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Edward E. Morrisey

Andrew James Paris, Yuhong Liu, Junjie Mei, Ning Dai, Lei Guo, Lynn Spruce, Kristin Hudock, Jacob Brenner, William Zacharias, Hankun Mei, April Slamowitz, Kartik Bhamidipati, Michael F Beers, Steven H Seeholzer, Edward E Morrisey, G Scott Worthen
Alveolar epithelial regeneration is essential for resolution of the acute respiratory distress syndrome (ARDS). Although neutrophils have traditionally been considered mediators of epithelial damage, recent studies suggest they promote type II pneumocyte (AT2) proliferation, which is essential for regenerating alveolar epithelium. These studies did not, however, evaluate this relationship in an in vivo model of alveolar epithelial repair following injury. To determine if neutrophils influence alveolar epithelial repair in vivo, we developed a unilateral acid injury model that creates a severe yet survivable injury with features similar to ARDS...
September 30, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Melinda Snitow, MinMin Lu, Lan Cheng, Su Zhou, Edward E Morrisey
During development, the lung mesoderm generates a variety of cell lineages including airway and vascular smooth muscle. Epigenetic changes in adult lung mesodermal lineages are thought to contribute towards diseases such as idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease, although which factors regulate early lung mesoderm development are unknown. We show that the Polycomb Repressive Complex 2 (PRC2) component Ezh2 is required to restrict smooth muscle differentiation in the developing lung mesothelium...
August 30, 2016: Development
Shanru Li, Michael Morley, MinMin Lu, Su Zhou, Kathleen Stewart, Catherine A French, Haley O Tucker, Simon E Fisher, Edward E Morrisey
The inhibitory mechanisms that prevent gene expression programs from one tissue to be expressed in another are poorly understood. Foxp1/2/4 are forkhead transcription factors that repress gene expression and are individually important for endoderm development. We show that combined loss of all three Foxp1/2/4 family members in the developing anterior foregut endoderm leads to a loss of lung endoderm lineage commitment and subsequent development. Foxp1/2/4 deficient lungs express high levels of transcriptional regulators not normally expressed in the developing lung, including Pax2, Pax8, Pax9 and the Hoxa9-13 cluster...
August 15, 2016: Developmental Biology
Ning Li, Maryam Yousefi, Angela Nakauka-Ddamba, John W Tobias, Shane T Jensen, Edward E Morrisey, Christopher J Lengner
BACKGROUND: Canonical Wnt pathway signaling is necessary for maintaining the proliferative capacity of mammalian intestinal crypt base columnar stem cells (CBCs). Furthermore, dysregulation of the Wnt pathway is a major contributor to disease, including oncogenic transformation of the intestinal epithelium. Given the critical importance of this pathway, numerous tools have been used as proxy measures for Wnt pathway activity, yet the relationship between Wnt target gene expression and reporter allele activity within individual cells at the crypt base remains unclear...
August 2016: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Xiaoru Wang, Yi Wang, Melinda E Snitow, Kathleen M Stewart, Shanru Li, MinMin Lu, Edward E Morrisey
The commitment and differentiation of the alveolar type I (AT1) cell lineage is a critical step for the formation of distal lung saccules, which are the primitive alveolar units required for postnatal respiration. How AT1 cells arise from the distal lung epithelial progenitor cells prior to birth and whether this process depends on a developmental niche instructed by mesenchymal cells is poorly understood. We show that mice lacking histone deacetylase 3 specifically in the developing lung mesenchyme display lung hypoplasia including decreased mesenchymal proliferation and a severe impairment of AT1 cell differentiation...
June 15, 2016: Developmental Biology
Shanru Li, Cynthia Koziol-White, Joseph Jude, Meiqi Jiang, Hengjiang Zhao, Gaoyuan Cao, Edwin Yoo, William Jester, Michael P Morley, Su Zhou, Yi Wang, Min Min Lu, Reynold A Panettieri, Edward E Morrisey
Asthma is one of the most common chronic diseases globally and can be divided into presenting with or without an immune response. Current therapies have little effect on nonimmune disease, and the mechanisms that drive this type of asthma are poorly understood. Here, we have shown that loss of the transcription factors forkhead box P1 (Foxp1) and Foxp4, which are critical for lung epithelial development, in the adult airway epithelium evokes a non-Th2 asthma phenotype that is characterized by airway hyperresponsiveness (AHR) without eosinophilic inflammation...
May 2, 2016: Journal of Clinical Investigation
Jeffrey A Whitsett, Edward E Morrisey
No abstract text is available yet for this article.
February 12, 2016: Science
Yi Wang, David B Frank, Michael P Morley, Su Zhou, Xiaoru Wang, Min Min Lu, Mitchell A Lazar, Edward E Morrisey
The terminal stages of pulmonary development, called sacculation and alveologenesis, involve both differentiation of distal lung endoderm progenitors and extensive cellular remodeling of the resultant epithelial lineages. These processes are coupled with dramatic expansion of distal airspace and surface area. Despite the importance of these late developmental processes and their relation to neonatal respiratory diseases, little is understood about the molecular and cellular pathways critical for their successful completion...
February 8, 2016: Developmental Cell
Rieko Ajima, Joseph A Bisson, Jay-Christian Helt, Masa-Aki Nakaya, Raymond Habas, Lino Tessarollo, Xi He, Edward E Morrisey, Terry P Yamaguchi, Ethan David Cohen
Wnt ligands regulate heart morphogenesis but the underlying mechanisms remain unclear. Two Formin-related proteins, DAAM1 and 2, were previously found to bind the Wnt effector Disheveled. Here, since DAAM1 and 2 nucleate actin and mediate Wnt-induced cytoskeletal changes, a floxed-allele of Daam1 was used to disrupt its function specifically in the myocardium and investigate Wnt-associated pathways. Homozygous Daam1 conditional knockout (CKO) mice were viable but had misshapen hearts and poor cardiac function...
December 1, 2015: Developmental Biology
Rebecca Windmueller, Edward E Morrisey
No abstract text is available yet for this article.
October 23, 2015: Circulation Research
Tien Peng, David B Frank, Rachel S Kadzik, Michael P Morley, Komal S Rathi, Tao Wang, Su Zhou, Lan Cheng, Min Min Lu, Edward E Morrisey
Postnatal tissue quiescence is thought to be a default state in the absence of a proliferative stimulus such as injury. Although previous studies have demonstrated that certain embryonic developmental programs are reactivated aberrantly in adult organs to drive repair and regeneration, it is not well understood how quiescence is maintained in organs such as the lung, which displays a remarkably low level of cellular turnover. Here we demonstrate that quiescence in the adult lung is an actively maintained state and is regulated by hedgehog signalling...
October 22, 2015: Nature
Daniel T Swarr, Edward E Morrisey
The respiratory endoderm develops from a small cluster of cells located on the ventral anterior foregut. This population of progenitors generates the myriad epithelial lineages required for proper lung function in adults through a complex and delicately balanced series of developmental events controlled by many critical signaling and transcription factor pathways. In the past decade, understanding of this process has grown enormously, helped in part by cell lineage fate analysis and deep sequencing of the transcriptomes of various progenitors and differentiated cell types...
2015: Annual Review of Cell and Developmental Biology
Wenli Yang, Ying Liu, Katherine J Slovik, Joseph C Wu, Stephen A Duncan, Daniel J Rader, Edward E Morrisey
Although significant advancement has been made in the induced pluripotent stem cell (iPSC) field, current methods for iPSC derivation are labor intensive and costly. These methods involve manual selection, expansion, and characterization of multiple clones for each reprogrammed cell sample and therefore significantly hampers the feasibility of studies where a large number of iPSCs need to be derived. To develop higher throughput iPSC reprogramming methods, we generated iPSCs as a pooled culture using rigorous cell surface pluripotent marker selection with TRA-1-60 or SSEA4 antibodies followed by Magnetic Activated Cell Sorting (MACS)...
2015: PloS One
Rajan Jain, Deqiang Li, Mudit Gupta, Lauren J Manderfield, Jamie L Ifkovits, Qiaohong Wang, Feiyan Liu, Ying Liu, Andrey Poleshko, Arun Padmanabhan, Jeffrey C Raum, Li Li, Edward E Morrisey, Min Min Lu, Kyoung-Jae Won, Jonathan A Epstein
Cardiac progenitor cells are multipotent and give rise to cardiac endothelium, smooth muscle, and cardiomyocytes. Here, we define and characterize the cardiomyoblast intermediate that is committed to the cardiomyocyte fate, and we characterize the niche signals that regulate commitment. Cardiomyoblasts express Hopx, which functions to coordinate local Bmp signals to inhibit the Wnt pathway, thus promoting cardiomyogenesis. Hopx integrates Bmp and Wnt signaling by physically interacting with activated Smads and repressing Wnt genes...
June 26, 2015: Science
Jason M Spaeth, Chad S Hunter, Lauren Bonatakis, Min Guo, Catherine A French, Ian Slack, Manami Hara, Simon E Fisher, Jorge Ferrer, Edward E Morrisey, Ben Z Stanger, Roland Stein
AIMS/HYPOTHESIS: Several forkhead box (FOX) transcription factor family members have important roles in controlling pancreatic cell fates and maintaining beta cell mass and function, including FOXA1, FOXA2 and FOXM1. In this study we have examined the importance of FOXP1, FOXP2 and FOXP4 of the FOXP subfamily in islet cell development and function. METHODS: Mice harbouring floxed alleles for Foxp1, Foxp2 and Foxp4 were crossed with pan-endocrine Pax6-Cre transgenic mice to generate single and compound Foxp mutant mice...
August 2015: Diabetologia
Hanrui Zhang, Chenyi Xue, Rhia Shah, Kate Bermingham, Christine C Hinkle, Wenjun Li, Amrith Rodrigues, Jennifer Tabita-Martinez, John S Millar, Marina Cuchel, Evanthia E Pashos, Ying Liu, Ruilan Yan, Wenli Yang, Sager J Gosai, Daniel VanDorn, Stella T Chou, Brian D Gregory, Edward E Morrisey, Mingyao Li, Daniel J Rader, Muredach P Reilly
RATIONALE: An efficient and reproducible source of genotype-specific human macrophages is essential for study of human macrophage biology and related diseases. OBJECTIVE: To perform integrated functional and transcriptome analyses of human induced pluripotent stem cell-derived macrophages (IPSDMs) and their isogenic human peripheral blood mononuclear cell-derived macrophage (HMDM) counterparts and assess the application of IPSDM in modeling macrophage polarization and Mendelian disease...
June 19, 2015: Circulation Research
Ying Tian, Ying Liu, Tao Wang, Ning Zhou, Jun Kong, Li Chen, Melinda Snitow, Michael Morley, Deqiang Li, Nataliya Petrenko, Su Zhou, Minmin Lu, Erhe Gao, Walter J Koch, Kathleen M Stewart, Edward E Morrisey
In contrast to lower vertebrates, the mammalian heart has limited capacity to regenerate after injury in part due to ineffective reactivation of cardiomyocyte proliferation. We show that the microRNA cluster miR302-367 is important for cardiomyocyte proliferation during development and is sufficient to induce cardiomyocyte proliferation in the adult and promote cardiac regeneration. In mice, loss of miR302-367 led to decreased cardiomyocyte proliferation during development. In contrast, increased miR302-367 expression led to a profound increase in cardiomyocyte proliferation, in part through repression of the Hippo signal transduction pathway...
March 18, 2015: Science Translational Medicine
Melinda E Snitow, Shanru Li, Michael P Morley, Komal Rathi, Min Min Lu, Rachel S Kadzik, Kathleen M Stewart, Edward E Morrisey
The development of the lung epithelium is regulated in a stepwise fashion to generate numerous differentiated and stem cell lineages in the adult lung. How these different lineages are generated in a spatially and temporally restricted fashion remains poorly understood, although epigenetic regulation probably plays an important role. We show that the Polycomb repressive complex 2 component Ezh2 is highly expressed in early lung development but is gradually downregulated by late gestation. Deletion of Ezh2 in early lung endoderm progenitors leads to the ectopic and premature appearance of Trp63+ basal cells that extend the entire length of the airway...
January 1, 2015: Development
Rachel S Kadzik, Ethan David Cohen, Michael P Morley, Kathleen M Stewart, Min Min Lu, Edward E Morrisey
Changing the morphology of a simple epithelial tube to form a highly ramified branching network requires changes in cell behavior that lead to tissue-wide changes in organ shape. How epithelial cells in branched organs modulate their shape and behavior to promote bending and sculpting of the epithelial sheet is not well understood, and the mechanisms underlying this process remain obscure. We show that the Wnt receptor Frizzled 2 (Fzd2) is required for domain branch formation during the initial establishment of the respiratory tree...
August 26, 2014: Proceedings of the National Academy of Sciences of the United States of America
Brigid L M Hogan, Christina E Barkauskas, Harold A Chapman, Jonathan A Epstein, Rajan Jain, Connie C W Hsia, Laura Niklason, Elizabeth Calle, Andrew Le, Scott H Randell, Jason Rock, Melinda Snitow, Matthew Krummel, Barry R Stripp, Thiennu Vu, Eric S White, Jeffrey A Whitsett, Edward E Morrisey
Respiratory disease is the third leading cause of death in the industrialized world. Consequently, the trachea, lungs, and cardiopulmonary vasculature have been the focus of extensive investigations. Recent studies have provided new information about the mechanisms driving lung development and differentiation. However, there is still much to learn about the ability of the adult respiratory system to undergo repair and to replace cells lost in response to injury and disease. This Review highlights the multiple stem/progenitor populations in different regions of the adult lung, the plasticity of their behavior in injury models, and molecular pathways that support homeostasis and repair...
August 7, 2014: Cell Stem Cell
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