in January, 2011. He also holds appointments in Pathology & Immunology as well as Developmental Biology. Dr. Mills graduated summa cum laude from Washington University as an undergraduate, where he was the Moog scholar in humanities and sciences, majoring in Russian and biology. He received his MD and PhD from the University of Pennsylvania, where he studied the role of the cytoskeleton in apoptosis. He came back to Washington University for his residency in Anatomical Pathology and a postdoctoral fellowship in Jeff Gordon’s lab, where he studied genomics of gastric epithelial differentiation. He has had his own lab at Washington University since 2004, studying epithelial differentiation in the GI tract during development, injury/inflammation, and carcinogenesis. Dr. Mills is the recipient of an American Cancer Society Research Scholar Award, as well as the 2010 Funderburg Award in Gastric Biology Related to Cancer and the 2010 and 2014 Washington University Outstanding Graduate Student Faculty Mentor Award. He is an Associate Editor for the journal Physiological Genomics, and he serves on the Editorial Board of Gastroenterology, Digestive Diseases and Sciences, Cellular and Molecular Gastroenterology and Hepatology, and The American Journal of Physiology GI Liver. Dr. Mills has over 70 articles and books, which have been cited over 3300 times with an h index of 27.