Molecular & Cellular Biology Program firstname.lastname@example.org University of Iowa 357 Medical Research Center Iowa City, IA 52242-1182 Phone: 319-335-7748 Fax: 319-335-7656
Role of Wnt Signaling during Submucosal Gland Morphogenesis
Submucosal glands are epithelial tubule structures located in between the cartilage rings of the trachea and upper airways that have been identified as a progenitor cell niche. We believe that understanding the developmental processes that regulate the formation of these structures will give us insight into how the progenitor cells are maintained during normal homeostasis and in disease states of submucosal glands. One such example of a diseased state in submucosal glands is cystic fibrosis where submucosal glands are in hypertrophy. In this light, our lab has demonstrated that a transcription factor, Lymphoid enhancing factor-1 (Lef-1), is expressed during the initial stages of airway progenitor cell commitment to form submucosal glands and is required for glands to develop in the developing lung. In addition, several inhibitory and inductive factors have been identified to be involved in regulating Lef-1 transcriptional activity through its promoter. Our lab has also shown that the canonical Wnt signaling pathway can mediate Lef-1 expression. My research focuses on the function of candidate transcription factors that may regulate Lef-1 gene expression during submucosal gland development and the molecular mechanisms responsible for maintaining stem cell niche function in airway glands. I am currently developing transgenic mouse models, knockout mouse models, as well as transcriptional assays to study the regulation of Lef-1 expression during airway submucosal gland morphogenesis.
Olivier AK, Yi Y, Sun X, Sui H, Liang B, Hu S, Xie W, Fisher JT, Keiser NW,
Lei D, Zhou W, Yan Z, Li G, Evans TI, Meyerholz DK, Wang K, Stewart ZA, Norris AW, Engelhardt JF. Abnormal endocrine pancreas function at birth in cystic fibrosis ferrets. J Clin Invest. 2012 Sep 17. pii: 60610. doi: 10.1172/JCI60610. [Epub ahead of print] PubMed PMID: 22996690.
Shelton DN, Fornalik H, Neff T, Park SY, Bender D, DeGeest K, Liu X, Xie W, Meyerholz DK, Engelhardt JF, Goodheart MJ. The role of LEF1 in endometrial gland formation and carcinogenesis. PLoS One. 2012;7(7):e40312. Epub 2012 Jul 6. PubMed PMID: 22792274; PubMed Central PMCID: PMC3391280.
Xie W, Fisher JT, Lynch TJ, Luo M, Evans TI, Neff TL, Zhou W, Zhang Y, Ou Y, Bunnett NW, Russo AF, Goodheart MJ, Parekh KR, Liu X, Engelhardt JF. CGRP induction in cystic fibrosis airways alters the submucosal gland progenitor cell niche in mice. J Clin Invest. 2011 Aug;121(8):3144-58. doi: 10.1172/JCI41857. Epub 2011 Jul 18. PubMed PMID: 21765217; PubMed Central PMCID: PMC3148720.
Liu X, Luo M, Xie W, Wells JM, Goodheart MJ, Engelhardt JF. Sox17 modulates Wnt3A/beta-catenin-mediated transcriptional activation of the Lef-1 promoter. Am J Physiol Lung Cell Mol Physiol. 2010 Nov;299(5):L694-710. Epub 2010 Aug 27. PubMed PMID: 20802155; PubMed Central PMCID: PMC2980392.
Copyright © 2008-2009 The University of Iowa