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Wei ShiPh.D. Assistant Professor |
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"SMAD-Mediated Signaling During Lung Morphogenesis "
This grant seeks to determine the molecular mechanisms of TGF-beta in regulation of embryonic lung morphogenesis. The specific aims of this grant are: 1) to define the temporo-spatial expression of TGF-beta-specific Smad genes during embryonic lung development; 2) to determine the molecular mechanism of TGF-beta pathway-restricted Smad2 and Smad3 proteins in regulating embryonic pulmonary branching morphogenesis and cytodifferentiation; 3) to define the biological function of inhibitory Smad6 and Smad7 protein in developing lung. "Molecular Mechanism of Lung Branching Morphogenesis"
This grant is focused on determining the mechanisms by which BMP4 induces lung branching morphogenesis in mouse. The specific aims of this grant are: 1) to determine BMP4 inductive effects on branching morphogenesis of E11.5 mouse embryonic lung in the presence and absence of mesenchyme. 2) to define gene expression pattern, specific activation, and biological function of specific BMP4 receptors and downstream Smads during BMP4 induced embryonic lung branching morphogenesis. 3) to determine the biological roles of specific negative regulators (Gremlin, NMA, and Smad6) of BMP4 signaling during embryonic lung branching morphogenesis. "Transforming growth factor-beta3 in pulmonary vessel development"
The general goal of this project is to determine the role of TGF- beta3 in pulmonary blood vessel formation using a TGF-beta3 null mutant mouse model. The specific aims of this study are: 1) to characterize the phenotype of pulmonary blood vessel in TGF-beta3 (-/-) mice; 2) to compare endothelial cell proliferation between wild type and TGF-beta3 (-/-) fetal mouse lungs; and 3) to determine genes regulated by TGF-beta3 in the lung angiogenesis. "TACE-Mediated Ectodomain Shedding in Myocardial Development"
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Chen H, Zhuang F, Liu YH, Xu B, Del Moral P, Deng W, Chai Y, Kolb M, Gauldie J, Warburton D, Moses HL, Shi W. (2008) TGF-beta receptor II in Epithelia Versus Mesenchyme Plays Distinct Role in Developing Lung. Eur Respir J. (In Press) Buckley S, Shi W, Barsky L, Warburton D. (2008). TGF-beta signaling promotes survival and repair in rat alveolar epithelial type 2 cells during recovery after hyperoxic injury. Am J Physiol Lung Cell Mol Physiol. 294(4):L739-48. Sun J, Chen H, Chen C, Whitsett JA, Mishina Y, Bringas P Jr., Ma JC, Warburton D, Shi, W. (2007). Prenatal lung epithelial specific abrogation of Alk3-BMP signaling causes neonatal respiratory distress by disrupting distal airway formation. Am J. Pathology, 172(3):571-82 Sun J, Liu YH, Chen H, Nguyen MP, Mishina Y, Upperman JS, Ford HR, Shi W. (2007) Deficient Alk3-mediated BMP signaling causes prenatal omphalocele-like defect. Biochem Biophys Res Commun. 360:238-43. Liao CP, Zhong C, Saribekyan G, Bading J, Park R, Conti PS, Moats R, Berns A, Shi W, Zhou Z, Nikitin AY, Roy-Burman P. (2007) Mouse models of prostate adenocarcinoma with the capacity to monitor spontaneous carcinogenesis by bioluminescence or fluorescence. Cancer Res. 67:7525-33. Shi W, Bellusci S, Warburton D. (2007). Lung Development and Adult Lung Diseases. Chest. 132:651-656. Ding W, Shi W, Bellusci S, Groffen J, Heisterkamp N, Minoo P, Warburton D. (2007). Sprouty2 downregulation plays a pivotal role in mediating crosstalk between TGF-beta1 signaling and EGF as well as FGF receptor tyrosine kinase-ERK pathways in mesenchymal cells. J Cell Physiol. 212:796-806. Warburton D, Gauldie J, Bellusci S, Shi W. (2006). Lung development and susceptibility to chronic obstructive pulmonary disease. Proc Am Thorac Soc. 3:668-72. Sun J, Zhuang FF, Mullersman JE, Chen H, Robertson EJ, Warburton D, Liu YH, Shi W. (2006). BMP4 activation and secretion are negatively regulated by an intracellular gremlin-BMP4 interaction. J Biol Chem. 281, 29349-56. Del Moral PM, Sala FG, Tefft D, Shi W, Keshet E, Bellusci S, Warburton D. (2005). VEGF-A signaling through Flk-1 is a critical facilitator of early embryonic lung epithelial to endothelial crosstalk and branching morphogenesis. Dev Biol. 290(1):177-88 Warburton D, Shi W. (2005). Lo, and the niche is knit: lysyl oxidase activity and maintenance of lung, aorta, and skin integrity. Am J Pathol. 167(4):921-2. Tefft D, De Langhe SP, Del Moral PM, Sala F, Shi W, Bellusci S, Warburton D. (2005). A novel function for the protein tyrosine phosphatase Shp2 during lung branching morphogenesis. Dev Biol. 282(2):422-31. Warburton D, Bellusci S, De Langhe S, Del Moral PM, Fleury V, Mailleux A, Tefft D, Unbekandt M, Wang K, Shi W. (2005). Molecular mechanisms of early lung specification and branching morphogenesis. Pediatr Res. 57(5 Pt 2):26R-37R. 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. 288(6):L1033-9 Chen H, Sun J, Buckley S, Chen C, Warburton D, Wang XF, Shi W. (2005). Abnormal Mouse Lung Alveolarization Caused by Smad3 Deficiency Is A Developmental Antecedent of Centrilobular Emphysema. Am J Physiol Lung Cell Mol Physiol. 288(4):L683-91 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. Shi W, Chen H, Sun J, Buckley S, Zhao J, Anderson KD, Williams RG, Warburton D. (2003). TACE is required for fetal murine cardiac development and modeling. Dev Biol. 261(2):371-80. 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. 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;164(10 Pt 2):S59-62 Shi W, Zhao J, Anderson KD, Warburton D (2001). Gremlin negatively modulates BMP-4 induction of embryonic mouse lung branching morphogenesis. American Journal of Physiology 280: L1030-L1038 Buckley S, Driscoll B, Shi W, Anderson K, Warburton D (2001). Cell migration and gelatinases in cultured fetal, adult and hyperoxic alveolar epithelial cells. Am J Physiol Lung Cell Mol Physiol;281(2):L427-L434 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. Developmental Biology 232(1):204-218 Liu J, Shi W, Warburton D (2000). A cysteine residue in the helix-loop-helix domain of Id2 is critical for homodimerization and function. Biochemical Biophysical Research Communications 273:1042-1047 Zhao J, Shi W, Chen H, Warburton D (2000). Smad7 and Smad6 Differentially Modulate TGFb-Induced Inhibition of Embryonic Lung Morphogenesis. Journal of Biological Chemistry 275: 23992-23997 Shi W, Heisterkamp N, Groffen J, Zhao J, Warburton D, Kaartinen V (1999). TGF-b3 null mutation does not abrogate fetal lung maturation in vivo by glucocorticoids. American Journal of Physiology 277: L1205-L1213 Pfeffer LM, Mullersman JE, Pfeffer SR, Murti A, Shi W, Yang CH (1997). Stat3 as an adapter to couple phosphatidylinositol-3-kinase to the IFNAR1 chain of the type I IFN receptor. Science 276(5317):1418-1420 Yang CH, Shi W, Basu L, Murti A, Constantinescu SN, Blatt L, Croze E, Mullersman JE, Pfeffer LM (1996). Constantinescu, Lawrence Blatt, Ed Croze, Jerald E. Mullersman, Lawrence M. Pfeffer. Direct association of Stat3 with the IFNAR-1 chain of the human type I interferon receptor. Journal of Biological Chemistry 271(14):8057-8061 Shi W, Zhang CY, Wuang GQ, Wang ZY (1990). Studies on purification and characterization of pro-urokinase. Progress in Biochemistry and Biophysics 17(5):376-379 (Chinese). Shi W, Zhang CY (1990). The structure and characteristics of scuPA. Sheng Li Ke Xue Jin Zhan 21(4):314-7 Shi W, Zhang CY, Wuang GQ, Wang ZY (1990). Studies on synergism between pro-urokinase and tissue plasminogen activator or urokinase in clot lysis experiments in vitro. Journal of Chinese Hematology 11(10):509-511, (Chinese) Shi W, Zhang CY, Wuang GQ, Wang ZY (1989). Purification and partial characterization of single-chain urokinase-type plasminogen activator. Thrombosis & Haemostasis 62(1):1277 |
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Last Updated: 04/28/08
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