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    Dean Sheppard, MD

    TitleProfessor
    SchoolUCSF School of Medicine
    DepartmentMedicine
    Address1550 4th St., Mission Bay
    Phone415-514-4269

       Biography 
       Education and Training
      Institution Degree School or Department Year
      University of California, San FranciscoResidency School of Medicine
      SUNY, Stony BrookM.D.School of Medicine1975

       Overview 
       Overview
      Dean Sheppard received an AB (Social Studies) from Harvard College in 1972, and an MD from SUNY at Stony Brook in 1975. He trained in Internal Medicine at the University of Washington in Seattle and in Pulmonary Medicine at UCSF. He has been on the faculty of UCSF since 1980 and was appointed the founding director of the Lung Biology Research Center in 1986. He has been the Chief of the Division of Pulmonary, Critical Care, Allergy and Sleep since 2009. Dr. Sheppard is Professor of Medicine and a member of the Cell Biology, Biomedical Sciences, Immunology and Pharmaceutical Sciences and Pharmacogenomics graduate programs.

      Research Interests

      Dr. Sheppard’s research focuses on the molecular mechanisms underlying pulmonary (and other organ) fibrosis, asthma and acute lung injury. One aim of the research is to identify new therapeutic targets to ultimately improve the treatment of each of these common diseases. The work begins with basic investigation of how cells use members of the integrin family to detect, modify and respond to spatially restricted extracellular clues and how these responses contribute to the development of common lung diseases. Utilizing mice with global or conditional knockouts of four integrins, the epithelial-restricted integrin, avß6, and the widely expressed integrins a9ß1, avß5 and avß8, the lab has identified important roles for these integrins in models of each common lung disease and key steps upstream and downstream of the integrins that provide potential therapeutic targets.

      avß6 has two distinct functions: enhancement of cell proliferation, and activation of latent transforming growth factor beta (TGFß), that depend on distinct sequences in the ß6 cytoplasmic domain. We have shown that the latter function plays a central role in pulmonary and renal fibrosis, acute lung injury, protection from pulmonary emphysema, tumor invasion and in the airway hyperresponsiveness that follows chronic allergen challenge. Currently we are identifying pathways that regulate each of these responses. A humanized monoclonal antibody generated by immunizing our knockout mice is currently in clinical trials for treatment of pulmonary and renal fibrosis. We have also found that mice lacking all av integrins on myofibroblasts are protected from pulmonary, hepatic and renal fibrosis and are using this model to develop new approaches for treating a wide variety of fibrotic diseases.

      The avß8 integrin also activates TGFß. Mice we have generated lacking this integrin on dendritic cells develop auto-immunity and colitis, suggesting avß8-mediated TGFß activation on dendritic cells negatively regulates adaptive immunity. However, these mice are dramatically protected from pathology in a number of immune-mediated disease models, including a model of allergic asthma. We are currently characterizing the mechanisms underlying these effects, the mechanisms by which this process is regulated during the induction of adaptive immune responses, and the relevance of this pathway in various models of immune-mediated disease.

      a9ß1 is expressed by a wide variety of cells and recognizes at least 15 distinct ligands. a9ß1 is critical for cell migration, an effect that depends on unique sequences in the a9 cytoplasmic domain. As a9 ko mice are not viable, we have generated mice expressing a conditional null allele to better the role of this integrin in vivo. Mice lacking this integrin in airway smooth muscle cells develop spontaneous airway hyperresponsiveness, resembling asthma. We have used these mice and cells and tissues from their lungs to identify a completely novel pathway regulating airway smooth muscle contraction, and are currently working to develop specific inhibitors of pathway components in the hope of finding new treatments for asthma.

      avß5 is also widely expressed, but mice lacking this integrin are phenotypically normal. However, these mice are dramatically protected in multiple models of acute lung injury and septic shock. This phenotype is explained, at least in part, by a central role for this integrin in regulating reorganization of the actin cytoskeleton in activated endothelial cells. We are currently examining the mechanisms by which this integrin, and its close relative, avß3, exert opposing effects on actin organization, vascular permeability and tissue edema. We have also generated a potent blocking antibody to avß5 that we hope to develop for treatment of acute lung injury and septic shock.


       ORNG Applications 
       Websites
       Awarded Grants
       Global Health
       More Info

       Bibliographic 
       Publications
      Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
      List All   |   Timeline
      1. Erle DJ, Sheppard D. The cell biology of asthma. J Cell Biol. 2014 Jun 9; 205(5):621-31.
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      2. Ito K, Morimoto J, Kihara A, Matsui Y, Kurotaki D, Kanayama M, Simmons S, Ishii M, Sheppard D, Takaoka A, Uede T. Integrin a9 on lymphatic endothelial cells regulates lymphocyte egress. Proc Natl Acad Sci U S A. 2014 Feb 25; 111(8):3080-5.
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      3. Madala SK, Korfhagen TR, Schmidt S, Davidson C, Edukulla R, Ikegami M, Violette SM, Weinreb PH, Sheppard D, Hardie WD. Inhibition of the avß6 integrin leads to limited alteration of TGF-a-induced pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 2014 Apr; 306(8):L726-35.
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      4. Blackwell TS, Tager AM, Borok Z, Moore BB, Schwartz DA, Anstrom KJ, Bar-Joseph Z, Bitterman P, Blackburn MR, Bradford W, Brown KK, Chapman HA, Collard HR, Cosgrove GP, Deterding R, Doyle R, Flaherty KR, Garcia CK, Hagood JS, Henke CA, Herzog E, Hogaboam CM, Horowitz JC, King TE, Loyd JE, Lawson WE, Marsh CB, Noble PW, Noth I, Sheppard D, Olsson J, Ortiz LA, O'Riordan TG, Oury TD, Raghu G, Roman J, Sime PJ, Sisson TH, Tschumperlin D, Violette SM, Weaver TE, Wells RG, White ES, Kaminski N, Martinez FJ, Wynn TA, Thannickal VJ, Eu JP. Future Directions in Idiopathic Pulmonary Fibrosis Research. An NHLBI Workshop Report. Am J Respir Crit Care Med. 2014 Jan 15; 189(2):214-22.
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      5. Travis MA, Sheppard D. TGF-ß Activation and Function in Immunity. Annu Rev Immunol. 2014 Mar 21; 32:51-82.
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      6. Henderson NC, Arnold TD, Katamura Y, Giacomini MM, Rodriguez JD, McCarty JH, Pellicoro A, Raschperger E, Betsholtz C, Ruminski PG, Griggs DW, Prinsen MJ, Maher JJ, Iredale JP, Lacy-Hulbert A, Adams RH, Sheppard D. Targeting of av integrin identifies a core molecular pathway that regulates fibrosis in several organs. Nat Med. 2013 Dec; 19(12):1617-24.
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      7. Goh YP, Henderson NC, Heredia JE, Red Eagle A, Odegaard JI, Lehwald N, Nguyen KD, Sheppard D, Mukundan L, Locksley RM, Chawla A. Eosinophils secrete IL-4 to facilitate liver regeneration. Proc Natl Acad Sci U S A. 2013 Jun 11; 110(24):9914-9.
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      8. Katsumoto TR, Kudo M, Chen C, Sundaram A, Callahan EC, Zhu JW, Lin J, Rosen CE, Manz BN, Lee JW, Matthay MA, Huang X, Sheppard D, Weiss A. The phosphatase CD148 promotes airway hyperresponsiveness through SRC family kinases. J Clin Invest. 2013 May 1; 123(5):2037-48.
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      9. Sheppard D. ROCKing pulmonary fibrosis. J Clin Invest. 2013 Mar 1; 123(3):1005-6.
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      10. Su G, Atakilit A, Li JT, Wu N, Luong J, Chen R, Bhattacharya M, Sheppard D. Effective treatment of mouse sepsis with an inhibitory antibody targeting integrin avß5. Crit Care Med. 2013 Feb; 41(2):546-53.
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      11. Friedman SL, Sheppard D, Duffield JS, Violette S. Therapy for fibrotic diseases: nearing the starting line. Sci Transl Med. 2013 Jan 9; 5(167):167sr1.
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      12. Freimuth J, Clermont FF, Huang X, DeSapio A, Tokuyasu TA, Sheppard D, Akhurst RJ. Epistatic interactions between Tgfb1 and genetic loci, Tgfbm2 and Tgfbm3, determine susceptibility to an asthmatic stimulus. Proc Natl Acad Sci U S A. 2012 Oct 30; 109(44):18042-7.
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      13. Henderson NC, Sheppard D. Integrin-mediated regulation of TGFß in fibrosis. Biochim Biophys Acta. 2013 Jul; 1832(7):891-6.
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      14. Huang F, Zhang H, Wu M, Yang H, Kudo M, Peters CJ, Woodruff PG, Solberg OD, Donne ML, Huang X, Sheppard D, Fahy JV, Wolters PJ, Hogan BL, Finkbeiner WE, Li M, Jan YN, Jan LY, Rock JR. Calcium-activated chloride channel TMEM16A modulates mucin secretion and airway smooth muscle contraction. Proc Natl Acad Sci U S A. 2012 Oct 2; 109(40):16354-9.
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      15. Chen C, Kudo M, Rutaganira F, Takano H, Lee C, Atakilit A, Robinett KS, Uede T, Wolters PJ, Shokat KM, Huang X, Sheppard D. Integrin a9ß1 in airway smooth muscle suppresses exaggerated airway narrowing. J Clin Invest. 2012 Aug 1; 122(8):2916-27.
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      16. Sheppard D. Modulation of acute lung injury by integrins. Proc Am Thorac Soc. 2012 Jul; 9(3):126-9.
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      17. Thornton EE, Looney MR, Bose O, Sen D, Sheppard D, Locksley R, Huang X, Krummel MF. Spatiotemporally separated antigen uptake by alveolar dendritic cells and airway presentation to T cells in the lung. J Exp Med. 2012 Jun 4; 209(6):1183-99.
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      18. Bhattacharya M, Su G, Su X, Oses-Prieto JA, Li JT, Huang X, Hernandez H, Atakilit A, Burlingame AL, Matthay MA, Sheppard D. IQGAP1 is necessary for pulmonary vascular barrier protection in murine acute lung injury and pneumonia. Am J Physiol Lung Cell Mol Physiol. 2012 Jul 1; 303(1):L12-9.
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      19. Kudo M, Melton AC, Chen C, Engler MB, Huang KE, Ren X, Wang Y, Bernstein X, Li JT, Atabai K, Huang X, Sheppard D. IL-17A produced by aß T cells drives airway hyper-responsiveness in mice and enhances mouse and human airway smooth muscle contraction. Nat Med. 2012 Apr; 18(4):547-54.
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      20. Doherty TA, Khorram N, Sugimoto K, Sheppard D, Rosenthal P, Cho JY, Pham A, Miller M, Croft M, Broide DH. Alternaria induces STAT6-dependent acute airway eosinophilia and epithelial FIZZ1 expression that promotes airway fibrosis and epithelial thickness. J Immunol. 2012 Mar 15; 188(6):2622-9.
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      21. Giacomini MM, Travis MA, Kudo M, Sheppard D. Epithelial cells utilize cortical actin/myosin to activate latent TGF-ß through integrin a(v)ß(6)-dependent physical force. Exp Cell Res. 2012 Apr 1; 318(6):716-22.
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      22. Sugimoto K, Kudo M, Sundaram A, Ren X, Huang K, Bernstein X, Wang Y, Raymond WW, Erle DJ, Abrink M, Caughey GH, Huang X, Sheppard D. The avß6 integrin modulates airway hyperresponsiveness in mice by regulating intraepithelial mast cells. J Clin Invest. 2012 Feb 1; 122(2):748-58.
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      23. Su G, Atakilit A, Li JT, Wu N, Bhattacharya M, Zhu J, Shieh JE, Li E, Chen R, Sun S, Su CP, Sheppard D. Absence of integrin avß3 enhances vascular leak in mice by inhibiting endothelial cortical actin formation. Am J Respir Crit Care Med. 2012 Jan 1; 185(1):58-66.
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      24. Munger JS, Sheppard D. Cross talk among TGF-ß signaling pathways, integrins, and the extracellular matrix. Cold Spring Harb Perspect Biol. 2011 Nov; 3(11):a005017.
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      25. Tatler AL, John AE, Jolly L, Habgood A, Porte J, Brightling C, Knox AJ, Pang L, Sheppard D, Huang X, Jenkins G. Integrin avß5-mediated TGF-ß activation by airway smooth muscle cells in asthma. J Immunol. 2011 Dec 1; 187(11):6094-107.
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      26. Katsumoto TR, Violette SM, Sheppard D. Blocking TGFß via Inhibition of the avß6 Integrin: A Possible Therapy for Systemic Sclerosis Interstitial Lung Disease. Int J Rheumatol. 2011; 2011:208219.
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      27. Sheppard D. Aspen Lung Conference 2010: systems biology of lung diseases--progress in the omics era. Proc Am Thorac Soc. 2011 May; 8(2):199-202.
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      28. Kon S, Atakilit A, Sheppard D. Short form of a9 promotes a9ß1 integrin-dependent cell adhesion by modulating the function of the full-length a9 subunit. Exp Cell Res. 2011 Jul 15; 317(12):1774-84.
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      29. Nishimichi N, Hayashita-Kinoh H, Chen C, Matsuda H, Sheppard D, Yokosaki Y. Osteopontin undergoes polymerization in vivo and gains chemotactic activity for neutrophils mediated by integrin alpha9beta1. J Biol Chem. 2011 Apr 1; 286(13):11170-8.
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      30. Spassov DS, Wong CH, Sergina N, Ahuja D, Fried M, Sheppard D, Moasser MM. Phosphorylation of Trask by Src kinases inhibits integrin clustering and functions in exclusion with focal adhesion signaling. Mol Cell Biol. 2011 Feb; 31(4):766-82.
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      31. Melton AC, Bailey-Bucktrout SL, Travis MA, Fife BT, Bluestone JA, Sheppard D. Expression of avß8 integrin on dendritic cells regulates Th17 cell development and experimental autoimmune encephalomyelitis in mice. J Clin Invest. 2010 Dec; 120(12):4436-44.
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      32. Atabai K, Jame S, Azhar N, Kuo A, Lam M, McKleroy W, Dehart G, Rahman S, Xia DD, Melton AC, Wolters P, Emson CL, Turner SM, Werb Z, Sheppard D. Mfge8 diminishes the severity of tissue fibrosis in mice by binding and targeting collagen for uptake by macrophages. J Clin Invest. 2009 Dec; 119(12):3713-22.
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      33. Hogmalm A, Sheppard D, Lappalainen U, Bry K. beta6 Integrin subunit deficiency alleviates lung injury in a mouse model of bronchopulmonary dysplasia. Am J Respir Cell Mol Biol. 2010 Jul; 43(1):88-98.
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      34. Bazigou E, Xie S, Chen C, Weston A, Miura N, Sorokin L, Adams R, Muro AF, Sheppard D, Makinen T. Integrin-alpha9 is required for fibronectin matrix assembly during lymphatic valve morphogenesis. Dev Cell. 2009 Aug; 17(2):175-86.
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      35. Seibold MA, Reese TA, Choudhry S, Salam MT, Beckman K, Eng C, Atakilit A, Meade K, Lenoir M, Watson HG, Thyne S, Kumar R, Weiss KB, Grammer LC, Avila P, Schleimer RP, Fahy JV, Rodriguez-Santana J, Rodriguez-Cintron W, Boot RG, Sheppard D, Gilliland FD, Locksley RM, Burchard EG. Differential enzymatic activity of common haplotypic versions of the human acidic Mammalian chitinase protein. J Biol Chem. 2009 Jul 17; 284(29):19650-8.
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      36. Grassinger J, Haylock DN, Storan MJ, Haines GO, Williams B, Whitty GA, Vinson AR, Be CL, Li S, Sørensen ES, Tam PP, Denhardt DT, Sheppard D, Choong PF, Nilsson SK. Thrombin-cleaved osteopontin regulates hemopoietic stem and progenitor cell functions through interactions with alpha9beta1 and alpha4beta1 integrins. Blood. 2009 Jul 2; 114(1):49-59.
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      37. Xu MY, Porte J, Knox AJ, Weinreb PH, Maher TM, Violette SM, McAnulty RJ, Sheppard D, Jenkins G. Lysophosphatidic acid induces alphavbeta6 integrin-mediated TGF-beta activation via the LPA2 receptor and the small G protein G alpha(q). Am J Pathol. 2009 Apr; 174(4):1264-79.
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      38. Singh P, Chen C, Pal-Ghosh S, Stepp MA, Sheppard D, Van De Water L. Loss of integrin alpha9beta1 results in defects in proliferation, causing poor re-epithelialization during cutaneous wound healing. J Invest Dermatol. 2009 Jan; 129(1):217-28.
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      39. deHart GW, Jin T, McCloskey DE, Pegg AE, Sheppard D. The alpha9beta1 integrin enhances cell migration by polyamine-mediated modulation of an inward-rectifier potassium channel. Proc Natl Acad Sci U S A. 2008 May 20; 105(20):7188-93.
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      40. Sheppard D. Dust mites' dirty dealings with dendritic cells. Nat Med. 2008 May; 14(5):487-8.
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      41. Tabata T, Kawakatsu H, Maidji E, Sakai T, Sakai K, Fang-Hoover J, Aiba M, Sheppard D, Pereira L. Induction of an epithelial integrin alphavbeta6 in human cytomegalovirus-infected endothelial cells leads to activation of transforming growth factor-beta1 and increased collagen production. Am J Pathol. 2008 Apr; 172(4):1127-40.
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      42. Ganter MT, Roux J, Miyazawa B, Howard M, Frank JA, Su G, Sheppard D, Violette SM, Weinreb PH, Horan GS, Matthay MA, Pittet JF. Interleukin-1beta causes acute lung injury via alphavbeta5 and alphavbeta6 integrin-dependent mechanisms. Circ Res. 2008 Apr 11; 102(7):804-12.
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      43. Muro AF, Moretti FA, Moore BB, Yan M, Atrasz RG, Wilke CA, Flaherty KR, Martinez FJ, Tsui JL, Sheppard D, Baralle FE, Toews GB, White ES. An essential role for fibronectin extra type III domain A in pulmonary fibrosis. Am J Respir Crit Care Med. 2008 Mar 15; 177(6):638-45.
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      44. Araya J, Cambier S, Markovics JA, Wolters P, Jablons D, Hill A, Finkbeiner W, Jones K, Broaddus VC, Sheppard D, Barzcak A, Xiao Y, Erle DJ, Nishimura SL. Squamous metaplasia amplifies pathologic epithelial-mesenchymal interactions in COPD patients. J Clin Invest. 2007 Nov; 117(11):3551-62.
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      45. Horan GS, Wood S, Ona V, Li DJ, Lukashev ME, Weinreb PH, Simon KJ, Hahm K, Allaire NE, Rinaldi NJ, Goyal J, Feghali-Bostwick CA, Matteson EL, O'Hara C, Lafyatis R, Davis GS, Huang X, Sheppard D, Violette SM. Partial inhibition of integrin alpha(v)beta6 prevents pulmonary fibrosis without exacerbating inflammation. Am J Respir Crit Care Med. 2008 Jan 1; 177(1):56-65.
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      46. Travis MA, Reizis B, Melton AC, Masteller E, Tang Q, Proctor JM, Wang Y, Bernstein X, Huang X, Reichardt LF, Bluestone JA, Sheppard D. Loss of integrin alpha(v)beta8 on dendritic cells causes autoimmunity and colitis in mice. Nature. 2007 Sep 20; 449(7160):361-5.
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      47. Koth LL, Alex B, Hawgood S, Nead MA, Sheppard D, Erle DJ, Morris DG. Integrin beta6 mediates phospholipid and collectin homeostasis by activation of latent TGF-beta1. Am J Respir Cell Mol Biol. 2007 Dec; 37(6):651-9.
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      48. Nandrot EF, Anand M, Almeida D, Atabai K, Sheppard D, Finnemann SC. Essential role for MFG-E8 as ligand for alphavbeta5 integrin in diurnal retinal phagocytosis. Proc Natl Acad Sci U S A. 2007 Jul 17; 104(29):12005-10.
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      49. Raj JU, Aliferis C, Caprioli RM, Cowley AW, Davies PF, Duncan MW, Erle DJ, Erzurum SC, Finn PW, Ischiropoulos H, Kaminski N, Kleeberger SR, Leikauf GD, Loyd JE, Martin TR, Matalon S, Moore JH, Quackenbush J, Sabo-Attwood T, Shapiro SD, Schnitzer JE, Schwartz DA, Schwiebert LM, Sheppard D, Ware LB, Weiss ST, Whitsett JA, Wurfel MM, Matthay MA. Genomics and proteomics of lung disease: conference summary. Am J Physiol Lung Cell Mol Physiol. 2007 Jul; 293(1):L45-51.
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      50. Vlahakis NE, Young BA, Atakilit A, Hawkridge AE, Issaka RB, Boudreau N, Sheppard D. Integrin alpha9beta1 directly binds to vascular endothelial growth factor (VEGF)-A and contributes to VEGF-A-induced angiogenesis. J Biol Chem. 2007 May 18; 282(20):15187-96.
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      51. Atabai K, Sheppard D, Werb Z. Roles of the innate immune system in mammary gland remodeling during involution. J Mammary Gland Biol Neoplasia. 2007 Mar; 12(1):37-45.
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      52. Chen C, Sheppard D. Identification and molecular characterization of multiple phenotypes in integrin knockout mice. Methods Enzymol. 2007; 426:291-305.
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      53. Hahm K, Lukashev ME, Luo Y, Yang WJ, Dolinski BM, Weinreb PH, Simon KJ, Chun Wang L, Leone DR, Lobb RR, McCrann DJ, Allaire NE, Horan GS, Fogo A, Kalluri R, Shield CF, Sheppard D, Gardner HA, Violette SM. Alphav beta6 integrin regulates renal fibrosis and inflammation in Alport mouse. Am J Pathol. 2007 Jan; 170(1):110-25.
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      54. Morris DG, Sheppard D. Pulmonary emphysema: when more is less. Physiology (Bethesda). 2006 Dec; 21:396-403.
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      55. Chen C, Huang X, Atakilit A, Zhu QS, Corey SJ, Sheppard D. The Integrin alpha9beta1 contributes to granulopoiesis by enhancing granulocyte colony-stimulating factor receptor signaling. Immunity. 2006 Dec; 25(6):895-906.
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      56. Su G, Hodnett M, Wu N, Atakilit A, Kosinski C, Godzich M, Huang XZ, Kim JK, Frank JA, Matthay MA, Sheppard D, Pittet JF. Integrin alphavbeta5 regulates lung vascular permeability and pulmonary endothelial barrier function. Am J Respir Cell Mol Biol. 2007 Mar; 36(3):377-86.
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      57. Rao H, Lu G, Kajiya H, Garcia-Palacios V, Kurihara N, Anderson J, Patrene K, Sheppard D, Blair HC, Windle JJ, Choi SJ, Roodman GD. Alpha9beta1: a novel osteoclast integrin that regulates osteoclast formation and function. J Bone Miner Res. 2006 Oct; 21(10):1657-65.
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      58. Chen C, Huang X, Sheppard D. ADAM33 is not essential for growth and development and does not modulate allergic asthma in mice. Mol Cell Biol. 2006 Sep; 26(18):6950-6.
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      59. Kim KK, Kugler MC, Wolters PJ, Robillard L, Galvez MG, Brumwell AN, Sheppard D, Chapman HA. Alveolar epithelial cell mesenchymal transition develops in vivo during pulmonary fibrosis and is regulated by the extracellular matrix. Proc Natl Acad Sci U S A. 2006 Aug 29; 103(35):13180-5.
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      60. Sheppard D. Transforming growth factor beta: a central modulator of pulmonary and airway inflammation and fibrosis. Proc Am Thorac Soc. 2006 Jul; 3(5):413-7.
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      61. Jenkins RG, Su X, Su G, Scotton CJ, Camerer E, Laurent GJ, Davis GE, Chambers RC, Matthay MA, Sheppard D. Ligation of protease-activated receptor 1 enhances alpha(v)beta6 integrin-dependent TGF-beta activation and promotes acute lung injury. J Clin Invest. 2006 Jun; 116(6):1606-14.
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      62. Neurohr C, Nishimura SL, Sheppard D. Activation of transforming growth factor-beta by the integrin alphavbeta8 delays epithelial wound closure. Am J Respir Cell Mol Biol. 2006 Aug; 35(2):252-9.
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      63. Choudhry S, Coyle NE, Tang H, Salari K, Lind D, Clark SL, Tsai HJ, Naqvi M, Phong A, Ung N, Matallana H, Avila PC, Casal J, Torres A, Nazario S, Castro R, Battle NC, Perez-Stable EJ, Kwok PY, Sheppard D, Shriver MD, Rodriguez-Cintron W, Risch N, Ziv E, Burchard EG. Population stratification confounds genetic association studies among Latinos. Hum Genet. 2006 Jan; 118(5):652-64.
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      64. Atabai K, Fernandez R, Huang X, Ueki I, Kline A, Li Y, Sadatmansoori S, Smith-Steinhart C, Zhu W, Pytela R, Werb Z, Sheppard D. Mfge8 is critical for mammary gland remodeling during involution. Mol Biol Cell. 2005 Dec; 16(12):5528-37.
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      65. Sheppard D. Integrin-mediated activation of latent transforming growth factor beta. Cancer Metastasis Rev. 2005 Sep; 24(3):395-402.
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      66. Salari K, Choudhry S, Tang H, Naqvi M, Lind D, Avila PC, Coyle NE, Ung N, Nazario S, Casal J, Torres-Palacios A, Clark S, Phong A, Gomez I, Matallana H, Pérez-Stable EJ, Shriver MD, Kwok PY, Sheppard D, Rodriguez-Cintron W, Risch NJ, Burchard EG, Ziv E. Genetic admixture and asthma-related phenotypes in Mexican American and Puerto Rican asthmatics. Genet Epidemiol. 2005 Jul; 29(1):76-86.
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      67. Ludlow A, Yee KO, Lipman R, Bronson R, Weinreb P, Huang X, Sheppard D, Lawler J. Characterization of integrin beta6 and thrombospondin-1 double-null mice. J Cell Mol Med. 2005 Apr-Jun; 9(2):421-37.
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      68. Bridges LC, Sheppard D, Bowditch RD. ADAM disintegrin-like domain recognition by the lymphocyte integrins alpha4beta1 and alpha4beta7. Biochem J. 2005 Apr 1; 387(Pt 1):101-8.
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      69. Roux J, Kawakatsu H, Gartland B, Pespeni M, Sheppard D, Matthay MA, Canessa CM, Pittet JF. Interleukin-1beta decreases expression of the epithelial sodium channel alpha-subunit in alveolar epithelial cells via a p38 MAPK-dependent signaling pathway. J Biol Chem. 2005 May 13; 280(19):18579-89.
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      70. Bates RC, Bellovin DI, Brown C, Maynard E, Wu B, Kawakatsu H, Sheppard D, Oettgen P, Mercurio AM. Transcriptional activation of integrin beta6 during the epithelial-mesenchymal transition defines a novel prognostic indicator of aggressive colon carcinoma. J Clin Invest. 2005 Feb; 115(2):339-47.
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      71. Nandrot EF, Kim Y, Brodie SE, Huang X, Sheppard D, Finnemann SC. Loss of synchronized retinal phagocytosis and age-related blindness in mice lacking alphavbeta5 integrin. J Exp Med. 2004 Dec 20; 200(12):1539-45.
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      72. Vlahakis NE, Young BA, Atakilit A, Sheppard D. The lymphangiogenic vascular endothelial growth factors VEGF-C and -D are ligands for the integrin alpha9beta1. J Biol Chem. 2005 Feb 11; 280(6):4544-52.
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      73. Choudhry S, Ung N, Avila PC, Ziv E, Nazario S, Casal J, Torres A, Gorman JD, Salari K, Rodriguez-Santana JR, Toscano M, Sylvia JS, Alioto M, Castro RA, Salazar M, Gomez I, Fagan JK, Salas J, Clark S, Lilly C, Matallana H, Selman M, Chapela R, Sheppard D, Weiss ST, Ford JG, Boushey HA, Drazen JM, Rodriguez-Cintron W, Silverman EK, Burchard EG. Pharmacogenetic differences in response to albuterol between Puerto Ricans and Mexicans with asthma. Am J Respir Crit Care Med. 2005 Mar 15; 171(6):563-70.
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      74. Lane NE, Yao W, Nakamura MC, Humphrey MB, Kimmel D, Huang X, Sheppard D, Ross FP, Teitelbaum SL. Mice lacking the integrin beta5 subunit have accelerated osteoclast maturation and increased activity in the estrogen-deficient state. J Bone Miner Res. 2005 Jan; 20(1):58-66.
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      75. Sheppard D. Fishing in the bloodstream: insights into the mechanisms of pulmonary hypertension? Am J Respir Crit Care Med. 2004 Oct 15; 170(8):827-8.
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      76. Chen C, Young BA, Coleman CS, Pegg AE, Sheppard D. Spermidine/spermine N1-acetyltransferase specifically binds to the integrin alpha9 subunit cytoplasmic domain and enhances cell migration. J Cell Biol. 2004 Oct 11; 167(1):161-70.
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      77. Sheppard D. Roles of alphav integrins in vascular biology and pulmonary pathology. Curr Opin Cell Biol. 2004 Oct; 16(5):552-7.
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      78. Williams CH, Kajander T, Hyypiä T, Jackson T, Sheppard D, Stanway G. Integrin alpha v beta 6 is an RGD-dependent receptor for coxsackievirus A9. J Virol. 2004 Jul; 78(13):6967-73.
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      79. Bazan-Socha S, Kisiel DG, Young B, Theakston RD, Calvete JJ, Sheppard D, Marcinkiewicz C. Structural requirements of MLD-containing disintegrins for functional interaction with alpha 4 beta 1 and alpha 9 beta1 integrins. Biochemistry. 2004 Feb 17; 43(6):1639-47.
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      80. Weinreb PH, Simon KJ, Rayhorn P, Yang WJ, Leone DR, Dolinski BM, Pearse BR, Yokota Y, Kawakatsu H, Atakilit A, Sheppard D, Violette SM. Function-blocking integrin alphavbeta6 monoclonal antibodies: distinct ligand-mimetic and nonligand-mimetic classes. J Biol Chem. 2004 Apr 23; 279(17):17875-87.
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      81. Burchard EG, Avila PC, Nazario S, Casal J, Torres A, Rodriguez-Santana JR, Toscano M, Sylvia JS, Alioto M, Salazar M, Gomez I, Fagan JK, Salas J, Lilly C, Matallana H, Ziv E, Castro R, Selman M, Chapela R, Sheppard D, Weiss ST, Ford JG, Boushey HA, Rodriguez-Cintron W, Drazen JM, Silverman EK. Lower bronchodilator responsiveness in Puerto Rican than in Mexican subjects with asthma. Am J Respir Crit Care Med. 2004 Feb 1; 169(3):386-92.
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      82. Tomczuk M, Takahashi Y, Huang J, Murase S, Mistretta M, Klaffky E, Sutherland A, Bolling L, Coonrod S, Marcinkiewicz C, Sheppard D, Stepp MA, White JM. Role of multiple beta1 integrins in cell adhesion to the disintegrin domains of ADAMs 2 and 3. Exp Cell Res. 2003 Oct 15; 290(1):68-81.
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      83. Ma LJ, Yang H, Gaspert A, Carlesso G, Barty MM, Davidson JM, Sheppard D, Fogo AB. Transforming growth factor-beta-dependent and -independent pathways of induction of tubulointerstitial fibrosis in beta6(-/-) mice. Am J Pathol. 2003 Oct; 163(4):1261-73.
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      84. Wu W, Samet JM, Silbajoris R, Dailey LA, Sheppard D, Bromberg PA, Graves LM. Heparin-binding epidermal growth factor cleavage mediates zinc-induced epidermal growth factor receptor phosphorylation. Am J Respir Cell Mol Biol. 2004 Apr; 30(4):540-7.
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      85. Lind DL, Choudhry S, Ung N, Ziv E, Avila PC, Salari K, Ha C, Lovins EG, Coyle NE, Nazario S, Casal J, Torres A, Rodriguez-Santana JR, Matallana H, Lilly CM, Salas J, Selman M, Boushey HA, Weiss ST, Chapela R, Ford JG, Rodriguez-Cintron W, Silverman EK, Sheppard D, Kwok PY, González Burchard E. ADAM33 is not associated with asthma in Puerto Rican or Mexican populations. Am J Respir Crit Care Med. 2003 Dec 1; 168(11):1312-6.
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      86. Frank J, Roux J, Kawakatsu H, Su G, Dagenais A, Berthiaume Y, Howard M, Canessa CM, Fang X, Sheppard D, Matthay MA, Pittet JF. Transforming growth factor-beta1 decreases expression of the epithelial sodium channel alphaENaC and alveolar epithelial vectorial sodium and fluid transport via an ERK1/2-dependent mechanism. J Biol Chem. 2003 Nov 7; 278(45):43939-50.
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      87. Sheppard D. Functions of pulmonary epithelial integrins: from development to disease. Physiol Rev. 2003 Jul; 83(3):673-86.
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      88. Burchard EG, Ziv E, Coyle N, Gomez SL, Tang H, Karter AJ, Mountain JL, Pérez-Stable EJ, Sheppard D, Risch N. The importance of race and ethnic background in biomedical research and clinical practice. N Engl J Med. 2003 Mar 20; 348(12):1170-5.
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      89. Morris DG, Huang X, Kaminski N, Wang Y, Shapiro SD, Dolganov G, Glick A, Sheppard D. Loss of integrin alpha(v)beta6-mediated TGF-beta activation causes Mmp12-dependent emphysema. Nature. 2003 Mar 13; 422(6928):169-73.
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      90. Sheppard D. Endothelial integrins and angiogenesis: not so simple anymore. J Clin Invest. 2002 Oct; 110(7):913-4.
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      91. Knight PA, Wright SH, Brown JK, Huang X, Sheppard D, Miller HR. Enteric expression of the integrin alpha(v)beta(6) is essential for nematode-induced mucosal mast cell hyperplasia and expression of the granule chymase, mouse mast cell protease-1. Am J Pathol. 2002 Sep; 161(3):771-9.
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      92. Crystal RG, Bitterman PB, Mossman B, Schwarz MI, Sheppard D, Almasy L, Chapman HA, Friedman SL, King TE, Leinwand LA, Liotta L, Martin GR, Schwartz DA, Schultz GS, Wagner CR, Musson RA. Future research directions in idiopathic pulmonary fibrosis: summary of a National Heart, Lung, and Blood Institute working group. Am J Respir Crit Care Med. 2002 Jul 15; 166(2):236-46.
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      93. Kuperman DA, Huang X, Koth LL, Chang GH, Dolganov GM, Zhu Z, Elias JA, Sheppard D, Erle DJ. Direct effects of interleukin-13 on epithelial cells cause airway hyperreactivity and mucus overproduction in asthma. Nat Med. 2002 Aug; 8(8):885-9.
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      94. Zuo F, Kaminski N, Eugui E, Allard J, Yakhini Z, Ben-Dor A, Lollini L, Morris D, Kim Y, DeLustro B, Sheppard D, Pardo A, Selman M, Heller RA. Gene expression analysis reveals matrilysin as a key regulator of pulmonary fibrosis in mice and humans. Proc Natl Acad Sci U S A. 2002 Apr 30; 99(9):6292-7.
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      95. Mu D, Cambier S, Fjellbirkeland L, Baron JL, Munger JS, Kawakatsu H, Sheppard D, Broaddus VC, Nishimura SL. The integrin alpha(v)beta8 mediates epithelial homeostasis through MT1-MMP-dependent activation of TGF-beta1. J Cell Biol. 2002 Apr 29; 157(3):493-507.
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      96. Eliceiri BP, Puente XS, Hood JD, Stupack DG, Schlaepfer DD, Huang XZ, Sheppard D, Cheresh DA. Src-mediated coupling of focal adhesion kinase to integrin alpha(v)beta5 in vascular endothelial growth factor signaling. J Cell Biol. 2002 Apr 1; 157(1):149-60.
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      97. Sheppard D. Killed by leukocytes that don't know when to leave. Nat Immunol. 2002 Apr; 3(4):337-8.
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      98. Eto K, Huet C, Tarui T, Kupriyanov S, Liu HZ, Puzon-McLaughlin W, Zhang XP, Sheppard D, Engvall E, Takada Y. Functional classification of ADAMs based on a conserved motif for binding to integrin alpha 9beta 1: implications for sperm-egg binding and other cell interactions. J Biol Chem. 2002 May 17; 277(20):17804-10.
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      99. Sheppard D. Roger S. Mitchell lecture. Uses of expression microarrays in studies of pulmonary fibrosis, asthma, acute lung injury, and emphysema. Chest. 2002 Mar; 121(3 Suppl):21S-25S.
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      100. Kaminski N, Zuo F, Cojocaro G, Yakhini Z, Ben-Dor A, Morris D, Sheppard D, Pardo A, Selman M, Heller RA. Use of oligonucleotide microarrays to analyze gene expression patterns in pulmonary fibrosis reveals distinct patterns of gene expression in mice and humans. Chest. 2002 Mar; 121(3 Suppl):31S-32S.
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      101. Liao YF, Gotwals PJ, Koteliansky VE, Sheppard D, Van De Water L. The EIIIA segment of fibronectin is a ligand for integrins alpha 9beta 1 and alpha 4beta 1 providing a novel mechanism for regulating cell adhesion by alternative splicing. J Biol Chem. 2002 Apr 26; 277(17):14467-74.
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      102. Jackson T, Mould AP, Sheppard D, King AM. Integrin alphavbeta1 is a receptor for foot-and-mouth disease virus. J Virol. 2002 Feb; 76(3):935-41.
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      103. Reynolds LE, Wyder L, Lively JC, Taverna D, Robinson SD, Huang X, Sheppard D, Hynes RO, Hodivala-Dilke KM. Enhanced pathological angiogenesis in mice lacking beta3 integrin or beta3 and beta5 integrins. Nat Med. 2002 Jan; 8(1):27-34.
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      104. Ljubimov AV, Saghizadeh M, Pytela R, Sheppard D, Kenney MC. Increased expression of tenascin-C-binding epithelial integrins in human bullous keratopathy corneas. J Histochem Cytochem. 2001 Nov; 49(11):1341-50.
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      105. Young BA, Taooka Y, Liu S, Askins KJ, Yokosaki Y, Thomas SM, Sheppard D. The cytoplasmic domain of the integrin alpha9 subunit requires the adaptor protein paxillin to inhibit cell spreading but promotes cell migration in a paxillin-independent manner. Mol Biol Cell. 2001 Oct; 12(10):3214-25.
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      106. Lee JH, Kaminski N, Dolganov G, Grunig G, Koth L, Solomon C, Erle DJ, Sheppard D. Interleukin-13 induces dramatically different transcriptional programs in three human airway cell types. Am J Respir Cell Mol Biol. 2001 Oct; 25(4):474-85.
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      107. Thomas GJ, Lewis MP, Whawell SA, Russell A, Sheppard D, Hart IR, Speight PM, Marshall JF. Expression of the alphavbeta6 integrin promotes migration and invasion in squamous carcinoma cells. J Invest Dermatol. 2001 Jul; 117(1):67-73.
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      108. Sheppard D. Integrin-mediated activation of transforming growth factor-beta(1) in pulmonary fibrosis. Chest. 2001 Jul; 120(1 Suppl):49S-53S.
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      109. Sheppard D. Pulmonary fibrosis: a cellular overreaction or a failure of communication? J Clin Invest. 2001 Jun; 107(12):1501-2.
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      110. Pittet JF, Griffiths MJ, Geiser T, Kaminski N, Dalton SL, Huang X, Brown LA, Gotwals PJ, Koteliansky VE, Matthay MA, Sheppard D. TGF-beta is a critical mediator of acute lung injury. J Clin Invest. 2001 Jun; 107(12):1537-44.
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      111. Miller LC, Blakemore W, Sheppard D, Atakilit A, King AM, Jackson T. Role of the cytoplasmic domain of the beta-subunit of integrin alpha(v)beta6 in infection by foot-and-mouth disease virus. J Virol. 2001 May; 75(9):4158-64.
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      112. Miller LA, Barnett NL, Sheppard D, Hyde DM. Expression of the beta6 integrin subunit is associated with sites of neutrophil influx in lung epithelium. J Histochem Cytochem. 2001 Jan; 49(1):41-8.
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      113. Eto K, Puzon-McLaughlin W, Sheppard D, Sehara-Fujisawa A, Zhang XP, Takada Y. RGD-independent binding of integrin alpha9beta1 to the ADAM-12 and -15 disintegrin domains mediates cell-cell interaction. J Biol Chem. 2000 Nov 10; 275(45):34922-30.
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      114. Marcinkiewicz C, Taooka Y, Yokosaki Y, Calvete JJ, Marcinkiewicz MM, Lobb RR, Niewiarowski S, Sheppard D. Inhibitory effects of MLDG-containing heterodimeric disintegrins reveal distinct structural requirements for interaction of the integrin alpha 9beta 1 with VCAM-1, tenascin-C, and osteopontin. J Biol Chem. 2000 Oct 13; 275(41):31930-7.
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      115. Davidson DJ, Kilanowski FM, Randell SH, Sheppard DN, Dorin JR. A primary culture model of differentiated murine tracheal epithelium. Am J Physiol Lung Cell Mol Physiol. 2000 Oct; 279(4):L766-78.
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      116. Albelda SM, Sheppard D. Functional genomics and expression profiling: be there or be square. Am J Respir Cell Mol Biol. 2000 Sep; 23(3):265-9.
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      117. Takahashi H, Isobe T, Horibe S, Takagi J, Yokosaki Y, Sheppard D, Saito Y. Tissue transglutaminase, coagulation factor XIII, and the pro-polypeptide of von Willebrand factor are all ligands for the integrins alpha 9beta 1 and alpha 4beta 1. J Biol Chem. 2000 Aug 4; 275(31):23589-95.
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      118. Huang XZ, Wu JF, Ferrando R, Lee JH, Wang YL, Farese RV, Sheppard D. Fatal bilateral chylothorax in mice lacking the integrin alpha9beta1. Mol Cell Biol. 2000 Jul; 20(14):5208-15.
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      119. Sheppard D. In vivo functions of integrins: lessons from null mutations in mice. Matrix Biol. 2000 Jul; 19(3):203-9.
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      120. Jackson T, Sheppard D, Denyer M, Blakemore W, King AM. The epithelial integrin alphavbeta6 is a receptor for foot-and-mouth disease virus. J Virol. 2000 Jun; 74(11):4949-56.
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      121. Yokasaki Y, Sheppard D. Mapping of the cryptic integrin-binding site in osteopontin suggests a new mechanism by which thrombin can regulate inflammation and tissue repair. Trends Cardiovasc Med. 2000 May; 10(4):155-9.
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      122. Lansdell KA, Cai Z, Kidd JF, Sheppard DN. Two mechanisms of genistein inhibition of cystic fibrosis transmembrane conductance regulator Cl- channels expressed in murine cell line. J Physiol. 2000 Apr 15; 524 Pt 2:317-30.
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      123. Kaminski N, Allard JD, Pittet JF, Zuo F, Griffiths MJ, Morris D, Huang X, Sheppard D, Heller RA. Global analysis of gene expression in pulmonary fibrosis reveals distinct programs regulating lung inflammation and fibrosis. Proc Natl Acad Sci U S A. 2000 Feb 15; 97(4):1778-83.
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      124. Huang X, Griffiths M, Wu J, Farese RV, Sheppard D. Normal development, wound healing, and adenovirus susceptibility in beta5-deficient mice. Mol Cell Biol. 2000 Feb; 20(3):755-9.
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      125. Yokosaki Y, Matsuura N, Sasaki T, Murakami I, Schneider H, Higashiyama S, Saitoh Y, Yamakido M, Taooka Y, Sheppard D. The integrin alpha(9)beta(1) binds to a novel recognition sequence (SVVYGLR) in the thrombin-cleaved amino-terminal fragment of osteopontin. J Biol Chem. 1999 Dec 17; 274(51):36328-34.
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      126. Milner R, Huang X, Wu J, Nishimura S, Pytela R, Sheppard D, ffrench-Constant C. Distinct roles for astrocyte alphavbeta5 and alphavbeta8 integrins in adhesion and migration. J Cell Sci. 1999 Dec; 112 ( Pt 23):4271-9.
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      127. Spirin KS, Ljubimov AV, Castellon R, Wiedoeft O, Marano M, Sheppard D, Kenney MC, Brown DJ. Analysis of gene expression in human bullous keratopathy corneas containing limiting amounts of RNA. Invest Ophthalmol Vis Sci. 1999 Dec; 40(13):3108-15.
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      128. Busse W, Elias J, Sheppard D, Banks-Schlegel S. Airway remodeling and repair. Am J Respir Crit Care Med. 1999 Sep; 160(3):1035-42.
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      129. Cai Z, Lansdell KA, Sheppard DN. Inhibition of heterologously expressed cystic fibrosis transmembrane conductance regulator Cl- channels by non-sulphonylurea hypoglycaemic agents. Br J Pharmacol. 1999 Sep; 128(1):108-18.
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      130. Roger P, Puchelle E, Bajolet-Laudinat O, Tournier JM, Debordeaux C, Plotkowski MC, Cohen JH, Sheppard D, de Bentzmann S. Fibronectin and alpha5beta1 integrin mediate binding of Pseudomonas aeruginosa to repairing airway epithelium. Eur Respir J. 1999 Jun; 13(6):1301-9.
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      131. Taooka Y, Chen J, Yednock T, Sheppard D. The integrin alpha9beta1 mediates adhesion to activated endothelial cells and transendothelial neutrophil migration through interaction with vascular cell adhesion molecule-1. J Cell Biol. 1999 Apr 19; 145(2):413-20.
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      132. Munger JS, Huang X, Kawakatsu H, Griffiths MJ, Dalton SL, Wu J, Pittet JF, Kaminski N, Garat C, Matthay MA, Rifkin DB, Sheppard D. The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell. 1999 Feb 5; 96(3):319-28.
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      133. Grünig G, Warnock M, Wakil AE, Venkayya R, Brombacher F, Rennick DM, Sheppard D, Mohrs M, Donaldson DD, Locksley RM, Corry DB. Requirement for IL-13 independently of IL-4 in experimental asthma. Science. 1998 Dec 18; 282(5397):2261-3.
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      134. Desloges N, Basora N, Perreault N, Bouatrouss Y, Sheppard D, Beaulieu JF. Regulated expression of the integrin alpha9beta1 in the epithelium of the developing human gut and in intestinal cell lines: relation with cell proliferation. J Cell Biochem. 1998 Dec 15; 71(4):536-45.
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      135. Huang X, Wu J, Zhu W, Pytela R, Sheppard D. Expression of the human integrin beta6 subunit in alveolar type II cells and bronchiolar epithelial cells reverses lung inflammation in beta6 knockout mice. Am J Respir Cell Mol Biol. 1998 Oct; 19(4):636-42.
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      136. Sheppard D. Airway epithelial integrins: why so many? Am J Respir Cell Mol Biol. 1998 Sep; 19(3):349-51.
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      137. Huang X, Wu J, Spong S, Sheppard D. The integrin alphavbeta6 is critical for keratinocyte migration on both its known ligand, fibronectin, and on vitronectin. J Cell Sci. 1998 Aug; 111 ( Pt 15):2189-95.
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      138. Schneider H, Harbottle RP, Yokosaki Y, Kunde J, Sheppard D, Coutelle C. A novel peptide, PLAEIDGIELTY, for the targeting of alpha9beta1-integrins. FEBS Lett. 1998 Jun 16; 429(3):269-73.
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      139. Yokosaki Y, Matsuura N, Higashiyama S, Murakami I, Obara M, Yamakido M, Shigeto N, Chen J, Sheppard D. Identification of the ligand binding site for the integrin alpha9 beta1 in the third fibronectin type III repeat of tenascin-C. J Biol Chem. 1998 May 8; 273(19):11423-8.
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      140. Corry DB, Grünig G, Hadeiba H, Kurup VP, Warnock ML, Sheppard D, Rennick DM, Locksley RM. Requirements for allergen-induced airway hyperreactivity in T and B cell-deficient mice. Mol Med. 1998 May; 4(5):344-55.
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      141. Lansdell KA, Delaney SJ, Lunn DP, Thomson SA, Sheppard DN, Wainwright BJ. Comparison of the gating behaviour of human and murine cystic fibrosis transmembrane conductance regulator Cl- channels expressed in mammalian cells. J Physiol. 1998 Apr 15; 508 ( Pt 2):379-92.
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      142. Basora N, Desloges N, Chang Q, Bouatrouss Y, Gosselin J, Poisson J, Sheppard D, Beaulieu JF. Expression of the alpha9beta1 integrin in human colonic epithelial cells: resurgence of the fetal phenotype in a subset of colon cancers and adenocarcinoma cell lines. Int J Cancer. 1998 Mar 2; 75(5):738-43.
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      143. Cass DL, Bullard KM, Sylvester KG, Yang EY, Sheppard D, Herlyn M, Adzick NS. Epidermal integrin expression is upregulated rapidly in human fetal wound repair. J Pediatr Surg. 1998 Feb; 33(2):312-6.
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      144. Agrez MV, Shafren DR, Gu X, Cox K, Sheppard D, Barry RD. Integrin alpha v beta 6 enhances coxsackievirus B1 lytic infection of human colon cancer cells. Virology. 1997 Dec 8; 239(1):71-7.
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      145. Ramos DM, Chen BL, Boylen K, Stern M, Kramer RH, Sheppard D, Nishimura SL, Greenspan D, Zardi L, Pytela R. Stromal fibroblasts influence oral squamous-cell carcinoma cell interactions with tenascin-C. Int J Cancer. 1997 Jul 17; 72(2):369-76.
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      146. Smith LL, Cheung HK, Ling LE, Chen J, Sheppard D, Pytela R, Giachelli CM. Osteopontin N-terminal domain contains a cryptic adhesive sequence recognized by alpha9beta1 integrin. J Biol Chem. 1996 Nov 8; 271(45):28485-91.
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      147. Wang A, Yokosaki Y, Ferrando R, Balmes J, Sheppard D. Differential regulation of airway epithelial integrins by growth factors. Am J Respir Cell Mol Biol. 1996 Nov; 15(5):664-72.
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      148. Chen J, Maeda T, Sekiguchi K, Sheppard D. Distinct structural requirements for interaction of the integrins alpha 5 beta 1, alpha v beta 5, and alpha v beta 6 with the central cell binding domain in fibronectin. Cell Adhes Commun. 1996 Nov; 4(4-5):237-50.
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      149. Hérard AL, Pierrot D, Hinnrasky J, Kaplan H, Sheppard D, Puchelle E, Zahm JM. Fibronectin and its alpha 5 beta 1-integrin receptor are involved in the wound-repair process of airway epithelium. Am J Physiol. 1996 Nov; 271(5 Pt 1):L726-33.
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      150. Dixit RB, Chen A, Chen J, Sheppard D. Identification of a sequence within the integrin beta6 subunit cytoplasmic domain that is required to support the specific effect of alphavbeta6 on proliferation in three-dimensional culture. J Biol Chem. 1996 Oct 18; 271(42):25976-80.
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      151. Yokosaki Y, Monis H, Chen J, Sheppard D. Differential effects of the integrins alpha9beta1, alphavbeta3, and alphavbeta6 on cell proliferative responses to tenascin. Roles of the beta subunit extracellular and cytoplasmic domains. J Biol Chem. 1996 Sep 27; 271(39):24144-50.
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      152. Sheppard D. Epithelial integrins. Bioessays. 1996 Aug; 18(8):655-60.
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      153. Huang XZ, Wu JF, Cass D, Erle DJ, Corry D, Young SG, Farese RV, Sheppard D. Inactivation of the integrin beta 6 subunit gene reveals a role of epithelial integrins in regulating inflammation in the lung and skin. J Cell Biol. 1996 May; 133(4):921-8.
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      154. Agrez MV, Bates RC, Mitchell D, Wilson N, Ferguson N, Anseline P, Sheppard D. Multiplicity of fibronectin-binding alpha V integrin receptors in colorectal cancer. Br J Cancer. 1996 Apr; 73(7):887-92.
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      155. Wang A, Patrone L, McDonald JA, Sheppard D. Expression of the integrin subunit alpha 9 in the murine embryo. Dev Dyn. 1995 Dec; 204(4):421-31.
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      156. Kumar NM, Sigurdson SL, Sheppard D, Lwebuga-Mukasa JS. Differential modulation of integrin receptors and extracellular matrix laminin by transforming growth factor-beta 1 in rat alveolar epithelial cells. Exp Cell Res. 1995 Dec; 221(2):385-94.
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      157. Boylan AM, Sanan DA, Sheppard D, Broaddus VC. Vitronectin enhances internalization of crocidolite asbestos by rabbit pleural mesothelial cells via the integrin alpha v beta 5. J Clin Invest. 1995 Oct; 96(4):1987-2001.
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      158. Schnapp LM, Hatch N, Ramos DM, Klimanskaya IV, Sheppard D, Pytela R. The human integrin alpha 8 beta 1 functions as a receptor for tenascin, fibronectin, and vitronectin. J Biol Chem. 1995 Sep 29; 270(39):23196-202.
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      159. Huang XZ, Chen A, Agrez M, Sheppard D. A point mutation in the integrin beta 6 subunit abolishes both alpha v beta 6 binding to fibronectin and receptor localization to focal contacts. Am J Respir Cell Mol Biol. 1995 Aug; 13(2):245-51.
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      160. Weinacker A, Ferrando R, Elliott M, Hogg J, Balmes J, Sheppard D. Distribution of integrins alpha v beta 6 and alpha 9 beta 1 and their known ligands, fibronectin and tenascin, in human airways. Am J Respir Cell Mol Biol. 1995 May; 12(5):547-56.
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      161. Stepp MA, Zhu L, Sheppard D, Cranfill RL. Localized distribution of alpha 9 integrin in the cornea and changes in expression during corneal epithelial cell differentiation. J Histochem Cytochem. 1995 Apr; 43(4):353-62.
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      162. Schnapp LM, Breuss JM, Ramos DM, Sheppard D, Pytela R. Sequence and tissue distribution of the human integrin alpha 8 subunit: a beta 1-associated alpha subunit expressed in smooth muscle cells. J Cell Sci. 1995 Feb; 108 ( Pt 2):537-44.
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      163. Nikkari L, Haapasalmi K, Aho H, Torvinen A, Sheppard D, Larjava H, Heino J. Localization of the alpha v subfamily of integrins and their putative ligands in synovial lining cell layer. J Rheumatol. 1995 Jan; 22(1):16-23.
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      164. Massion PP, Hébert CA, Leong S, Chan B, Inoue H, Grattan K, Sheppard D, Nadel JA. Staphylococcus aureus stimulates neutrophil recruitment by stimulating interleukin-8 production in dog trachea. Am J Physiol. 1995 Jan; 268(1 Pt 1):L85-94.
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      165. Nishimura SL, Sheppard D, Pytela R. Integrin alpha v beta 8. Interaction with vitronectin and functional divergence of the beta 8 cytoplasmic domain. J Biol Chem. 1994 Nov 18; 269(46):28708-15.
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      166. Yokosaki Y, Palmer EL, Prieto AL, Crossin KL, Bourdon MA, Pytela R, Sheppard D. The integrin alpha 9 beta 1 mediates cell attachment to a non-RGD site in the third fibronectin type III repeat of tenascin. J Biol Chem. 1994 Oct 28; 269(43):26691-6.
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      167. Agrez M, Chen A, Cone RI, Pytela R, Sheppard D. The alpha v beta 6 integrin promotes proliferation of colon carcinoma cells through a unique region of the beta 6 cytoplasmic domain. J Cell Biol. 1994 Oct; 127(2):547-56.
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      168. Lukashev ME, Sheppard D, Pytela R. Disruption of integrin function and induction of tyrosine phosphorylation by the autonomously expressed beta 1 integrin cytoplasmic domain. J Biol Chem. 1994 Jul 15; 269(28):18311-4.
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      169. Sheppard D. Dominant negative mutants: tools for the study of protein function in vitro and in vivo. Am J Respir Cell Mol Biol. 1994 Jul; 11(1):1-6.
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      170. Cone RI, Weinacker A, Chen A, Sheppard D. Effects of beta subunit cytoplasmic domain deletions on the recruitment of the integrin alpha v beta 6 to focal contacts. Cell Adhes Commun. 1994 Jun; 2(2):101-13.
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      171. Weinacker A, Chen A, Agrez M, Cone RI, Nishimura S, Wayner E, Pytela R, Sheppard D. Role of the integrin alpha v beta 6 in cell attachment to fibronectin. Heterologous expression of intact and secreted forms of the receptor. J Biol Chem. 1994 Mar 4; 269(9):6940-8.
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      172. Pytela R, Suzuki S, Breuss J, Erle DJ, Sheppard D. Polymerase chain reaction cloning with degenerate primers: homology-based identification of adhesion molecules. Methods Enzymol. 1994; 245:420-51.
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      173. Palmer EL, Rüegg C, Ferrando R, Pytela R, Sheppard D. Sequence and tissue distribution of the integrin alpha 9 subunit, a novel partner of beta 1 that is widely distributed in epithelia and muscle. J Cell Biol. 1993 Dec; 123(5):1289-97.
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      174. Sheppard D. Identification and characterization of novel airway epithelial integrins. Am Rev Respir Dis. 1993 Dec; 148(6 Pt 2):S38-42.
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      175. Breuss JM, Gillett N, Lu L, Sheppard D, Pytela R. Restricted distribution of integrin beta 6 mRNA in primate epithelial tissues. J Histochem Cytochem. 1993 Oct; 41(10):1521-7.
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      176. Royce S, Wald P, Sheppard D, Balmes J. Occupational asthma in a pesticides manufacturing worker. Chest. 1993 Jan; 103(1):295-6.
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      177. Sheppard D, Cohen DS, Wang A, Busk M. Transforming growth factor beta differentially regulates expression of integrin subunits in guinea pig airway epithelial cells. J Biol Chem. 1992 Aug 25; 267(24):17409-14.
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      178. Busk M, Pytela R, Sheppard D. Characterization of the integrin alpha v beta 6 as a fibronectin-binding protein. J Biol Chem. 1992 Mar 25; 267(9):5790-6.
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      179. Sheppard D, Erle D, Busk M, Pytela R. Identification of novel airway epithelial integrins using the homology-based polymerase chain reaction. Chest. 1992 Mar; 101(3 Suppl):49S.
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      180. Gordon T, Balmes J, Fine J, Sheppard D. Airway oedema and obstruction in guinea pigs exposed to inhaled endotoxin. Br J Ind Med. 1991 Sep; 48(9):629-35.
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      181. Wang A, Cohen DS, Palmer E, Sheppard D. Polarized regulation of fibronectin secretion and alternative splicing by transforming growth factor. J Biol Chem. 1991 Aug 25; 266(24):15598-601.
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      182. Erle DJ, Sheppard D, Breuss J, Rüegg C, Pytela R. Novel integrin alpha and beta subunit cDNAs identified in airway epithelial cells and lung leukocytes using the polymerase chain reaction. Am J Respir Cell Mol Biol. 1991 Aug; 5(2):170-7.
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      183. Cohen DS, Palmer E, Welch WJ, Sheppard D. The response of guinea pig airway epithelial cells and alveolar macrophages to environmental stress. Am J Respir Cell Mol Biol. 1991 Aug; 5(2):133-43.
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      184. Erle DJ, Rüegg C, Sheppard D, Pytela R. Complete amino acid sequence of an integrin beta subunit (beta 7) identified in leukocytes. J Biol Chem. 1991 Jun 15; 266(17):11009-16.
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      185. Aris R, Christian D, Sheppard D, Balmes JR. Lack of bronchoconstrictor response to sulfuric acid aerosols and fogs. Am Rev Respir Dis. 1991 Apr; 143(4 Pt 1):744-50.
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      186. Aris R, Christian D, Sheppard D, Balmes JR. The effects of sequential exposure to acidic fog and ozone on pulmonary function in exercising subjects. Am Rev Respir Dis. 1991 Jan; 143(1):85-91.
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      187. Sheppard D, Rozzo C, Starr L, Quaranta V, Erle DJ, Pytela R. Complete amino acid sequence of a novel integrin beta subunit (beta 6) identified in epithelial cells using the polymerase chain reaction. J Biol Chem. 1990 Jul 15; 265(20):11502-7.
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      188. Aris R, Christian D, Sheppard D, Balmes JR. Acid fog-induced bronchoconstriction. The role of hydroxymethanesulfonic acid. Am Rev Respir Dis. 1990 Mar; 141(3):546-51.
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      189. Balmes JR, Fine JM, Gordon T, Sheppard D. Potential bronchoconstrictor stimuli in acid fog. Environ Health Perspect. 1989 Feb; 79:163-6.
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      190. Fine JM, Gordon T, Sheppard D. Epithelium removal alters responsiveness of guinea pig trachea to substance P. J Appl Physiol (1985). 1989 Jan; 66(1):232-7.
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      191. Sheppard D. Sulfur dioxide and asthma--a double-edged sword? J Allergy Clin Immunol. 1988 Dec; 82(6):961-4.
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      192. Sheppard D, Scypinski L. A tachykinin receptor antagonist inhibits and an inhibitor of tachykinin metabolism potentiates toluene diisocyanate-induced airway hyperresponsiveness in guinea pigs. Am Rev Respir Dis. 1988 Sep; 138(3):547-51.
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      193. Balmes JR, Fine JM, Christian D, Gordon T, Sheppard D. Acidity potentiates bronchoconstriction induced by hypoosmolar aerosols. Am Rev Respir Dis. 1988 Jul; 138(1):35-9.
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      194. Gordon T, Thompson JE, Sheppard D. Arachidonic acid metabolites do not mediate toluene diisocyanate-induced airway hyperresponsiveness in guinea pigs. Prostaglandins. 1988 May; 35(5):699-706.
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      195. Gordon T, Sheppard D. Tumor necrosis factor inhibits a polymorphonuclear leukocyte-dependent airway edema in guinea pigs. J Appl Physiol (1985). 1988 Apr; 64(4):1688-92.
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      196. Sheppard D, Thompson JE, Scypinski L, Dusser D, Nadel JA, Borson DB. Toluene diisocyanate increases airway responsiveness to substance P and decreases airway neutral endopeptidase. J Clin Invest. 1988 Apr; 81(4):1111-5.
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      197. Turner JR, Corkery KJ, Eckman D, Gelb AM, Lipavsky A, Sheppard D. Equivalence of continuous flow nebulizer and metered-dose inhaler with reservoir bag for treatment of acute airflow obstruction. Chest. 1988 Mar; 93(3):476-81.
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      198. Thompson JE, Sheppard D. Phosphoramidon potentiates the increase in lung resistance mediated by tachykinins in guinea pigs. Am Rev Respir Dis. 1988 Feb; 137(2):337-40.
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      199. Sheppard D. Mechanisms of acute increases in airway responsiveness caused by environmental chemicals. J Allergy Clin Immunol. 1988 Jan; 81(1):128-32.
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      200. Fine JM, Gordon T, Sheppard D. The roles of pH and ionic species in sulfur dioxide- and sulfite-induced bronchoconstriction. Am Rev Respir Dis. 1987 Nov; 136(5):1122-6.
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      201. Balmes JR, Fine JM, Sheppard D. Symptomatic bronchoconstriction after short-term inhalation of sulfur dioxide. Am Rev Respir Dis. 1987 Nov; 136(5):1117-21.
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      202. Sheppard D. What does exercise have to do with "exercise-induced" asthma? Am Rev Respir Dis. 1987 Sep; 136(3):547-9.
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      203. Thompson JE, Scypinski LA, Gordon T, Sheppard D. Tachykinins mediate the acute increase in airway responsiveness caused by toluene diisocyanate in guinea pigs. Am Rev Respir Dis. 1987 Jul; 136(1):43-9.
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      204. Gordon T, Milligan SA, Levin J, Thompson JE, Fine JM, Sheppard D. Apparent effect of catalase on airway edema in guinea pigs. Role of endotoxin contamination. Am Rev Respir Dis. 1987 Apr; 135(4):854-9.
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      205. Fine JM, Gordon T, Thompson JE, Sheppard D. The role of titratable acidity in acid aerosol-induced bronchoconstriction. Am Rev Respir Dis. 1987 Apr; 135(4):826-30.
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      206. Sheppard D. Physiology of the parasympathetic nervous system of the lung. Postgrad Med J. 1987; 63 Suppl 1:21-7.
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      207. Thompson JE, Scypinski LA, Gordon T, Sheppard D. Hydroxyurea inhibits airway hyperresponsiveness in guinea pigs by a granulocyte-independent mechanism. Am Rev Respir Dis. 1986 Dec; 134(6):1213-8.
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      208. Sheppard D. Mechanisms of bronchoconstriction from nonimmunologic environmental stimuli. Chest. 1986 Oct; 90(4):584-7.
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      209. Myers DJ, Bigby BG, Calvayrac P, Sheppard D, Boushey HA. Interaction of cromolyn and a muscarinic antagonist in inhibiting bronchial reactivity to sulfur dioxide and to eucapnic hyperpnea alone. Am Rev Respir Dis. 1986 Jun; 133(6):1154-8.
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      210. Sheppard D, Scypinski L, Horn J, Gordon T, Thompson JE. Granulocyte-mediated airway edema in guinea pigs. J Appl Physiol (1985). 1986 Apr; 60(4):1213-20.
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      211. Bigby TD, Margolskee D, Curtis JL, Michael PF, Sheppard D, Hadley WK, Hopewell PC. The usefulness of induced sputum in the diagnosis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. Am Rev Respir Dis. 1986 Apr; 133(4):515-8.
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      212. Sheppard D, DiStefano S, Byrd RC, Eschenbacher WL, Bell V, Steck J, Laddu A. Effects of esmolol on airway function in patients with asthma. J Clin Pharmacol. 1986 Mar; 26(3):169-74.
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      213. Sheppard D, Distefano S, Morse L, Becker C. Acute effects of routine firefighting on lung function. Am J Ind Med. 1986; 9(4):333-40.
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      214. Gordon T, Sheppard D, McDonald DM, Distefano S, Scypinski L. Airway hyperresponsiveness and inflammation induced by toluene diisocyanate in guinea pigs. Am Rev Respir Dis. 1985 Nov; 132(5):1106-12.
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      215. Tam EK, Geffroy BA, Myers DJ, Seltzer J, Sheppard D, Boushey HA. Effect of eucapnic hypoxia on bronchomotor tone and on the bronchomotor response to dry air in asthmatic subjects. Am Rev Respir Dis. 1985 Sep; 132(3):690-3.
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      216. Siegel D, Sheppard D, Gelb A, Weinberg PF. Aminophylline increases the toxicity but not the efficacy of an inhaled beta-adrenergic agonist in the treatment of acute exacerbations of asthma. Am Rev Respir Dis. 1985 Aug; 132(2):283-6.
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      217. Eschenbacher WL, Sheppard D. Respiratory heat loss is not the sole stimulus for bronchoconstriction induced by isocapnic hyperpnea with dry air. Am Rev Respir Dis. 1985 Jun; 131(6):894-901.
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      218. Sheppard D. Pharmacotherapy of asthma. West J Med. 1985 May; 142(5):700-2.
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      219. Bethel RA, Sheppard D, Geffroy B, Tam E, Nadel JA, Boushey HA. Effect of 0.25 ppm sulfur dioxide on airway resistance in freely breathing, heavily exercising, asthmatic subjects. Am Rev Respir Dis. 1985 Apr; 131(4):659-61.
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      220. Sheppard D, Eschenbacher WL, Epstein J. Lack of bronchomotor response to up to 3 ppm formaldehyde in subjects with asthma. Environ Res. 1984 Oct; 35(1):133-9.
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      221. Eschenbacher WL, Bethel RA, Boushey HA, Sheppard D. Morphine sulfate inhibits bronchoconstriction in subjects with mild asthma whose responses are inhibited by atropine. Am Rev Respir Dis. 1984 Sep; 130(3):363-7.
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      222. Bethel RA, Sheppard D, Epstein J, Tam E, Nadel JA, Boushey HA. Interaction of sulfur dioxide and dry cold air in causing bronchoconstriction in asthmatic subjects. J Appl Physiol Respir Environ Exerc Physiol. 1984 Aug; 57(2):419-23.
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      223. Sheppard D, Eschenbacher WL, Boushey HA, Bethel RA. Magnitude of the interaction between the bronchomotor effects of sulfur dioxide and those of dry (cold) air. Am Rev Respir Dis. 1984 Jul; 130(1):52-5.
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      224. Sheppard D, Eschenbacher WL. Respiratory water loss as a stimulus to exercise-induced bronchoconstriction. J Allergy Clin Immunol. 1984 May; 73(5 Pt 2):640-2.
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      225. Eschenbacher WL, Boushey HA, Sheppard D. Alteration in osmolarity of inhaled aerosols cause bronchoconstriction and cough, but absence of a permeant anion causes cough alone. Am Rev Respir Dis. 1984 Feb; 129(2):211-5.
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      226. Sheppard D, Epstein J, Skoogh BE, Bethel RA, Nadel JA, Boushey HA. Variable inhibition of histamine-induced bronchoconstriction by atropine in subjects with asthma. J Allergy Clin Immunol. 1984 Jan; 73(1 Pt 1):82-7.
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      227. Bethel RA, Epstein J, Sheppard D, Nadel JA, Boushey HA. Sulfur dioxide-induced bronchoconstriction in freely breathing, exercising, asthmatic subjects. Am Rev Respir Dis. 1983 Dec; 128(6):987-90.
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      228. Bethel RA, Erle DJ, Epstein J, Sheppard D, Nadel JA, Boushey HA. Effect of exercise rate and route of inhalation on sulfur-dioxide-induced bronchoconstriction in asthmatic subjects. Am Rev Respir Dis. 1983 Oct; 128(4):592-6.
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      229. Skoogh BE, Nadel JA, Fabbri LM, Sheppard D, Holtzman MJ. Antihistaminic versus anticholinergic effects of atropine on canine trachealis muscle. Am Rev Respir Dis. 1983 Oct; 128(4):603-6.
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      230. Sheppard D, Rizk NW, Boushey HA, Bethel RA. Mechanism of cough and bronchoconstriction induced by distilled water aerosol. Am Rev Respir Dis. 1983 Jun; 127(6):691-4.
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      231. Woo OF, Healey KM, Sheppard D, Tong TG. Chest pain and hypoxemia from inhalation of a trichloroethane aerosol product. J Toxicol Clin Toxicol. 1983 Jun; 20(4):333-41.
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      232. Sheppard D, Epstein J, Bethel RA, Nadel JA, Boushey HA. Tolerance to sulfur dioxide-induced bronchoconstriction in subjects with asthma. Environ Res. 1983 Apr; 30(2):412-9.
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      233. Sheppard D, Epstein J, Holtzman MJ, Nadel JA, Boushey HA. Effect of route of atropine delivery on bronchospasm from cold air and methacholine. J Appl Physiol Respir Environ Exerc Physiol. 1983 Jan; 54(1):130-3.
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      234. Holtzman MJ, McNamara MP, Sheppard D, Fabbri LM, Hahn HL, Graf PD, Nadel JA. Intravenous versus inhaled atropine for inhibiting bronchoconstrictor responses in dogs. J Appl Physiol Respir Environ Exerc Physiol. 1983 Jan; 54(1):134-9.
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      235. Sheppard D. Occupational asthma. West J Med. 1982 Dec; 137(6):480-5.
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      236. Kirkpatrick MB, Sheppard D, Nadel JA, Boushey HA. Effect of the oronasal breathing route on sulfur dioxide-induced bronchoconstriction in exercising asthmatic subjects. Am Rev Respir Dis. 1982 Jun; 125(6):627-31.
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      237. Sheppard D, Nadel JA, Boushey HA. Inhibition of sulfur dioxide-induced bronchoconstriction by disodium cromoglycate in asthmatic subjects. Am Rev Respir Dis. 1981 Sep; 124(3):257-9.
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      238. Sheppard D, Saisho A, Nadel JA, Boushey HA. Exercise increases sulfur dioxide-induced bronchoconstriction in asthmatic subjects. Am Rev Respir Dis. 1981 May; 123(5):486-91.
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      239. Sheppard D, Wong WS, Uehara CF, Nadel JA, Boushey HA. Lower threshold and greater bronchomotor responsiveness of asthmatic subjects to sulfur dioxide. Am Rev Respir Dis. 1980 Dec; 122(6):873-8.
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