J A Whitsett

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States

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Publications (597)3159.65 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Current treatments for inflammation associated with bronchopulmonary dysplasia fail to show clinical efficacy. Foxm1, a transcription factor of the Forkhead box family, is a critical mediator of lung development and carcinogenesis, but its role in bronchopulmonary dysplasia-associated pulmonary inflammation is unknown. Immunohistochemistry and RNA analysis were used to assess Foxm1 in lung tissue from hyperoxia-treated mice and patients with bronchopulmonary dysplasia. LysM-Cre/Foxm1-/- mice, in which Foxm1 was deleted from myeloid-derived inflammatory cells, including macrophages, monocytes and neutrophils, were exposed to neonatal hyperoxia causing lung injury and remodeling. Measurements of lung function and flow cytometry were used to evaluate effects of Foxm1 deletion on pulmonary inflammation and repair. Increased Foxm1 expression was observed in pulmonary macrophages of hyperoxia-exposed mice and lung tissue from patients with bronchopulmonary dysplasia. After hyperoxia, deletion of Foxm1 from the myeloid cell lineage decreased numbers of interstitial macrophages (CD45+CD11b+Ly6C-Ly6G-F4/80+CD68-) and impaired alveologenesis and lung function. The exaggerated bronchopulmonary dysplasia-like phenotype observed in hyperoxia-exposed LysM-Cre/Foxm1-/- mice was associated with increased expression of neutrophil-derived myeloperoxidase, proteinase 3 and cathepsin-g, all of which are critical for lung remodeling and inflammation. Our data demonstrate that Foxm1 influences pulmonary inflammatory responses to hyperoxia, inhibiting neutrophil-derived enzymes and enhancing monocytic responses that limit alveolar injury and remodeling in neonatal lungs.
    American Journal of Respiratory Cell and Molecular Biology 10/2014; · 4.15 Impact Factor
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    ABSTRACT: SAM-pointed domain-containing ETS transcription factor (SPDEF) is expressed in normal prostate epithelium. While its expression changes during prostate carcinogenesis (PCa), the role of SPDEF in prostate cancer remains controversial due to the lack of genetic mouse models. In present study, we generated transgenic mice with the loss- or gain-of-function of SPDEF in prostate epithelium to demonstrate that SPDEF functions as tumor suppressor in prostate cancer. Loss of SPDEF increased cancer progression and tumor cell proliferation, whereas over-expression of SPDEF in prostate epithelium inhibited carcinogenesis and reduced tumor cell proliferation in vivo and in vitro. Transgenic over-expression of SPDEF inhibited mRNA and protein levels of Foxm1, a transcription factor critical for tumor cell proliferation, and reduced expression of Foxm1 target genes, including Cdc25b, Cyclin B1, Cyclin A2, Plk-1, AuroraB, CKS1 and Topo2alpha. Deletion of SPDEF in transgenic mice and cultures prostate tumor cells increased expression of Foxm1 and its target genes. Furthermore, an inverse correlation between SPDEF and Foxm1 levels was found in human prostate cancers. The two-gene signature of low SPDEF and high FoxM1 predicted poor survival in prostate cancer patients. Mechanistically, SPDEF bound to, and inhibited transcriptional activity of Foxm1 promoter by interfering with the ability of Foxm1 to activate its own promoter through auto-regulatory site located in the -745/-660 bp Foxm1 promoter region. Re-expression of Foxm1 restored cellular proliferation in the SPDEF-positive cancer cells and rescued progression of SPDEF-positive tumors in mouse prostates. Altogether, SPDEF inhibits prostate carcinogenesis by preventing Foxm1-regulated proliferation of prostate tumor cells. The present study identified novel crosstalk between SPDEF tumor suppressor and Foxm1 oncogene and demonstrated that this crosstalk is required for tumor cell proliferation during progression of prostate cancer in vivo.
    PLoS Genetics 09/2014; 10(9):e1004656. · 8.52 Impact Factor
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    ABSTRACT: 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.
    Cell stem cell. 08/2014; 15(2):123-138.
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    ABSTRACT: The SRY-box containing transcription factor Sox17 is required for endoderm formation and vascular morphogenesis during embryonic development. In the lung, Sox17 is expressed in mesenchymal progenitors of the embryonic pulmonary vasculature and is restricted to vascular endothelial cells in the mature lung. Conditional deletion of Sox17 in splanchnic mesenchyme-derivatives using Dermo1-Cre resulted in substantial loss of Sox17 from developing pulmonary vascular endothelial cells and caused pulmonary vascular abnormalities before birth, including pulmonary vein varices, enlarged arteries, and decreased perfusion of the microvasculature. While survival of Dermo1-Cre;Sox17Δ/Δ mice (herein termed Sox17Δ/Δ) was unaffected at E18.5, most Sox17Δ/Δ mice died by 3 weeks of age. After birth, the density of the pulmonary microvasculature was decreased in association with alveolar simplification, biventricular cardiac hypertrophy, and valvular regurgitation. The severity of the postnatal cardiac phenotype was correlated with the severity of pulmonary vasculature abnormalities. Sox17 is required for normal formation of the pulmonary vasculature and postnatal cardiovascular homeostasis.
    Developmental Biology 01/2014; · 3.87 Impact Factor
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    ABSTRACT: Rationale: Goblet cell metaplasia accompanies common pulmonary disorders that are prone to recurrent viral infections. Mechanisms regulating both goblet cell metaplasia and susceptibility to viral infection associated with chronic lung diseases are incompletely understood. Objectives: We sought to identify the role of the transcription factor FOXA3 in regulation of goblet cell metaplasia and pulmonary innate immunity. Methods: FOXA3 was identified in airways from patients with asthma and COPD. We produced transgenic mice conditionally expressing Foxa3 in airway epithelial cells and developed human bronchial epithelial cells expressing Foxa3. Foxa3 regulated genes were identified by immunostaining, Western blotting, and RNA analysis. Direct binding of FOXA3 to target genes was identified by ChIP-seq correlated with RNA-seq. Measurements and Main Results: FOXA3 was highly expressed in airway goblet cells from patients with asthma and COPD. FOXA3 was induced by either IL-13 or rhinovirus. Foxa3 induced goblet cell metaplasia and enhanced expression of a network of genes mediating mucus production. Paradoxically, FOXA3 inhibited rhinovirus-induced interferon production, IRF-3 phosphorylation and IKKε expression and inhibited viral clearance and expression of genes required for antiviral defenses, including MDA5, RIG-I, TLR3, IRF7/9, and NFκB. Conclusions: FOXA3 induces goblet cell metaplasia in response to infection or TH2 stimulation. Suppression of interferon signaling by FOXA3 provides a plausible mechanism that may serve to limit ongoing TH1 inflammation during the resolution of acute viral infection; however, inhibition of innate immunity by FOXA3 may contribute to susceptibility to viral infections associated with chronic lung disorders accompanied by chronic goblet cell metaplasia.
    American Journal of Respiratory and Critical Care Medicine 01/2014; · 11.04 Impact Factor
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    ABSTRACT: Pulmonary surfactant is required for lung function at birth and throughout postnatal life. Defects in the surfactant system are associated with common pulmonary disorders including neonatal respiratory distress syndrome and acute respiratory distress syndrome in children and adults. Lipogenesis is essential for the synthesis of pulmonary surfactant by type II epithelial cells lining the alveoli. This study sought to identify the role of pulmonary epithelial SREBP, a transcriptional regulator of cellular lipid homeostasis, during a critical time period of perinatal lung maturation in the mouse. Genome wide mRNA expression profiling of lung tissue from transgenic mice with epithelial-specific deletions of Scap (ScapΔ/Δ, resulting in inactivation of SREBP signaling) or Insig1 and Insig2 (Insig1/2Δ/Δ, resulting in activation of SREBP signaling) was assessed. Differentially expressed genes responding to SREBP perturbations were identified and subjected to functional enrichment analysis, pathway mapping and literature mining to predict upstream regulators and transcriptional networks regulating surfactant lipid homeostasis. Through comprehensive data analysis and integration, time dependent effects of epithelial SCAP/INSIG/SREBP deletion and defined SCAP/INSIG/SREBP-associated genes, bioprocesses and downstream pathways were identified. SREBP signaling influences epithelial development, cell death and cell proliferation at E17.5, while primarily influencing surfactant physiology, lipid/sterol synthesis, and phospholipid transport after birth. SREBP signaling integrated with the Wnt/β-catenin and glucocorticoid receptor signaling pathways during perinatal lung maturation. SREBP regulates perinatal lung lipogenesis and maturation through multiple mechanisms by interactions with distinct sets of regulatory partners.
    PLoS ONE 01/2014; 9(5):e91376. · 3.53 Impact Factor
  • Jeffrey A Whitsett
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    ABSTRACT: Advances in the physiology, biochemistry, molecular and cell biology of the pulmonary surfactant system transformed the clinical care and outcome of preterm infants with respiratory distress syndrome. The molecular era of surfactant biology provided genetic insights into the pathogenesis of pulmonary disorders, previously termed 'idiopathic', that affect newborn infants, children and adults. Knowledge related to the structure and function of the surfactant proteins and their roles in alveolar homeostasis has provided new diagnostic, prognostic and therapeutic tools to advance our understanding of the causes and treatments of acute and chronic lung diseases. Severe lung disease in newborn infants and older patients is caused by mutations in genes regulating alveolar epithelial cells and surfactant homeostasis. Mutations in genes encoding the surfactant proteins, transcription factors critical for alveolar morphogenesis and surfactant clearance, are now known to play important roles in the pathogenesis of chronic lung diseases. Identification of the genes underlying the diseases of alveolar homeostasis is useful for the diagnosis of lung disease before and after birth. © 2014 S. Karger AG, Basel.
    Neonatology 01/2014; 105(4):337-43. · 2.57 Impact Factor
  • Xiaofei Sun, Amanda Bartos, Jeffrey A Whitsett, Sudhansu K Dey
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    ABSTRACT: Leukemia inhibitory factor (LIF), a downstream target of estrogen, is essential for implantation in mice. LIF function is thought to be mediated by its binding to LIF receptor (LIFR) and recruitment of co-receptor GP130, and this receptor complex then activates STAT1/3. However, the importance of LIFR and GP130 acting via STAT3 in implantation remains uncertain, since constitutive inactivation of Lifr, Gp130 or Stat3 shows embryonic lethality in mice. To address this issue, we generated mice with conditional deletion of uterine Gp130 or Stat3 and show that both GP130 and STAT3 are critical for uterine receptivity and implantation. Implantation failure in these deleted mice is associated with higher uterine estrogenic responses prior to the time of implantation. These heightened estrogenic responses are not due to changes in ovarian hormone levels or expression of their nuclear receptors. In the deleted mice, estrogen responsive gene, Lactoferrin (Ltf), and Mucin 1 (MUC1) protein, were upregulated in the uterus. In addition, P4 responsive genes, Hoxa10 and Indian hedgehog (Ihh), were markedly downregulated in STAT3-inactivated uteri. These changes in uteri of deleted mice were reflected by the failure of differentiation of the luminal epithelium, which is essential for blastocyst attachment.
    Molecular Endocrinology 07/2013; · 4.75 Impact Factor
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    ABSTRACT: Foxa2 is a member of the forkhead family of nuclear transcription factors that is highly expressed in respiratory epithelial cells of the developing and mature lung. Foxa2 is required for normal airway epithelial differentiation, its deletion causing goblet cell metaplasia and Th2-mediated pulmonary inflammation during postnatal development. Foxa2 expression is inhibited during aeroallergen sensitization, and after stimulation with Th2 cytokines, where its loss is associated with goblet cell metaplasia. Mechanisms by which Foxa2 controls airway epithelial differentiation and Th2 immunity are incompletely known. During the first two weeks after birth, loss of Foxa2 increased the production of leukotrienes (LTs) and Th2 cytokines in the lung of Foxa2 gene targeted mice. Foxa2 expression inhibited Alox15 and increased Alox5 transcription, each encoding key lipoxygenases associated with asthma. Inhibition of the cysteinyl LTs (CysLTs) signaling pathway by Montelukast inhibited interleukin (IL)-4, IL-5, eotaxin-2, and RANTES expression in the developing lung of Foxa2 gene targeted mice. Montelukast inhibited expression of genes regulating mucous metaplasia, including Spdef, Muc5ac, Foxa3, and Arg2. Foxa2 plays a cell autonomous role in the respiratory epithelium and is required for suppression of Th2 immunity and mucus metaplasia in the developing lung in a process regulated in part by its regulation of the CysLT pathway.
    American Journal of Respiratory Cell and Molecular Biology 07/2013; · 4.15 Impact Factor
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    ABSTRACT: A multi-disciplinary scientific conference focused on diffuse and interstitial lung diseases in children was held in La Jolla, CA in June 2012. The conference brought together clinicians (including Pediatric and Adult Pulmonologists, Neonatologists, Pathologists, and Radiologists), clinical researchers, basic scientists, government agency representatives, patient advocates, as well as children affected by diffuse lung disease (DLD) and their families, to review recent scientific developments and emerging concepts in the pathophysiology of childhood DLD. Invited speakers discussed translational approaches, including genetics and proteomics, epigenetics and epigenomics, models of DLD, including animal models and induced pluripotent stem cells, and regenerative medicine approaches. The presentations of the invited speakers are summarized here. Pediatr Pulmonol. © 2013 Wiley Periodicals, Inc.
    Pediatric Pulmonology 06/2013; · 2.38 Impact Factor
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    ABSTRACT: Goblet cell numbers decrease within the conjunctival epithelium in drying and cicatrizing ocular surface diseases. Factors regulating goblet cell differentiation in conjunctival epithelium are unknown. Recent data indicate that the transcription factor SAM-pointed domain epithelial-specific transcription factor (Spdef) is essential for goblet cell differentiation in tracheobronchial and gastrointestinal epithelium of mice. Using Spdef(-/-) mice, we determined that Spdef is required for conjunctival goblet cell differentiation and that Spdef(-/-) mice, which lack conjunctival goblet cells, have significantly increased corneal surface fluorescein staining and tear volume, a phenotype consistent with dry eye. Microarray analysis of conjunctival epithelium in Spdef(-/-) mice revealed down-regulation of goblet cell-specific genes (Muc5ac, Tff1, Gcnt3). Up-regulated genes included epithelial cell differentiation/keratinization genes (Sprr2h, Tgm1) and proinflammatory genes (Il1-α, Il-1β, Tnf-α), all of which are up-regulated in dry eye. Interestingly, four Wnt pathway genes were down-regulated. SPDEF expression was significantly decreased in the conjunctival epithelium of Sjögren syndrome patients with dry eye and decreased goblet cell mucin expression. These data demonstrate that Spdef is required for conjunctival goblet cell differentiation and down-regulation of SPDEF may play a role in human dry eye with goblet cell loss. Spdef(-/-) mice have an ocular surface phenotype similar to that in moderate dry eye, providing a new, more convenient model for the disease.
    American Journal Of Pathology 05/2013; · 4.60 Impact Factor
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    ABSTRACT: Pulmonary surfactant levels within the alveoli are tightly regulated to maintain lung volumes and promote efficient gas exchange across the air/blood barrier. Both quantitative and qualitative abnormalities in surfactant are associated with severe lung diseases in children and adults. While the cellular and molecular mechanisms that control surfactant metabolism have been studied intensively, the critical molecular pathway(s) that senses and regulates endogenous surfactant levels within the alveolus have not been identified and constitute a fundamental knowledge gap in the field. In this study, we demonstrate that expression of an orphan G protein-coupled receptor, GPR116, in the murine lung is developmentally regulated, reaching maximal levels one day following birth, and is highly expressed on the apical surface of alveolar type I and type II epithelial cells. To define the physiological role of GPR116 in vivo, mice with a targeted mutation of the Gpr116 locus, Gpr116Δexon17, were generated. Gpr116Δexon17 mice developed a profound accumulation of alveolar surfactant phospholipids at 4 weeks of age (12-fold) that is further increased at 20 weeks of age (30-fold). Surfactant accumulation in Gpr116Δexon17 mice was associated with increased SatPC synthesis at 4 weeks and the presence of enlarged, lipid-laden macrophages, neutrophilia and alveolar destruction at 20 weeks. mRNA microarray analyses indicated that P2RY2, a purinergic receptor known to mediate surfactant secretion, was induced in Gpr116Δexon17 type II cells. Collectively, these data support the concept that GPR116 functions as a molecular sensor of alveolar surfactant lipid pool sizes by regulating surfactant secretion.
    American Journal of Respiratory Cell and Molecular Biology 04/2013; · 4.15 Impact Factor
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    ABSTRACT: Krüppel-like factor 5 regulates pluripotent stem cell self-renewal, but its role in somatic stem cells is unknown. Here we show that Krüppel-like factor 5-deficient haematopoietic stem cells and progenitors fail to engraft after transplantation. This haematopoietic stem cell and progenitor defect is associated with impaired bone marrow homing and lodging and decreased retention in bone marrow, and with decreased adhesion to fibronectin and expression of membrane-bound β1/β2-integrins. In vivo-inducible gain-of-function of Krüppel-like factor 5 in haematopoietic stem cells increases haematopoietic stem cell and progenitor adhesion. The expression of Rab5 family members, mediators of β1/β2-integrin recycling in the early endosome, is decreased in Klf5(Δ/Δ) haematopoietic stem cells and progenitors. Krüppel-like factor 5 binds directly to the promoter of Rab5a/b, and overexpression of Rab5b rescues the expression of activated β1/β2-integrins, adhesion and bone marrow homing of Klf5(Δ/Δ) haematopoietic stem cells and progenitors. Altogether, these data indicate that Krüppel-like factor 5 is indispensable for adhesion, homing, lodging and retention of haematopoietic stem cells and progenitors in the bone marrow through Rab5-dependent post-translational regulation of β1/β2 integrins.
    Nature Communications 04/2013; 4:1660. · 10.74 Impact Factor
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    ABSTRACT: Development of the pulmonary system is essential for terrestrial life. The molecular pathways that regulate this complex process are beginning to be defined, and such knowledge is critical to our understanding of congenital and acquired lung diseases. A recent workshop was convened by the National Heart, Lung, and Blood Institute to discuss the developmental principles that regulate the formation of the pulmonary system. Emerging evidence suggests that key developmental pathways not only regulate proper formation of the pulmonary system but are also reactivated upon postnatal injury and repair and in the pathogenesis of human lung diseases. Molecular understanding of early lung development has also led to new advances in areas such as generation of lung epithelium from pluripotent stem cells. The workshop was organized into four different topics, including early lung cell fate and morphogenesis, mechanisms of lung cell differentiation, tissue interactions in lung development, and environmental impact on early lung development. Critical points were raised, including the importance of epigenetic regulation of lung gene expression, the dearth of knowledge on important mesenchymal lineages within the lung, and the interaction between the developing pulmonary and cardiovascular system. This manuscript describes the summary of the discussion along with general recommendations to overcome the gaps in knowledge in lung developmental biology.
    Annals of the American Thoracic Society. 04/2013; 10(2):S12-6.
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    ABSTRACT: Wntless (Wls), a gene highly conserved across the animal kingdom, encodes for a transmembrane protein that mediates Wnt ligand secretion. Wls is expressed in developing lung, wherein Wnt signaling is necessary for pulmonary morphogenesis. We hypothesize that Wls plays a critical role in modulating Wnt signaling during lung development and therefore affects processes critical for pulmonary morphogenesis. We generated conditional Wls mutant mice utilizing Shh-Cre and Dermo1-Cre mice to delete Wls in the embryonic respiratory epithelium and mesenchyme, respectively. Epithelial deletion of Wls disrupted lung branching morphogenesis, peripheral lung development and pulmonary endothelial differentiation. Epithelial Wls mutant mice died at birth due to respiratory failure caused by lung hypoplasia and pulmonary hemorrhage. In the lungs of these mice, VEGF and Tie2-angiopoietin signaling pathways, which mediate vascular development, were downregulated from early stages of development. In contrast, deletion of Wls in mesenchymal cells of the developing lung did not alter branching morphogenesis or early mesenchymal differentiation. In vitro assays support the concept that Wls acts in part via Wnt5a to regulate pulmonary vascular development. We conclude that epithelial Wls modulates Wnt ligand activities critical for pulmonary vascular differentiation and peripheral lung morphogenesis. These studies provide a new framework for understanding the molecular mechanisms underlying normal pulmonary vasculature formation and the dysmorphic pulmonary vasculature development associated with congenital lung disease.
    Developmental Biology 03/2013; · 3.87 Impact Factor
  • Developmental Biology 03/2013; 375(2):128. · 3.87 Impact Factor
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    Developmental Biology 03/2013; 375(2):128. · 3.87 Impact Factor
  • Wan H, Liu C, Wert SE, Xu W, Liao Y, Zheng Y, Whitsett JA
    Developmental Biology 02/2013; 374(1):46. · 3.87 Impact Factor
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    Wan H, Liu C, Wert SE, Xu W, Liao Y, Zheng Y, Whitsett JA
    Developmental Biology 02/2013; 374(1):46. · 3.87 Impact Factor
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    ABSTRACT: Alveolar epithelial cells (AECs) participate in the pathogenesis of pulmonary fibrosis, producing pro-inflammatory mediators and undergoing epithelial-to-mesenchymal transition (EMT). Herein, we demonstrated the critical role of Forkhead Box M1 (Foxm1) transcription factor in radiation-induced pulmonary fibrosis. Foxm1 was induced in AECs following lung irradiation. Transgenic expression of an activated Foxm1 transcript in AECs enhanced radiation-induced pneumonitis and pulmonary fibrosis, and increased the expression of IL-1β, Ccl2, Cxcl5, Snail1, Zeb1, Zeb2 and Foxf1. Conditional deletion of Foxm1 from respiratory epithelial cells decreased radiation-induced pulmonary fibrosis and prevented the increase in EMT-associated gene expression. siRNA-mediated inhibition of Foxm1 prevented TGF-β-induced EMT in vitro. Foxm1 bound to and increased promoter activity of the Snail1 gene, a critical transcriptional regulator of EMT. Expression of Snail1 restored TGF-β-induced loss of E-cadherin in Foxm1-deficient cells in vitro. Lineage-tracing studies demonstrated that Foxm1 increased EMT during radiation-induced pulmonary fibrosis in vivo. Foxm1 is required for radiation-induced pulmonary fibrosis by enhancing the expression of genes critical for lung inflammation and EMT.
    The EMBO Journal 01/2013; · 9.82 Impact Factor

Publication Stats

24k Citations
3,159.65 Total Impact Points

Institutions

  • 1984–2014
    • Cincinnati Children's Hospital Medical Center
      • • Perinatal Institute
      • • Division of Pulmonary Biology
      • • Division of Reproductive Sciences
      Cincinnati, Ohio, United States
  • 1981–2012
    • University of Cincinnati
      • • Department of Environmental Health
      • • Department of Pediatrics
      • • Division of Pulmonary, Critical Care & Sleep Medicine
      • • College of Medicine
      Cincinnati, Ohio, United States
  • 2000–2010
    • Johns Hopkins University
      • Department of Pediatrics
      Baltimore, MD, United States
    • University of Colorado
      • Division of Pulmonary Sciences and Critical Care Medicine
      Denver, CO, United States
    • Boston Children's Hospital
      • Department of Pathology
      Boston, Massachusetts, United States
  • 2007–2009
    • MRC National Institute for Medical Research
      • Division of Developmental Neurobiology
      Londinium, England, United Kingdom
    • University of Oslo
      • Department of Paediatrics
      Oslo, Oslo, Norway
  • 2008
    • Boston University
      • Pulmonary Center
      Boston, MA, United States
    • University of Chicago
      • Department of Medicine
      Chicago, Illinois, United States
    • The University of Manchester
      • Faculty of Life Sciences
      Manchester, England, United Kingdom
  • 2002–2008
    • University of Pennsylvania
      • Department of Medicine
      Philadelphia, PA, United States
  • 2006
    • Osaka City University
      Ōsaka, Ōsaka, Japan
  • 2004
    • Osaka University
      • Division of Environmental and Molecular Medicine
      Ōsaka-shi, Osaka-fu, Japan
  • 2002–2004
    • University of Illinois at Chicago
      • Department of Biochemistry and Molecular Genetics (Chicago)
      Chicago, IL, United States
  • 2003
    • University of North Carolina at Chapel Hill
      • Department of Pediatrics
      Chapel Hill, NC, United States
    • Stazione Zoologica Anton Dohrn di Napoli
      Napoli, Campania, Italy
  • 1992–2003
    • Vanderbilt University
      • Department of Pediatrics
      Nashville, Michigan, United States
    • Oregon Health and Science University
      • Department of Medicine
      Portland, OR, United States
    • University of California, Davis
      • School of Veterinary Medicine
      Davis, CA, United States
  • 1999–2001
    • State University of New York Downstate Medical Center
      • Department of Pathology
      Brooklyn, NY, United States
  • 1998
    • University of Adelaide
      • Department of Physiology
      Adelaide, South Australia, Australia
    • University of Iowa
      • Department of Pediatrics
      Iowa City, IA, United States
  • 1997
    • University of California, Los Angeles
      • Department of Pediatrics
      Los Angeles, CA, United States
  • 1996
    • Dana-Farber Cancer Institute
      Boston, Massachusetts, United States
  • 1993–1996
    • Harbor-UCLA Medical Center
      • Department of Pediatrics
      Torrance, CA, United States
  • 1994–1995
    • Yale University
      • • Section of Pulmonary and Critical Care Medicine
      • • Department of Internal Medicine
      New Haven, CT, United States
    • Whitehead Institute for Biomedical Research
      Cambridge, Massachusetts, United States
    • Washington University in St. Louis
      • Department of Pediatrics
      Saint Louis, MO, United States
  • 1993–1994
    • George Washington University
      Washington, Washington, D.C., United States
  • 1990–1994
    • Children's National Medical Center
      Washington, Washington, D.C., United States
    • Hospital of the University of Pennsylvania
      • Department of Pediatrics
      Philadelphia, Pennsylvania, United States
    • The Naval Aerospace Medical Institute
      Pensacola, Florida, United States
    • University of Wisconsin, Madison
      • Department of Pediatrics
      Madison, MS, United States
  • 1991
    • University of Rochester
      • Department of Pediatrics
      Rochester, NY, United States
    • Mercy Hospital St. Louis
      San Luis, Missouri, United States
  • 1989
    • The Ohio State University
      • Department of Pediatrics
      Columbus, OH, United States
    • University of Southern California
      • School of Dentistry
      Los Angeles, CA, United States