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Edward E. Morrisey

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https://www.readbyqxmd.com/read/28589954/wnt10a-mutation-causes-ectodermal-dysplasia-by-impairing-progenitor-cell-proliferation-and-klf4-mediated-differentiation
#1
Mingang Xu, Jeremy Horrell, Melinda Snitow, Jiawei Cui, Heather Gochnauer, Camille M Syrett, Staci Kallish, John T Seykora, Fei Liu, Dany Gaillard, Jonathan P Katz, Klaus H Kaestner, Brooke Levin, Corinne Mansfield, Jennifer E Douglas, Beverly J Cowart, Michael Tordoff, Fang Liu, Xuming Zhu, Linda A Barlow, Adam I Rubin, John A McGrath, Edward E Morrisey, Emily Y Chu, Sarah E Millar
Human WNT10A mutations are associated with developmental tooth abnormalities and adolescent onset of a broad range of ectodermal defects. Here we show that β-catenin pathway activity and adult epithelial progenitor proliferation are reduced in the absence of WNT10A, and identify Wnt-active self-renewing stem cells in affected tissues including hair follicles, sebaceous glands, taste buds, nails and sweat ducts. Human and mouse WNT10A mutant palmoplantar and tongue epithelia also display specific differentiation defects that are mimicked by loss of the transcription factor KLF4...
June 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28546511/the-nanci-nkx2-1-gene-duplex-buffers-nkx2-1-expression-to-maintain-lung-development-and-homeostasis
#2
Michael J Herriges, David J Tischfield, Zheng Cui, Michael P Morley, Yumiao Han, Apoorva Babu, Su Li, MinMin Lu, Isis Cendan, Benjamin A Garcia, Stewart A Anderson, Edward E Morrisey
A subset of long noncoding RNAs (lncRNAs) is spatially correlated with transcription factors (TFs) across the genome, but how these lncRNA-TF gene duplexes regulate tissue development and homeostasis is unclear. We identified a feedback loop within the NANCI (Nkx2.1-associated noncoding intergenic RNA)-Nkx2.1 gene duplex that is essential for buffering Nkx2.1 expression, lung epithelial cell identity, and tissue homeostasis. Within this locus, Nkx2.1 directly inhibits NANCI, while NANCI acts in cis to promote Nkx2...
May 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28514664/lack-of-mttp-activity-in-pluripotent-stem-cell-derived-hepatocytes-and-cardiomyocytes-abolishes-apob-secretion-and-increases-cell-stress
#3
Ying Liu, Donna M Conlon, Xin Bi, Katherine J Slovik, Jianting Shi, Hailey I Edelstein, John S Millar, Ali Javaheri, Marina Cuchel, Evanthia E Pashos, Jahangir Iqbal, M Mahmood Hussain, Robert A Hegele, Wenli Yang, Stephen A Duncan, Daniel J Rader, Edward E Morrisey
Abetalipoproteinemia (ABL) is an inherited disorder of lipoprotein metabolism resulting from mutations in microsomal triglyceride transfer protein (MTTP). In addition to expression in the liver and intestine, MTTP is expressed in cardiomyocytes, and cardiomyopathy has been reported in several ABL cases. Using induced pluripotent stem cells (iPSCs) generated from an ABL patient homozygous for a missense mutation (MTTP(R46G)), we show that human hepatocytes and cardiomyocytes exhibit defects associated with ABL disease, including loss of apolipoprotein B (apoB) secretion and intracellular accumulation of lipids...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28388432/large-diverse-population-cohorts-of-hipscs-and-derived-hepatocyte-like-cells-reveal-functional-genetic-variation-at-blood-lipid-associated-loci
#4
Evanthia E Pashos, YoSon Park, Xiao Wang, Avanthi Raghavan, Wenli Yang, Deepti Abbey, Derek T Peters, Juan Arbelaez, Mayda Hernandez, Nicolas Kuperwasser, Wenjun Li, Zhaorui Lian, Ying Liu, Wenjian Lv, Stacey L Lytle-Gabbin, Dawn H Marchadier, Peter Rogov, Jianting Shi, Katherine J Slovik, Ioannis M Stylianou, Li Wang, Ruilan Yan, Xiaolan Zhang, Sekar Kathiresan, Stephen A Duncan, Tarjei S Mikkelsen, Edward E Morrisey, Daniel J Rader, Christopher D Brown, Kiran Musunuru
Genome-wide association studies have struggled to identify functional genes and variants underlying complex phenotypes. We recruited a multi-ethnic cohort of healthy volunteers (n = 91) and used their tissue to generate induced pluripotent stem cells (iPSCs) and hepatocyte-like cells (HLCs) for genome-wide mapping of expression quantitative trait loci (eQTLs) and allele-specific expression (ASE). We identified many eQTL genes (eGenes) not observed in the comparably sized Genotype-Tissue Expression project's human liver cohort (n = 96)...
April 6, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28388428/a-drug-screen-using-human-ipsc-derived-hepatocyte-like-cells-reveals-cardiac-glycosides-as-a-potential-treatment-for-hypercholesterolemia
#5
Max A Cayo, Sunil K Mallanna, Francesca Di Furio, Ran Jing, Lauren B Tolliver, Matthew Bures, Amanda Urick, Fallon K Noto, Evanthia E Pashos, Matthew D Greseth, Maciej Czarnecki, Paula Traktman, Wenli Yang, Edward E Morrisey, Markus Grompe, Daniel J Rader, Stephen A Duncan
Efforts to identify pharmaceuticals to treat heritable metabolic liver diseases have been hampered by the lack of models. However, cells with hepatocyte characteristics can be produced from induced pluripotent stem cells (iPSCs). Here, we have used hepatocyte-like cells generated from homozygous familial hypercholesterolemia (hoFH) iPSCs to identify drugs that can potentially be repurposed to lower serum LDL-C. We found that cardiac glycosides reduce the production of apolipoprotein B (apoB) from human hepatocytes in culture and the serum of avatar mice harboring humanized livers...
April 6, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28330813/atp-binding-cassette-transporter-a1-deficiency-in-human-induced-pluripotent-stem-cell-derived-hepatocytes-abrogates-hdl-biogenesis-and-enhances-triglyceride-secretion
#6
Xin Bi, Evanthia E Pashos, Marina Cuchel, Nicholas N Lyssenko, Mayda Hernandez, Antonino Picataggi, James McParland, Wenli Yang, Ying Liu, Ruilan Yan, Christopher Yu, Stephanie L DerOhannessian, Michael C Phillips, Edward E Morrisey, Stephen A Duncan, Daniel J Rader
Despite the recognized role of the ATP-binding Cassette Transporter A1 (ABCA1) in high-density lipoprotein (HDL) metabolism, our understanding of ABCA1 deficiency in human hepatocytes is limited. To define the functional effects of human hepatocyte ABCA1 deficiency, we generated induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells (HLCs) from Tangier disease (TD) and matched control subjects. Control HLCs exhibited robust cholesterol efflux to apolipoprotein A-I (apoA-I) and formed nascent HDL particles...
April 2017: EBioMedicine
https://www.readbyqxmd.com/read/27957616/developmental-pathways-in-lung-regeneration
#7
REVIEW
Collin T Stabler, Edward E Morrisey
The key processes of lung development have been elucidated in the past several decades, helping to identify and characterize the resident progenitor cells that ultimately generate the mature organ. The adult lung is a complex organ consisting in scores of different cell lineages that are remarkably quiescent in the absence of injury. Despite low cellular turnover, the lung can respond quickly and dramatically to acute damage, with spatially restricted stem and progenitor cells re-entering the cell cycle and differentiating to promote repair...
March 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/27880906/emergence-of-a-wave-of-wnt-signaling-that-regulates-lung-alveologenesis-by-controlling-epithelial-self-renewal-and-differentiation
#8
David B Frank, Tien Peng, Jarod A Zepp, Melinda Snitow, Tiffaney L Vincent, Ian J Penkala, Zheng Cui, Michael J Herriges, Michael P Morley, Su Zhou, Min Min Lu, Edward E Morrisey
Alveologenesis is the culmination of lung development and involves the correct temporal and spatial signals to generate the delicate gas exchange interface required for respiration. Using a Wnt-signaling reporter system, we demonstrate the emergence of a Wnt-responsive alveolar epithelial cell sublineage, which arises during alveologenesis, called the axin2+ alveolar type 2 cell, or AT2(Axin2). The number of AT2(Axin2) cells increases substantially during late lung development, correlating with a wave of Wnt signaling during alveologenesis...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27780343/gene-editing-and-genetic-lung-disease-basic-research-meets-therapeutic-application
#9
REVIEW
Deepthi Alapati, Edward E Morrisey
Although our understanding of the genetics and pathology of congenital lung diseases such as surfactant protein deficiency, cystic fibrosis, and alpha-1 antitrypsin deficiency is extensive, treatment options are lacking. Because the lung is a barrier organ in direct communication with the external environment, targeted delivery of gene corrective technologies to the respiratory system via intratracheal or intranasal routes is an attractive option for therapy. CRISPR/Cas9 gene-editing technology is a promising approach to repairing or inactivating disease-causing mutations...
March 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27694472/neutrophils-promote-alveolar-epithelial-regeneration-by-enhancing-type-ii-pneumocyte-proliferation-in-a-model-of-acid-induced-acute-lung-injury
#10
Andrew J Paris, Yuhong Liu, Junjie Mei, Ning Dai, Lei Guo, Lynn A Spruce, Kristin M Hudock, Jacob S Brenner, William J Zacharias, Hankun D Mei, April R 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 whether 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...
December 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27578795/ezh2-restricts-the-smooth-muscle-lineage-during-mouse-lung-mesothelial-development
#11
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 the factors that regulate early lung mesoderm development are unknown. We show in mouse that the PRC2 component Ezh2 is required to restrict smooth muscle differentiation in the developing lung mesothelium...
October 15, 2016: Development
https://www.readbyqxmd.com/read/27341756/foxp-transcription-factors-suppress-a-non-pulmonary-gene-expression-program-to-permit-proper-lung-development
#12
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
https://www.readbyqxmd.com/read/27264700/heterogeneity-in-readouts-of-canonical-wnt-pathway-activity-within-intestinal-crypts
#13
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
https://www.readbyqxmd.com/read/27141870/expression-of-histone-deacetylase-3-instructs-alveolar-type-i-cell-differentiation-by-regulating-a-wnt-signaling-niche-in-the-lung
#14
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
https://www.readbyqxmd.com/read/27088802/epithelium-generated-neuropeptide-y-induces-smooth-muscle-contraction-to-promote-airway-hyperresponsiveness
#15
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
https://www.readbyqxmd.com/read/26912844/inflammation-modulating-pulmonary-inflammation
#16
COMMENT
Jeffrey A Whitsett, Edward E Morrisey
No abstract text is available yet for this article.
February 12, 2016: Science
https://www.readbyqxmd.com/read/26832331/hdac3-dependent-epigenetic-pathway-controls-lung-alveolar-epithelial-cell-remodeling-and-spreading-via-mir-17-92-and-tgf-%C3%AE-signaling-regulation
#17
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
https://www.readbyqxmd.com/read/26526197/daam1-and-daam2-are-co-required-for-myocardial-maturation-and-sarcomere-assembly
#18
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
https://www.readbyqxmd.com/read/26494924/hippo-and-cardiac-hypertrophy-a-complex-interaction
#19
EDITORIAL
Rebecca Windmueller, Edward E Morrisey
No abstract text is available yet for this article.
October 23, 2015: Circulation Research
https://www.readbyqxmd.com/read/26436454/hedgehog-actively-maintains-adult-lung-quiescence-and-regulates-repair-and-regeneration
#20
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
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