Edward David Crandall, PhD, MD

Professor of Pathology

Hasting Foundation Professorship in Medicine

Director of the Will Rogers Institute Pulmonary Research Center

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Overview

Dr. Crandall’s research has been focused on the following topics: markers of alveolar epithelial cell development and differentiation, regulation of pulmonary epithelial cell differentiation, acute and chronic lung injury and the factors that influence recovery, transport properties of pulmonary alveolar epithelium, and biology of nanoparticle interactions with alveolar epithelial cells.

Dr. Crandall received his B.Ch.E. from Cooper Union, his M.S. and Ph.D. in chemical engineering from Northwestern University, and his M.D. from the University of Pennsylvania. His training in internal medicine and pulmonary/critical care medicine was undertaken at the Hospital of the University of Pennsylvania.

Awards

  • 2005
     -: Best Doctors of America, 2005
     –
  • National Institutes of Health: MERIT Award, 1987
     – 1997
  • National Institutes of Health: Research Career Development Award, 1975
     – 1980
  • Chair of Department of Medicine Scholarship, University of Pennsylvania
  • Special Fellowship, U.S. Public Health Service
  • Graduate Fellowship, National Science Foundation
  • Regents Scholarship, New York State

Research Funding

  • MAPGen Knowledge Base (MAPGenKB) and Coordination Center
    NIH · U01HL108634 · Aug 25, 2011 – May 31, 2018 · Role: Co-Principal Investigator
  • Interactions of engineered nanomaterials with lung alveolar epithelium
    NIH · RC2ES018782 · Sep 25, 2009 – Jun 30, 2012 · Role: Principal Investigator
  • Nanoparticle properties and alveolar epithelial barrier/transport functions
    NIH · R01ES017034 · Jun 15, 2009 – Mar 31, 2015 · Role: Principal Investigator
  • Absorption mechanisms for peptide/protein drugs via lung
    NIH · R01HL064365 · Sep 30, 1999 – Jul 31, 2010 · Role: Principal Investigator
  • AT1 vs AT2 cells: differential roles in alveolar function and biology
    NIH · R01HL038621 · Sep 1, 1986 – Jun 30, 2012 · Role: Principal Investigator
  • GATA-6: Key Regulator of AEC Transdifferentiation
    NIH · R01HL038578 · Sep 1, 1986 – Nov 30, 2008 · Role: Co-Principal Investigator
  • LUNG EPITHELIAL TRANSPORT PROPERTIES AND ALVEOLAR EDEMA
    NIH · R37HL038578 · Sep 1, 1986 – Aug 31, 1997 · Role: Principal Investigator
  • DETERMINANTS OF LUNG AND TISSUE CO2 EXCHANGE AND TRANSPO
    NIH · R01HL025669 · Aug 1, 1980 – Aug 31, 1986 · Role: Principal Investigator
  • LUNG EPITHELIAL TRANSPORT PROPERTIES AND ALVEOLAR EDEMA
    NIH · R01HL026223 · Aug 1, 1980 – Aug 31, 1986 · Role: Principal Investigator

Publications

  • Increased lung cell susceptibility to injury due to autophagic overload after exposure to nanoparticles. Am J Physiol Lung Cell Mol Physiol. 2026 Aug 01; 331(2):L197-L205.. View in PubMed
  • Claudin 4 Deletion Improves Gut Permeability and Survival in a Murine Model of Abdominal Sepsis. Shock. 2026 Apr 01; 65(4):710-726.. View in PubMed
  • In-house Fabrication of Nanoplastics of Tunable Composition and Application: Assessment of Bioelectric Changes in Primary Rat Lung Alveolar Epithelial Cell Monolayers Exposed to Nanoplastics. Bio Protoc. 2025 Jun 05; 15(11):e5329.. View in PubMed
  • Real-Time Autophagic Flux Measurements in Live Cells Using a Novel Fluorescent Marker DAPRed. Bio Protoc. 2024 Mar 05; 14(5):e4949.. View in PubMed
  • Kinetics of autophagic activity in nanoparticle-exposed lung adenocarcinoma (A549) cells. Autophagy Rep. 2023; 2(1).. View in PubMed
  • Characteristics of Passive Solute Transport across Primary Rat Alveolar Epithelial Cell Monolayers. Membranes (Basel). 2021 Apr 30; 11(5).. View in PubMed
  • Biokinetic modeling of nanoparticle interactions with lung alveolar epithelial cells: uptake, intracellular processing, and egress. Am J Physiol Regul Integr Comp Physiol. 2021 01 01; 320(1):R36-R43.. View in PubMed
  • Epithelial Vegfa Specifies a Distinct Endothelial Population in the Mouse Lung. Dev Cell. 2020 03 09; 52(5):617-630.e6.. View in PubMed
  • Evidence for Nanoparticle-Induced Lysosomal Dysfunction in Lung Adenocarcinoma (A549) Cells. Int J Mol Sci. 2019 Oct 23; 20(21).. View in PubMed
  • Transcriptional control of lung alveolar type 1 cell development and maintenance by NK homeobox 2-1. Proc Natl Acad Sci U S A. 2019 10 08; 116(41):20545-20555.. View in PubMed
  • CLDN18.1 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
  • Alveolar epithelial cell processing of nanoparticles activates autophagy and lysosomal exocytosis. Am J Physiol Lung Cell Mol Physiol. 2018 08 01; 315(2):L286-L300.. 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
  • Platelet CLEC-2 protects against lung injury via effects of its ligand podoplanin on inflammatory alveolar macrophages in the mouse. Am J Physiol Lung Cell Mol Physiol. 2017 Dec 01; 313(6):L1016-L1029.. View in PubMed
  • Oligopeptide Transport in Rat Lung Alveolar Epithelial Cells is Mediated by Pept2. Pharm Res. 2017 Dec; 34(12):2488-2497.. View in PubMed
  • Astrocytic tight junctions control inflammatory CNS lesion pathogenesis. J Clin Invest. 2017 Aug 01; 127(8):3136-3151.. 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
  • Cross-Species Transcriptome Profiling Identifies New Alveolar Epithelial Type I Cell-Specific Genes. Am J Respir Cell Mol Biol. 2017 03; 56(3):310-321.. 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
  • IL-1R1-MyD88 axis elicits papain-induced lung inflammation. Eur J Immunol. 2016 11; 46(11):2531-2541.. View in PubMed
  • Knockout Mice Reveal a Major Role for Alveolar Epithelial Type I Cells in Alveolar Fluid Clearance. Am J Respir Cell Mol Biol. 2016 09; 55(3):395-406.. View in PubMed
  • p300/β-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
  • A fluid secretion pathway unmasked by acinar-specific Tmem16A gene ablation in the adult mouse salivary gland. Proc Natl Acad Sci U S A. 2015 Feb 17; 112(7):2263-8.. View in PubMed
  • Claudin 4 knockout mice: normal physiological phenotype with increased susceptibility to lung injury. Am J Physiol Lung Cell Mol Physiol. 2014 Oct 01; 307(7):L524-36.. 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
  • DiseaseConnect: a comprehensive web server for mechanism-based disease-disease connections. Nucleic Acids Res. 2014 Jul; 42(Web Server issue):W137-46.. View in PubMed
  • Polystyrene nanoparticle exposure induces ion-selective pores in lipid bilayers. Biochim Biophys Acta. 2013 Sep; 1828(9):2215-22.. View in PubMed
  • Interlaboratory evaluation of in vitro cytotoxicity and inflammatory responses to engineered nanomaterials: the NIEHS Nano GO Consortium. Environ Health Perspect. 2013 Jun; 121(6):683-90.. View in PubMed
  • Nanoparticle translocation across mouse alveolar epithelial cell monolayers: species-specific mechanisms. Nanomedicine. 2013 Aug; 9(6):786-94.. View in PubMed
  • Troglitazone attenuates TGF-β1-induced EMT in alveolar epithelial cells via a PPARγ-independent mechanism. PLoS One. 2012; 7(6):e38827.. View in PubMed
  • Interactions between β-catenin and transforming growth factor-β 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-β type I receptor signalling mediates type I collagen-induced epithelial-mesenchymal transition. J Pathol. 2012 Mar; 226(4):633-44.. View in PubMed
  • Translocation of PEGylated quantum dots across rat alveolar epithelial cell monolayers. Int J Nanomedicine. 2011; 6:2849-57.. View in PubMed
  • Nanomaterial interactions with and trafficking across the lung alveolar epithelial barrier: implications for health effects of air-pollution particles. Air Qual Atmos Health. 2011 Mar 01; 4(1):65-78.. View in PubMed
  • Polystyrene nanoparticle trafficking across MDCK-II. Nanomedicine. 2011 Oct; 7(5):588-94.. 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
  • Alveolar epithelial cell injury due to zinc oxide nanoparticle exposure. Am J Respir Crit Care Med. 2010 Dec 01; 182(11):1398-409.. View in PubMed
  • More life for a “terminal” cell. Am J Physiol Lung Cell Mol Physiol. 2009 Dec; 297(6):L1042-4.. 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
  • Mechanisms of alveolar epithelial translocation of a defined population of nanoparticles. Am J Respir Cell Mol Biol. 2010 May; 42(5):604-14.. View in PubMed
  • Characterization of mouse alveolar epithelial cell monolayers. Am J Physiol Lung Cell Mol Physiol. 2009 Jun; 296(6):L1051-8.. View in PubMed
  • Conjugation with cationic cell-penetrating peptide increases pulmonary absorption of insulin. Mol Pharm. 2009 Mar-Apr; 6(2):492-503.. View in PubMed
  • GATA-6 mediates transcriptional activation of aquaporin-5 through interactions with Sp1. Am J Physiol Cell Physiol. 2008 Nov; 295(5):C1141-50.. View in PubMed
  • Molecular and functional expression of multidrug resistance-associated protein-1 in primary cultured rat alveolar epithelial cells. J Pharm Sci. 2008 Jun; 97(6):2340-9.. View in PubMed
  • Retention of human bone marrow-derived cells in murine lungs following bleomycin-induced lung injury. Am J Physiol Lung Cell Mol Physiol. 2008 Aug; 295(2):L285-92.. View in PubMed
  • Rat aquaporin-5 4.3-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
  • Polystyrene nanoparticle trafficking across alveolar epithelium. Nanomedicine. 2008 Jun; 4(2):139-45.. View in PubMed
  • Functional characterization and cloning of amino acid transporter B(0,+) (ATB(0,+)) in primary cultured rat pneumocytes. J Cell Physiol. 2008 Mar; 214(3):645-54.. View in PubMed
  • Characterization of protein factor(s) in rat bronchoalveolar lavage fluid that enhance insulin transport via transcytosis across primary rat alveolar epithelial cell monolayers. Eur J Pharm Biopharm. 2008 Aug; 69(3):808-16.. View in PubMed
  • Foxp2 inhibits Nkx2.1-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
  • Expression and biological activity of ABCA1 in alveolar epithelial cells. Am J Respir Cell Mol Biol. 2008 Mar; 38(3):283-92.. View in PubMed
  • Effects of KGF on alveolar epithelial cell transdifferentiation are mediated by JNK signaling. Am J Respir Cell Mol Biol. 2008 Feb; 38(2):239-46.. View in PubMed
  • Nanoparticle effects on rat alveolar epithelial cell monolayer barrier properties. Toxicol In Vitro. 2007 Dec; 21(8):1373-81.. View in PubMed
  • Enhancement of insulin transport across primary rat alveolar epithelial cell monolayers by endogenous cellular factor(s). Pharm Res. 2007 Sep; 24(9):1713-9.. 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
  • SUMOylation attenuates sensitivity toward hypoxia- or desferroxamine-induced injury by modulating adaptive responses in salivary epithelial cells. Am J Pathol. 2006 May; 168(5):1452-63.. View in PubMed
  • Induction of epithelial-mesenchymal transition in alveolar epithelial cells by transforming growth factor-beta1: potential role in idiopathic pulmonary fibrosis. Am J Pathol. 2005 May; 166(5):1321-32.. View in PubMed
  • Development of a lung slice preparation for recording ion channel activity in alveolar epithelial type I cells. Respir Res. 2005 Apr 27; 6:40.. 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
  • Estimation of paracellular conductance of primary rat alveolar epithelial cell monolayers. J Appl Physiol (1985). 2005 Jan; 98(1):138-43.. 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
  • Net absorption of IgG via FcRn-mediated transcytosis across rat alveolar epithelial cell monolayers. Am J Physiol Lung Cell Mol Physiol. 2004 Sep; 287(3):L616-22.. 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
  • The critical care crisis in the United States: a report from the profession. Chest. 2004 Apr; 125(4):1514-7.. View in PubMed
  • Transcytosis of GCSF-transferrin across rat alveolar epithelial cell monolayers. Pharm Res. 2003 Aug; 20(8):1231-8.. View in PubMed
  • Phenotype-dependent synthesis of transferrin receptor in rat alveolar epithelial cell monolayers. Cell Tissue Res. 2003 Jun; 312(3):313-8.. View in PubMed
  • Modulation of ion conductance and active transport by TGF-beta 1 in alveolar epithelial cell monolayers. Am J Physiol Lung Cell Mol Physiol. 2003 Dec; 285(6):L1192-200.. 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
  • Absorption of intact albumin across rat alveolar epithelial cell monolayers. Am J Physiol Lung Cell Mol Physiol. 2003 Mar; 284(3):L458-65.. View in PubMed
  • Historical perspectives on lung edema clearance. J Appl Physiol (1985). 2002 Oct; 93(4):1527-32.. View in PubMed
  • Polarity of alveolar epithelial cell acid-base permeability. Am J Physiol Lung Cell Mol Physiol. 2002 Apr; 282(4):L675-83.. View in PubMed
  • Hypoxia decreases active Na transport across primary rat alveolar epithelial cell monolayers. Am J Physiol Lung Cell Mol Physiol. 2002 Apr; 282(4):L659-65.. 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
  • Vesicular stomatitis virus G-pseudotyped lentivirus vectors mediate efficient apical transduction of polarized quiescent primary alveolar epithelial cells. J Virol. 2001 Dec; 75(23):11747-54.. View in PubMed
  • Re-evaluating the Na(+) conductance of adult rat alveolar type II pneumocytes: evidence for the involvement of cGMP-activated cation channels. J Physiol. 2001 Nov 01; 536(Pt 3):693-701.. View in PubMed
  • Alveolar epithelial transport. Basic science to clinical medicine. Am J Respir Crit Care Med. 2001 Mar; 163(4):1021-9.. View in PubMed
  • A useful in vitro model for transport studies of alveolar epithelial barrier. Pharm Res. 2001 Mar; 18(3):253-5.. View in PubMed
  • Differential regulation of rat aquaporin-5 promoter/enhancer activities in lung and salivary epithelial cells. J Biol Chem. 2000 Aug 25; 275(34):26507-14.. View in PubMed
  • Rates of protein transport across rat alveolar epithelial cell monolayers. J Drug Target. 2000; 7(5):335-42.. View in PubMed
  • Epidermal growth factor regulation in adult rat alveolar type II cells of amiloride-sensitive cation channels. Am J Physiol. 1999 12; 277(6):C1058-65.. View in PubMed
  • Modulation of t1alpha expression with alveolar epithelial cell phenotype in vitro. Am J Physiol. 1998 07; 275(1):L155-64.. View in PubMed
  • Mechanisms of EGF-induced stimulation of sodium reabsorption by alveolar epithelial cells. Am J Physiol. 1998 07; 275(1):C82-92.. View in PubMed
  • Keratinocyte growth factor modulates alveolar epithelial cell phenotype in vitro: expression of aquaporin 5. Am J Respir Cell Mol Biol. 1998 Apr; 18(4):554-61.. View in PubMed
  • Size-dependent dextran transport across rat alveolar epithelial cell monolayers. J Pharm Sci. 1997 Mar; 86(3):305-9.. View in PubMed
  • Effects of Mycobacterium tuberculosis on the bioelectric properties of the alveolar epithelium. Infect Immun. 1997 Feb; 65(2):692-8.. View in PubMed
  • Horseradish peroxidase transport across rat alveolar epithelial cell monolayers. Pharm Res. 1996 Sep; 13(9):1331-5.. View in PubMed
  • Effects of EGF on alveolar epithelial junctional permeability and active sodium transport. Am J Physiol. 1996 Apr; 270(4 Pt 1):L559-65.. View in PubMed
  • Models for investigation of peptide and protein transport across cultured mammalian respiratory epithelial barriers. Pharm Biotechnol. 1996; 8:325-46.. View in PubMed
  • Reversible transdifferentiation of alveolar epithelial cells. Am J Respir Cell Mol Biol. 1995 May; 12(5):497-502.. View in PubMed
  • Basolateral localization of Na(+)-HCO3- cotransporter activity in alveolar epithelial cells. Respir Physiol. 1995 Apr; 100(1):15-24.. View in PubMed
  • Cl(-)-HCO3- exchanger isoform AE2 is restricted to the basolateral surface of alveolar epithelial cell monolayers. Am J Respir Cell Mol Biol. 1995 Feb; 12(2):211-9.. View in PubMed
  • Rat serum inhibits progression of alveolar epithelial cells toward the type I cell phenotype in vitro. Am J Respir Cell Mol Biol. 1995 Jan; 12(1):50-5.. View in PubMed
  • Late appearance of a type I alveolar epithelial cell marker during fetal rat lung development. Histochemistry. 1994 Oct; 102(4):297-304.. View in PubMed
  • Polarized distribution of Na(+)-H+ antiport activity in rat alveolar epithelial cells. Am J Physiol. 1994 Feb; 266(2 Pt 1):L138-47.. View in PubMed
  • Defined medium for primary culture de novo of adult rat alveolar epithelial cells. In Vitro Cell Dev Biol Anim. 1994 Feb; 30.. View in PubMed
  • Measurement of solute fluxes in isolated rat lungs. Respir Physiol. 1993 Mar; 91(2-3):321-34.. View in PubMed
  • Evidence for amiloride-sensitive sodium channels in alveolar epithelial cells. Am J Physiol. 1992 Apr; 262(4 Pt 1):L405-11.. View in PubMed
  • Reactivity of alveolar epithelial cells in primary culture with type I cell monoclonal antibodies. Am J Respir Cell Mol Biol. 1992 Mar; 6(3):296-306.. View in PubMed
  • Regulation of intracellular pH in alveolar epithelial cells. Am J Physiol. 1992 Jan; 262(1 Pt 1):L1-14.. View in PubMed