CCMB Faculty

CSA103, HSC 9062
(323)669-4180 Voice
(323)671-3613 Fax
dwarburton@chla.usc.edu

David Warburton

M.D.

Professor

Education Experience Honors & Awards Projects Publications

Education

INSTITUTION AND LOCATION	DEGREE	YEAR(s)	FIELD OF STUDY
University of London, U.K.	D.Sc.	2000	Science
Royal College of Physicians of Edinburgh	FRCP	1996	Medicine
Royal College of Physicians, UK	MRCP	1975	Pediatrics
University of London, U.K.	MB, BS	1973	Medicine
University of London, U.K.	B.Sc (Honours)	1970	Physiology

Research & Professional Experience

2002-present	Vice-Chair, Department of Pediatric Surgery, Childrens Hospital Los Angeles, Los Angeles, CA
1995-present	Professor of Craniofacial Molecular Biology, School of Dentistry, University of southern California, Los Angeles, CA
1994-present	Professor of Surgery, School of Medicine, University of southern California, Los Angeles, CA
1990-present	Professor of Pediatrics, School of Medicine, University of southern California, Los Angeles, CA
1984-1990	Associate Professor of Pediatrics, School of Medicine, University of southern California, Los Angeles, CA
1979-1983	Assistant Professor of Pediatrics, School of Medicine, University of southern California, Los Angeles, CA
1977-1979	Fellow in Neonatology, Women & Infants Hospital of RI, Brown University
1976-1977	Pediatric Resident, Boston Children's Hospital, Harvard University
1973-1976	House Officer in Paediatrics, University of London
1970-1973	Tutor in Physiology, University of London
1968-1970	MRC Scholar in Physiology, University of London

Academic Honors and Awards

2003	NHLBI/SDB Symposium on Stem Cells and the Lung: Organizer and Chair
2002	NHLBI Workshop on Cell Based Therapies: Chair
2000	Rothschild-Yvette Mayant Award, Insitut Curie, Paris, France
1998	NHLBI Workshop on Molecular Embryology of the Lung: Chair
1998-2003	NIH PO1HL60231 "Molecular basis of lung morphogenesis, injury and repair"
1996-1999	NIH Fogarty Center, Senior International Fellowship with David Lane, FRS
1991-2005	NIH RO1HL44060 "Developmental type II pneumocyte protein phosphorylation".
1991-2005	NIH RO1HL44977 "Autocrine & paracrine factors regulating lung morphogenesis".
1995	NHLBI/NCI Workshop on Stem cells in lung growth, injury repair and cancer.
1993-present	NIH, DRG Human Embryology & Development Study Section, ad hoc.
1993	NHLBI Pulmonary Disease Advisory Committee, ad hoc (SCORs: Program Review).
1993	NHLBI/ NCI Workshop on Determinants of lung growth: development versus cancer.
1992	NHLBI Symposium on Molecular Embryology and Lung Morphogenesis (organizer).
1992	Russell H. Smith Award for Innovation in Pediatric Biomedical Research,
1991	NIH, DRG Lung Cell and Molecular Biology Study Section, ad hoc.
1990-1991	NIH, NHLBI Pulmonary SCOR Grants, Review Coordinating Committee, adhoc.
1987-1988	NIH Fogarty Center, Senior International Fellowship with Philip Cohen, FRS.
1982-1987	NIH SERCA 5K01 AM01130: Effects of maternal diabetes on fetal lung.

Research Projects During the Last 3 Years

"Autocrine/Paracrine Growth Factors & Lung Morphogenesis "

Principal Investigator: David Warburton
Sponsor: National Heart, Lung, and Blood Institute
Period: 3/01/1991-02/28/2005
The major goal of this project is to understand basic molecular mechanisms that modulate early murine embryonic lung organogenesis may suggest new ways of enhancing lung development or of inducing lung regeneration in human infants with pulmonary hypoplasia, bronchopulmonary dysplasia or even in older humans with decreased lung capacity.

"Developmental type II pneumocyte protein phosphorylation"

Principal Investigator: David Warburton
Sponsor: National Heart, Lung, and Blood Institute
Period: 2/01/1991-01/31/2005
This grant program has the objective of determining the protein phosphorylation and dephosphorylation mechanisms that regulate type II pneumocyte function, particularly proliferation and differentiation in fetal, adult and transformed alveolar epithelial cells.

"Epithelial and endothelial crosstalk in lung organogenesis"

Principal Investigator: David Warburton
Sponsor: National Heart, Lung, and Blood Institute
Period: 10/02/2003-9/30/2007
This grant seeks to determine the role of VEGF and FGF signaling in epithelial and endothelial cell communication during lung morphogenesis.

Publications(selected from more than 200)

Chen C, Chen H, Sun J, Bringas Jr P, Chen Y, Warburton D, Shi W. (2005). Smad1 expression and function during mouse embryonic lung branching morphogenesis. Am J Physiol Lung Cell Mol Physiol. In Press

Chen H, Sun J, Buckley S, Chen C, Warburton D, Wang XF, Shi W. (2004). Abnormal Mouse Lung Alveolarization Caused by Smad3 Deficiency Is A Developmental Antecedent of Centrilobular Emphysema. Am J Physiol Lung Cell Mol Physiol. In Press

Ding W, Bellusci S, Shi W, Warburton D. (2004). Genomic structure and promoter characterization of the human Sprouty4 gene, a novel regulator of lung morphogenesis. Am J Physiol Lung Cell Mol Physiol. 287(1):L52-9

Shi W, Chen H, Sun J, Chen C, Zhao J, Wang Y, Anderson KD, Warburton D. (2004). Overexpression of Smurf1 Negatively Regulates Mouse Embryonic Lung Branching Morphogenesis by Specifically Reducing Smad1 and Smad5 Proteins. Am J Physiol Lung Cell Mol Physiol. 286:L293-300

Buckley S, Shi W, Driscoll B, Anderson KD, Warburton D. (2004). BMP4 signaling induces senescence and modulates the oncogenic phenotype of A549 lung adenocarcinoma cells. Am J Physiol Lung Cell Mol Physiol. 286:L81-6

Ding W, Bellusci S, Shi W, Warburton D. (2003). Functional analysis of the human Sprouty2 gene promoter. Gene 322:175-85.

Gauldie J, Galt T, Bonniaud P, Robbins C, Kelly M, Warburton D. (2003). Transfer of the active form of transforming growth factor-beta1 gene to newborn rat lung induces changes consistent with Bronchopulmonary Dysplasia. Am J Pathol 163:2575-2584.

Burns RC, Fairbanks TJ, Sala F, DeLanghe S, Mailleux A, Thiery JP, Dickson C, Itoh N, Warburton D, Anderson KD, Bellusci S. (2003). Requirement for fibroblast growth factor 10 or fiberoblast growth factor receptor 2-IIIb signaling for cecal development in mouse. Dev Biol 265:61-74.

Warburton D, Bellusci S, Del Moral PM, Kaartinen V, Lee M, Tefft D, Shi W. (2003). Growth factor signaling in lung morphogenetic centers: automaticity, stereotypy and symmetry. Respir Res. 4(1):5.

Flores-Delgado G, Anderson KD, Warburton D. (2003). Nongenomic estrogen action regulates tyrosine phosphatase activity and tuberin stability. Mol Cell Endocrinol;199(1-2):143-51

Huang EY, Wu H, Island ER, Chong SS, Warburton D, Anderson KD, Tuan TL. (2002). Differential expression of urokinase-type plasminogen activator and plasminogen activator inhibitor-1 in early and late gestational mouse skin and skin wounds. Wound Repair Regen;10(6):387-96

Buckley S, Warburton D. (2002). Dynamics of metalloproteinase-2 and -9, TGF-beta, and uPA activities during normoxic vs. hyperoxic alveolarization. Am J Physiol Lung Cell Mol Physiol;283(4):L747-54

Leinwand MJ, Tefft JD, Zhao J, Coleman C, Anderson KD, Warburton D. (2002). Nitrofen inhibition of pulmonary growth and development occurs in the early embryonic mouse. J Pediatr Surg;37(9):1263-8

Leinwand MJ, Zhao J, Tefft JD, Anderson KD, Warburton D. (2002). Murine nitrofen-induced pulmonary hypoplasia does not involve induction of TGF-beta signaling. J Pediatr Surg;37(8):1123-7

Tefft D, Lee M, Smith S, Crowe DL, Bellusci S, Warburton D. (2002). mSprouty2 inhibits FGF10-activated MAP kinase by differentially binding to upstream target proteins. Am J Physiol Lung Cell Mol Physiol 283(4):L700-L706

Warburton D. (2002). Sound the tocsin! Beware adverse effects of lung inflammation early in gestation. Am. J. Resp. Crit. Care Med. 165:741-2

Zhao J, Shi W, Wang YL, Chen H, Bringas P Jr, Datto MB, Frederick JP, Wang XF, Warburton D (2002). Smad3 deficiency attenuates bleomycin-induced pulmonary fibrosis in mice. Am J Physiol Lung Cell Mol Physiol 282(3):L585-93

Warburton D, Tefft D, Mailleux A, Bellusci S, Thiery JP, Zhao J, Buckley S, Shi W, Driscoll B (2001). Do lung remodeling, repair, and regeneration recapitulate respiratory ontogeny? Am J Respir Crit Care Med 2001 Nov 15;164(10 Pt 2):S59-62

Zhao J, Chen H, Wang YL, Warburton D (2001). Abrogation of tumor necrosis factor-alpha converting enzyme inhibits embryonic lung morphogenesis in culture. Int J Dev Biol 45(4):623-31

Buckley S, Driscoll B, Shi W, Anderson K, Warburton D. (2001). Migration and gelatinases in cultured fetal, adult and hyperoxic alveolar epithelial cells. Amer J. Physiol. 281:L427-34

Acosta JM, Thebaud B, Castillo C, Mailleux A, Tefft D, Wuenschell C, Anderson KD, Bourbon J, Thiery JP, Bellusci S, Warburton D (2001). Novel mechanisms in murine nitrofen-induced pulmonary hypoplasia: FGF10 rescue in culture. Am J Physiol Lung Cell Mol Physiol. 281(1):L250-7.

Acosta JM, Chai Y, Meara JG, Bringas P, Anderson KD, Warburton D. (2001). Prenatal exposure to nitrofen induces Fryns phenotype in mice. Ann. Plast. Surg. 46:635-40

Flores-Delgado G, Bringas P, Buckley S, Anderson KD, Warburton D. (2001). Nongenomic estrogen action in human lung myofibroblasts. Biochem. Biophys. Res. Commun. 283:661-7

Phagoo SB, Reddi K, Anderson KD, Leeb-Lundberg LM, Warburton D. (2001). Bradykinin B1 receptor up-regulation by interleukin-1 beta and B1 agonists occurs through independent and synergistic signaling mechanisms in human lung fibroblasts. J. Pharm. Exp. Ther. 298:77-885

Zhao J, Chen H, Peschon JJ, Shi W, Zhang Y, Frank SJ, Warburton D (2001). Pulmonary hypoplasia in mice lacking tumor necrosis factor- converting enzyme indicates an indispensable role for cell surface protein shedding during embryonic lung branching morphogenesis. Dev Biol 232(1):204-18

Mailleux AA, Tefft D, Ndiaye D, Itoh N, Thiery J-P, Warburton D, Bellusci S. (2001). Evidence that SPROUTY2 functions as an inhibitor of mouse embryonic lung morphogenesis. Mechanisms of Development 102:81-94(Cover picture)

Shi W, Zhao J, Anderson KD, Warburton D. (2001). Gremlin negatively modulates BMP-4 induction of embryonic lung branching morphogenesis. Amer. J. Physiol. Lung Cell Mol. Physiol. 280:L1030-1039

Driscoll B, Buckley S, Bui KC, Anderson KD, Warburton D. (2000). Telomerase in alveolar epithelial development and repair. Amer. J. Physiol. Lung Cell. Mol. Physiol. 279:L1191-8

Schwarz MA, Zhang, F, Gebb S, Starnes V, Warburton D. (2000). Endothelial monocyte activating polypeptide II inhibits lung neovascularization and airway epithelial morphogenesis. Mech. Dev. 95(1-2):123-132.

Ben-Ari J, Makhoul IR, Dorio RJ, Buckley S, Warburton D, Walker SM. (2000). Cytokine response during hyperoxia: sequential production of pulmonary tumor necrosis factor and interleukin-6 in neonatal rats. Isr. Med. Assoc. J. 2(5): 365-369.

Liu J, Shi W, Warburton D. (2000). A cysteine residue in the helix-loop-helix domain of Id2 is critical for homodimerization and function. Biochem. Biophys. Res. Commun. 273(3): 1042-1047

Lecart C, Cayabyab R, Buckley S, Morrison J, Kwong KY, Warburton D, Ramanathan R, Jones CA, Minoo P. (2000). Bioactive transforming growth factor-beta in the lungs of extremely low birthweight neonates predicts the need for home oxygen supplementation. Biol. Neonate 77(4): 217-223.

Zhao J, Shi W, Chen H, Warburton D (2000). Smad7 and Smad6 Differentially Modulate TGFb-Induced Inhibition of Embryonic Lung Morphogenesis. J Biol Chem 275(31):23992-7

Zhao J, Crowe DL, Castillo C, Wuenschell C, Chai Y, Warburton D (2000). Smad7 is a TGF-ß-inducible attenuator of Smad2/3-mediated inhibition of embryonic lung morphogenesis. Mechanisms of Development 93: 71-81.

Warburton D, Schwarz M, Tefft D, Flores-Delgado G, Anderson KD, Cardoso WV. (2000). The Molecular Basis of Lung Morphogenesis. Mech. Dev. 92:55-81(Review)

Island E, Wu H, Warburton D, Anderson KD, Tuan T-L. (1999). Developmental differences in the expression and modulation of extracellular matrix proteases and inhibitors in mouse skin fibroblasts. Wound Repair Regen. 7:467-76

Shi W, Heisterkamp N, Groffen J, Zhao J, Warburton D, Kaartinen V. (1999). TGF-beta3 null mutation does not abrogate fetal lung maturation in vivo by glucocorticoids. Amer. J. Physiol., 277:L1205-13

Zhao J, Sime PJ, Bringas P Jr, Tefft JD, Buckley S, Bu D, Gauldie J, Warburton D (1999). Spatial-specific TGF-beta1 adenoviral expression determines morphogenetic phenotypes in embryonic mouse lung. Eur J Cell Biol 78: 715-725

Chai Y, Zhao J, Mogharei A, Bringas P, Liu Y-H, Shuler C and Warburton D. (1999). Inhibition of transforming growth factor beta type II receptor signaling accelerates tooth formation in first bronchial arch explants. Mech. Dev., 86:63-74

Buckley S, Driscoll B, Barsky L, Weinberg K, Anderson KD, Warburton D. (1999). ERK activation protects against DNA damage and apoptosis in hyperoxic rat AEC2. Am. J. Physiol.: Lung Cell Mol. Physiol. 277:L159-66

Driscoll BD, Buckley S, Anderson KD, Warburton D. (1999). Abrogation of cyclin D1 predisposes lung cancer cells to apoptotic cell death. Amer. J. Physiol.: Lung Cell Mol. Physiol, 276:L679-87

Tefft JD, Lee M, Smith S, Leinwand M, Zhao J, Bringas P Jr, Crowe DL, Warburton D (1999). Conserved function of mSpry-2, a murine homolog of Drosophila sprouty, which negatively modulates respiratory organogenesis. Curr Biol 9(4):219-22

Schwarz M, Lee M, Zhao J, Zhang F, Jin Y, Smith S, Bhuva J, Stern D, Warburton D, Starnes V. (1999). EMAP II: a modulator of neovascularization in the developing lung. Amer. J. Physiol: Lung Cell Mol. Physiol. 20:L365-375

Warburton D, Zhao J, Berberich MA, Bernfield M (1999) Molecular embryology of the lung: then, now, and in the future. Am J Physiol 76(5 Pt 1):L697-704

Zhao J, Sime PJ, Bringas P Jr, Gauldie J, Warburton D (1999). Adenovirus-mediated decorin gene transfer prevents TGF-beta-induced inhibition of lung morphogenesis. Am J Physiol 277(2 Pt 1):L412-22

Zhao J, Sime PJ, Bringas P Jr, Gauldie J, Warburton D (1998). Epithelium-specific adenoviral transfer of a dominant-negative mutant TGF-beta type II receptor stimulates embryonic lung branching morphogenesis in culture and potentiates EGF and PDGF-AA. Mech Dev 72(1-2):89-100

Lee MK, Zhao J, Smith SM, Tefft JD, Bringas P, Hwang C, Warburton D. (1998). The Shc 66 and 46 kD isoforms are differentially downregulated at parturition in the fetal mouse lung. Pediatr. Res. 44:850-859

Zhao J, Tefft JD, Lee M, Smith S, Warburton D (1998). Abrogation of betaglycan attenuates TGF-beta-mediated inhibition of embryonic murine lung branching morphogenesis in culture. Mech Dev 1998 Jul;75(1-2):67-79

Buckley S, Driscoll DB, Anderson KD, Warburton D. (1998). Apoptosis and DNA damage in AEC2 cultured from hyperoxic rats. Amer. J. Physiol. Lung Cell. Mol. Physiol. 274:L714-720

Flores-Delgado G, Bringas P, Warburton D. (1998). Laminin 2 is a selective adhesion substrate for myofibroblasts in fetal mouse lung. Amer. J. Physiol. Lung Cell. Mol. Biol., 275:L622-630

Warburton D, Wuenschell C, Flores-Delgado G, Anderson K (1998). Commitment and differentiation of lung cell lineages. Biochemistry and Cell Biology 76: 971-995.

Coleman C, Zhao J, Gupta M, Buckley S, Tefft JD, Wuenschell CW, Minoo P, Anderson KD, Warburton D (1998). Inhibition of vascular and epithelial differentiation in murine nitrofen-induced diaphragmatic hernia. American Journal of Physiology 274: L636-646.

Coleman C, Tuan TL, Buckley S, Anderson KD, Warburton D. (1998). Contractility, TGF-beta and plasmin in fetal skin fibroblasts: role in scarless wound healing. Pediatr. Res., 43:403-409

Zhao JS, Lee M, Smith S, Warburton D. (1998). Abrogation of Smad2 and Smad3 or Smad4 expression positively regulates lung branching morphogenesis in culture. Devel. Biol. 194:182-195

Wuenschell CW, Zhao J, Tefft JD, Warburton D (1998). Nicotine stimulates branching and expression of SP-A and SP-C mRNAs in embryonic mouse lung culture. American Journal of Physiology 247: L165-170.

Zhao J, Warburton D (1998). Matrix Gla protein gene expression is induced by transforming growth factor-beta in embryonic lung culture. Am J Physiol 273(1 Pt 1):L282-7

Wuenschell CW, Sunday ME, Singh G, Minoo P, Slavkin HC, Warburton D (1996). Embryonic mouse lung epithelial progenitor cells co-express immunohistochemical markers of diverse mature cell lineages. Journal of Histochemistry and Cytochemistry 44: 113-123.

Shiratori M, Oshika E, Ung LP, Singh G, Shinozuka H, Warburton D, Michalopoulos G, Katyal S (1996). Keratinocyte growth factor and embryonic rat lung morphogenesis. Amer. J. Resp. Cell. Mol. Biol., 15:328-338

Buckley S, Bui KC, Hussain M, Warburton D (1996). Dynamics of TGF-beta 3 peptide activity during alveolar epithelial type 2 cell recovery from hyperoxic lung injury. Amer. J. Physiol. Lung Cell. Mol. Physiol.,15:L54-60

Wu F, Buckley S, Bui KC, Yee A, Wu HY, Liu J, Warburton D (1996). Cell cycle arrest in G0/G1 phase by contact inhibition and TGF-beta 1 in mink Mv1Lu lung epithelial cells. Amer. J. Physiol. Lung Cell. Mol. Phsyiol. 14:L879-888.

Hall FL, Benya PD, Padilla SR, Carbonaro-Hall D, Williams R, Buckley S, Warburton D (1996). Transforming growth factor-beta type-II receptor signalling: intrinsic/associated casein kinase activity, receptor interactions and functional effects of blocking antibodies. Biochem. J. 316:303-310.

Gordon EM, Venkatesan N, Salazar R, Tang H, Schmeidler-Sapiro K, Buckley S, Warburton D, Hall FL (1996). Factor XII-induced mitogenesis is mediated via a distinct signal transduction pathway that activates a mitogen-activated protein kinase. Proc. Nat. Acad. Sci., USA 93:2174-2179.

Wuenschell CW, Sunday ME, Singh G, Minoo P, Slavkin HC, Warburton D (1996). Embryonic mouse lung epithelial progenitor cells co-express immunohistochemical markers of diverse mature cell lineages. J. Histochem. Cytochem. 44:113-123.

Kaartinen V, Voncken JW, Shuler C, Warburton D, Bu D, Heisterkamp N, Groffen J (1995). Abnormal lung development and cleft palate in mice lacking TGF-beta 3 indicates defects of epithelial-mesenchymal interaction. Nature Genetics 11:415-421.

Minoo P, Hamdan H, Bu D, Warburton D, Stepanik P, deLemos R (1995). TTF-1 regulates lung epithelial morphogenesis. Developmental Biology 172:694-698.

Bui KC, Buckley S, Wu F, Uhal B, Joshi I, Liu J, Hussain M, Makhoul I, Warburton D (1995). Induction of A- and D-type cyclins and cdc2 kinase activity during recovery from short-term hyperoxic lung injury. Amer. J. Physiol. Lung Cell Mol. Biol., 268:L625-635.

Wu F, Bui KC, Buckley S, Warburton D (1994). Cell cycle-dependent expression of cyclin D1 and a 45 kD protein in human A549 lung carcinoma cells. Amer. J. Resp. Cell Mol. Biol., 10:437-447.

Shum L, Sakakura Y, Bringas P, Luo W, Snead ML, Mayo M, Crohin C, Millar S, Werb Z, Buckley S, Hall FL, Warburton D, Slavkin HC (1993). EGF abrogation induced fusilli-form dysmorphogenesis of Meckel's cartilage during embryonic mouse mandibular morphogenesis in vitro. Development 118:903-917.

Williams RT, Sanghera S, Warburton D, Pelech S, Hall FL (1993). Identification of a human EGF receptor associated protein kinase as a new member of the mitogen-activated protein kinase/ extracellular signal-related protein kinase family. J Biol. Chem. 268:18213-18217.

Bui KC, Wu F, Buckley S, Wu L, Williams R, Carbonaro-Hall D, Hall FL, Warburton D (1993). Cyclin A expression in normal and transformed alveolar epithelial cells. Amer. J. Resp. Cell Mol. Biol., 9:115-125.

Seth R, Shum L, Wu F, Wuenschell CW, Hall FL, Slavkin HC, Warburton D (1993). Role of epidermal growth factor expression in early mouse embryo lung branching morphogenesis in culture: antisense oligodeoxynucleotide inhibitory strategy. Developmental Biology 158: 555-559.

Warburton D, Lee M, Berberich MA, Bernfield M (1993). Molecular embryology and the study of lung development. Amer J Resp Cell Mol Biol. 9:5-9.

Carbonaro-Hall D, Williams R, Wu L, Warburton D, Zeichner-David M, MacDougall M, Tolo V, Hall F (1993).G1 expression and multistage dynamics of cyclin A in human osteosarcoma cells. Oncogene, 8:1649-1659.

Warburton D, Seth R, Shum L, Horcher PG, Hall FL, Werb Z, Slavkin HC (1992). Epigenetic role of epidermal growth factor expression and signalling in embryonic mouse lung morphogenesis. Developmental Biology, 149:123-133.

Raaberg L, Nexo E, Buckley S, Luo W, Snead ML, Warburton D (1992). Epidermal growth factor transcription, translation and signal transduction in rat type II pneumocytes in culture. Amer. J. Resp. Cell Mol. Biol 6:44-49.

Parton L, Warburton D, Laug W (1992). Plasminogen activator inhibitor type 1 production by rat type II pneumocytes in culture. Amer. J. Resp. Cell Mol. Biol. 6:133-139.

Warburton D, Tayag A, Buckley S, Cosico L, Seth R (1991). Protein phosphorylation and dephosphorylation in type II pneumocytes. Am J Physiol 260(6 Pt 1):L548-54

Last Updated: 02/08/05