Beiyun Zhou, PhD

Associate Professor of Medicine

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Overview

Dr. Zhou’s research focuses on the delineation of mechanisms regulating alveolar epithelial cell (AEC) function, differentiation and plasticity in the context of lung injury and repair. A major focus has been to elucidate pathways (e.g., Hippo/YAP, Wnt/B-catenin, TGF-B/Smad, Forkhead box (Fox) and GATA6) as well as transcriptomic and epigenomic regulations that control differentiation of the alveolar epithelium (including pulmonary stem/progenitor cell proliferation/differentiation) in order to understand how they are altered in disease and injury. Her current studies engaged in to investigate the role of endoplasmic reticulum (ER) stress and the ER master regulator GRP78 in AEC abnormalities in chronic lung diseases such as idiopathic pulmonary fibrosis (IPF) using AEC-specific Grp78 knockout mice model. Her goal is to examine signaling pathways that modulate aberrant epithelial-mesenchymal interactions underlying ER stress-mediated fibrosis and identify new therapeutic approaches for pulmonary fibrosis.

Publications

  • Sorafenib inhibits invasion of multicellular organoids that mimic Lymphangioleiomyomatosis nodules bioRxiv. 2023 Jun 12. . View in PubMed
  • Alveolar type I cells can give rise to KRAS-induced lung adenocarcinoma Cell Rep. 2023 12 26; 42(12):113286. . View in PubMed
  • Development of human alveolar epithelial cell models to study distal lung biology and disease iScience. 2022 Feb 18; 25(2):103780. . View in PubMed
  • Wnt5a Promotes AT1 and Represses AT2 Lineage-Specific Gene Expression in a Cell-Context-Dependent Manner Stem Cells. 2022 07 27; 40(7):691-703. . View in PubMed
  • FOXO1 Couples KGF and PI-3K/AKT Signaling to NKX21-Regulated Differentiation of Alveolar Epithelial Cells. Cells. 2022 03 26; 11(7). . View in PubMed
  • Endoplasmic reticulum chaperone GRP78/BiP is critical for mutant Kras-driven lung tumorigenesis Oncogene. 2021 05; 40(20):3624-3632. . View in PubMed
  • Fibrinolytic niche is required for alveolar type 2 cell-mediated alveologenesis via a uPA-A6-CD44+-ENaC signal cascade Signal Transduct Target Ther. 2021 02 27; 6(1):97. . View in PubMed
  • TENET 20: Identification of key transcriptional regulators and enhancers in lung adenocarcinoma. PLoS Genet. 2020 09; 16(9):e1009023. . View in PubMed
  • WNT5a-ROR Signaling Is Essential for Alveologenesis Cells. 2020 02 07; 9(2). . View in PubMed
  • Genome-wide integration of microRNA and transcriptomic profiles of differentiating human alveolar epithelial cells Am J Physiol Lung Cell Mol Physiol. 2020 07 01; 319(1):L173-L184. . View in PubMed
  • Integrated Single-Cell RNA-Sequencing Analysis of Aquaporin 5-Expressing Mouse Lung Epithelial Cells Identifies GPRC5A as a Novel Validated Type I Cell Surface Marker Cells. 2020 11 11; 9(11). . View in PubMed
  • Grp78 Loss in Epithelial Progenitors Reveals an Age-linked Role for Endoplasmic Reticulum Stress in Pulmonary Fibrosis Am J Respir Crit Care Med. 2020 01 15; 201(2):198-211. . View in PubMed
  • LINC00261 Is an Epigenetically Regulated Tumor Suppressor Essential for Activation of the DNA Damage Response Cancer Res. 2019 Jun 15; 79(12):3050-3062. . View in PubMed
  • Positional integration of lung adenocarcinoma susceptibility loci with primary human alveolar epithelial cell epigenomes Epigenomics. 2018 09; 10(9):1167-1187. . View in PubMed
  • Claudin-18-mediated YAP activity regulates lung stem and progenitor cell homeostasis and tumorigenesis J Clin Invest. 2018 03 01; 128(3):970-984. . View in PubMed
  • CLDN181 attenuates malignancy and related signaling pathways of lung adenocarcinoma in vivo and in vitro. Int J Cancer. 2018 12 15; 143(12):3169-3180. . View in PubMed
  • Cell-specific expression of aquaporin-5 (Aqp5) in alveolar epithelium is directed by GATA6/Sp1 via histone acetylation Sci Rep. 2017 06 14; 7(1):3473. . View in PubMed
  • Region-specific role for Pten in maintenance of epithelial phenotype and integrity Am J Physiol Lung Cell Mol Physiol. 2017 01 01; 312(1):L131-L142. . View in PubMed
  • p300/ß-Catenin Interactions Regulate Adult Progenitor Cell Differentiation Downstream of WNT5a/Protein Kinase C (PKC) J Biol Chem. 2016 Mar 18; 291(12):6569-82. . View in PubMed
  • Combinations of differentiation markers distinguish subpopulations of alveolar epithelial cells in adult lung Am J Physiol Lung Cell Mol Physiol. 2016 Jan 15; 310(2):L114-20. . View in PubMed
  • Pleiotropic Analysis of Lung Cancer and Blood Triglycerides J Natl Cancer Inst. 2016 12; 108(12). . View in PubMed
  • The 78-kD Glucose-Regulated Protein Regulates Endoplasmic Reticulum Homeostasis and Distal Epithelial Cell Survival during Lung Development Am J Respir Cell Mol Biol. 2016 07; 55(1):135-49. . View in PubMed
  • The importance of detailed epigenomic profiling of different cell types within organs Epigenomics. 2016 06; 8(6):817-29. . View in PubMed
  • Transforming Growth Factor-ß1 Induced Epithelial Mesenchymal Transition is blocked by a chemical antagonist of translation factor eIF4E Sci Rep. 2015 Dec 18; 5:18233. . View in PubMed
  • Transcriptomic Profiling of Primary Alveolar Epithelial Cell Differentiation in Human and Rat Genom Data. 2014 Dec 01; 2:105-109. . View in PubMed
  • TRIM72 is required for effective repair of alveolar epithelial cell wounding Am J Physiol Lung Cell Mol Physiol. 2014 Sep 15; 307(6):L449-59. . View in PubMed
  • Knockout mice reveal key roles for claudin 18 in alveolar barrier properties and fluid homeostasis Am J Respir Cell Mol Biol. 2014 Aug; 51(2):210-22. . View in PubMed
  • Characterizing the genetic basis of methylome diversity in histologically normal human lung tissue Nat Commun. 2014 Feb 27; 5:3365. . View in PubMed
  • Integrated transcriptomic and epigenomic analysis of primary human lung epithelial cell differentiation PLoS Genet. 2013 Jun; 9(6):e1003513. . View in PubMed
  • Aqp5 is a new transcriptional target of Dot1a and a regulator of Aqp2 PLoS One. 2013; 8(1):e53342. . View in PubMed
  • GRP78/BiP is a novel downstream target of IGF-1 receptor mediated signaling J Cell Physiol. 2012 Dec; 227(12):3803-11. . View in PubMed
  • Interactions between ß-catenin and transforming growth factor-ß signaling pathways mediate epithelial-mesenchymal transition and are dependent on the transcriptional co-activator cAMP-response element-binding protein (CREB)-binding protein (CBP) J Biol Chem. 2012 Mar 02; 287(10):7026-38. . View in PubMed
  • Ligand-independent transforming growth factor-ß type I receptor signalling mediates type I collagen-induced epithelial-mesenchymal transition J Pathol. 2012 Mar; 226(4):633-44. . View in PubMed
  • Troglitazone attenuates TGF-ß1-induced EMT in alveolar epithelial cells via a PPAR? -independent mechanism. PLoS One. 2012; 7(6):e38827.. View in PubMed
  • Role of endoplasmic reticulum stress in epithelial-mesenchymal transition of alveolar epithelial cells: effects of misfolded surfactant protein Am J Respir Cell Mol Biol. 2011 Sep; 45(3):498-509. . View in PubMed
  • Epithelium-specific deletion of TGF-ß receptor type II protects mice from bleomycin-induced pulmonary fibrosis J Clin Invest. 2011 Jan; 121(1):277-87. . View in PubMed
  • Inhibition of Wnt/beta-catenin/CREB binding protein (CBP) signaling reverses pulmonary fibrosis Proc Natl Acad Sci U S A. 2010 Aug 10; 107(32):14309-14. . View in PubMed
  • Directed expression of Cre in alveolar epithelial type 1 cells Am J Respir Cell Mol Biol. 2010 Aug; 43(2):173-8. . View in PubMed
  • Rat aquaporin-5 43-kb 5′-flanking region differentially regulates expression in salivary gland and lung in vivo. Am J Physiol Cell Physiol. 2008 Jul; 295(1):C111-20. . View in PubMed
  • Foxp2 inhibits Nkx21-mediated transcription of SP-C via interactions with the Nkx2. 1 homeodomain. Am J Respir Cell Mol Biol. 2008 Jun; 38(6):750-8. . View in PubMed
  • Conserved elements within first intron of aquaporin-5 (Aqp5) function as transcriptional enhancers Biochem Biophys Res Commun. 2007 Apr 27; 356(1):26-31. . View in PubMed
  • Hypertonic induction of aquaporin-5: novel role of hypoxia-inducible factor-1alpha Am J Physiol Cell Physiol. 2007 Apr; 292(4):C1280-90. . View in PubMed
  • Transcriptional regulation by targeted expression of architectural transcription factor high mobility group A2 in salivary glands of transgenic mice Eur J Oral Sci. 2007 Feb; 115(1):30-9. . View in PubMed
  • Alveolar epithelial type I cells express beta2-adrenergic receptors and G-protein receptor kinase 2 J Histochem Cytochem. 2004 Jun; 52(6):759-67. . View in PubMed
  • Subunit-specific coordinate upregulation of sodium pump activity in alveolar epithelial cells by lentivirus-mediated gene transfer Hum Gene Ther. 2004 May; 15(5):457-68. . View in PubMed
  • Identification of three genes of known function expressed by alveolar epithelial type I cells Am J Respir Cell Mol Biol. 2003 Jul; 29(1):98-105. . View in PubMed
  • Na transport proteins are expressed by rat alveolar epithelial type I cells Am J Physiol Lung Cell Mol Physiol. 2002 Apr; 282(4):L599-608. . View in PubMed
  • Effects of transdifferentiation and EGF on claudin isoform expression in alveolar epithelial cells J Appl Physiol (1985). 2005 Jan; 98(1):322-8. . View in PubMed