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Stephen Nishimura, MD

Title(s)Professor, Pathology
SchoolSchool of Medicine
Phone415-206-5906
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    Collapse Biography 
    Collapse Education and Training
    University of California, San FranciscoResidency School of Medicine

    Collapse Research 
    Collapse Research Activities and Funding
    Structural mechanism of integrin-mediated TGF-b activation
    NIH/NHLBI R01HL134183Jul 4, 2016 - Apr 30, 2020
    Role: Principal Investigator
    Role of genetic variation in TGF-beta overactivation in COPD
    NIH/NHLBI R01HL113032Apr 1, 2012 - Mar 31, 2016
    Role: Principal Investigator
    Role of Squamous Metaplasia in Small Airways Disease in COPD
    NIH/NHLBI R01HL090662Sep 1, 2009 - Aug 31, 2011
    Role: Principal Investigator
    Integrin Regulation of Airway Epithelial Proliferation
    NIH/NHLBI K02HL070622Aug 1, 2002 - Jul 31, 2007
    Role: Principal Investigator
    Integrative Study of Brain Vascular Malformations
    NIH/NINDS P01NS044155Jul 1, 2002 - Mar 31, 2014
    Role: Co-Investigator
    Integrin alphavbeta8 Inhibits Airway Epithelial Cell Growth
    NIH/NHLBI R01HL063993Dec 1, 1999 - Mar 31, 2013
    Role: Principal Investigator
    DISTRIBUTION AND FUNCTION OF THE INTEGRIN ANDYB8
    NIH/NCI K08CA063148Jul 1, 1995 - Jun 30, 2001
    Role: Principal Investigator
    INTEGRINS AND BLASTOCYST-ENDOMETRIAL INTERACTION
    NIH/NCI F32CA009335Feb 10, 1993
    Role: Principal Investigator

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    Collapse Bibliographic 
    Collapse 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.
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    1. Takasaka N, Seed RI, Cormier A, Bondesson AJ, Lou J, Elattma A, Ito S, Yanagisawa H, Hashimoto M, Ma R, Levine MD, Publicover J, Potts R, Jespersen JM, Campbell MG, Conrad F, Marks JD, Cheng Y, Baron JL, Nishimura SL. Integrin avß8-expressing tumor cells evade host immunity by regulating TGF-ß activation in immune cells. JCI Insight. 2018 Oct 18; 3(20). PMID: 30333313.
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    2. Cormier A, Campbell MG, Ito S, Wu S, Lou J, Marks J, Baron JL, Nishimura SL, Cheng Y. Cryo-EM structure of the avß8 integrin reveals a mechanism for stabilizing integrin extension. Nat Struct Mol Biol. 2018 Aug; 25(8):698-704. PMID: 30061598.
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    3. Publicover J, Gaggar A, Jespersen JM, Halac U, Johnson AJ, Goodsell A, Avanesyan L, Nishimura SL, Holdorf M, Mansfield KG, Judge JB, Koshti A, Croft M, Wakil AE, Rosenthal P, Pai E, Cooper S, Baron JL. An OX40/OX40L interaction directs successful immunity to hepatitis B virus. Sci Transl Med. 2018 Mar 21; 10(433). PMID: 29563320.
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    4. Gotts JE, Chun L, Abbott J, Fang X, Takasaka N, Nishimura SL, Springer ML, Schick SF, Calfee CS, Matthay MA. Cigarette smoke exposure worsens acute lung injury in antibiotic-treated bacterial pneumonia in mice. Am J Physiol Lung Cell Mol Physiol. 2018 Jul 01; 315(1):L25-L40. PMID: 29543040.
      View in: PubMed
    5. Stockis J, Liénart S, Colau D, Collignon A, Nishimura SL, Sheppard D, Coulie PG, Lucas S. Blocking immunosuppression by human Tregs in vivo with antibodies targeting integrin aVß8. Proc Natl Acad Sci U S A. 2017 11 21; 114(47):E10161-E10168. PMID: 29109269.
      View in: PubMed
    6. Gotts JE, Abbott J, Fang X, Yanagisawa H, Takasaka N, Nishimura SL, Calfee CS, Matthay MA. Cigarette Smoke Exposure Worsens Endotoxin-Induced Lung Injury and Pulmonary Edema in Mice. Nicotine Tob Res. 2017 Sep 01; 19(9):1033-1039. PMID: 28340238.
      View in: PubMed
    7. Yanagisawa H, Hashimoto M, Minagawa S, Takasaka N, Ma R, Moermans C, Ito S, Araya J, Budelsky A, Goodsell A, Baron JL, Nishimura SL. Role of IL-17A in murine models of COPD airway disease. Am J Physiol Lung Cell Mol Physiol. 2017 01 01; 312(1):L122-L130. PMID: 27913421.
      View in: PubMed
    8. Ma L, Shen F, Jun K, Bao C, Kuo R, Young WL, Nishimura SL, Su H. Integrin ß8 Deletion Enhances Vascular Dysplasia and Hemorrhage in the Brain of Adult Alk1 Heterozygous Mice. Transl Stroke Res. 2016 12; 7(6):488-496. PMID: 27352867.
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    9. Publicover J, Jespersen JM, Johnson AJ, Nishimura SL, Goodsell A, Wakil AE, Rosenthal P, Pai E, Avanesyan L, Cooper S, Baron JL. Liver capsule: Age-influenced hepatic immune priming determines HBV infection fate: Implications from mouse to man. Hepatology. 2016 Jan; 63(1):260. PMID: 26457468.
      View in: PubMed
    10. Hashimoto M, Yanagisawa H, Minagawa S, Sen D, Ma R, Murray LA, Tsui P, Lou J, Marks JD, Baron JL, Krummel MF, Nishimura SL. TGF-ß-Dependent Dendritic Cell Chemokinesis in Murine Models of Airway Disease. J Immunol. 2015 Aug 01; 195(3):1182-90. PMID: 26109638; PMCID: PMC4506848.
      View in: PubMed, PubMed Central
    11. Brand OJ, Somanath S, Moermans C, Yanagisawa H, Hashimoto M, Cambier S, Markovics J, Bondesson AJ, Hill A, Jablons D, Wolters P, Lou J, Marks JD, Baron JL, Nishimura SL. Transforming Growth Factor-ß and Interleukin-1ß Signaling Pathways Converge on the Chemokine CCL20 Promoter. J Biol Chem. 2015 Jun 05; 290(23):14717-28. PMID: 25918170; PMCID: PMC4505537.
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    12. Hashimoto M, Yanagisawa H, Minagawa S, Sen D, Goodsell A, Ma R, Moermans C, McKnelly KJ, Baron JL, Krummel MF, Nishimura SL. A critical role for dendritic cells in the evolution of IL-1ß-mediated murine airway disease. J Immunol. 2015 Apr 15; 194(8):3962-9. PMID: 25786688.
      View in: PubMed
    13. Ito S, Araya J, Kurita Y, Kobayashi K, Takasaka N, Yoshida M, Hara H, Minagawa S, Wakui H, Fujii S, Kojima J, Shimizu K, Numata T, Kawaishi M, Odaka M, Morikawa T, Harada T, Nishimura SL, Kaneko Y, Nakayama K, Kuwano K. PARK2-mediated mitophagy is involved in regulation of HBEC senescence in COPD pathogenesis. Autophagy. 2015; 11(3):547-59. PMID: 25714760; PMCID: PMC4502689.
      View in: PubMed, PubMed Central
    14. Minagawa S, Lou J, Seed RI, Cormier A, Wu S, Cheng Y, Murray L, Tsui P, Connor J, Herbst R, Govaerts C, Barker T, Cambier S, Yanagisawa H, Goodsell A, Hashimoto M, Brand OJ, Cheng R, Ma R, McKnelly KJ, Wen W, Hill A, Jablons D, Wolters P, Kitamura H, Araya J, Barczak AJ, Erle DJ, Reichardt LF, Marks JD, Baron JL, Nishimura SL. Selective targeting of TGF-ß activation to treat fibroinflammatory airway disease. Sci Transl Med. 2014 Jun 18; 6(241):241ra79. PMID: 24944194; PMCID: PMC4341974.
      View in: PubMed, PubMed Central
    15. Wu TC, Xu K, Banchereau R, Marches F, Yu CI, Martinek J, Anguiano E, Pedroza-Gonzalez A, Snipes GJ, O'Shaughnessy J, Nishimura S, Liu YJ, Pascual V, Banchereau J, Oh S, Palucka K. Reprogramming tumor-infiltrating dendritic cells for CD103+ CD8+ mucosal T-cell differentiation and breast cancer rejection. Cancer Immunol Res. 2014 May; 2(5):487-500. PMID: 24795361; PMCID: PMC4014008.
      View in: PubMed, PubMed Central
    16. Lee TH, McKleroy W, Khalifeh-Soltani A, Sakuma S, Lazarev S, Riento K, Nishimura SL, Nichols BJ, Atabai K. Functional genomic screen identifies novel mediators of collagen uptake. Mol Biol Cell. 2014 Mar; 25(5):583-93. PMID: 24403604; PMCID: PMC3937085.
      View in: PubMed, PubMed Central
    17. Takasaka N, Araya J, Hara H, Ito S, Kobayashi K, Kurita Y, Wakui H, Yoshii Y, Yumino Y, Fujii S, Minagawa S, Tsurushige C, Kojima J, Numata T, Shimizu K, Kawaishi M, Kaneko Y, Kamiya N, Hirano J, Odaka M, Morikawa T, Nishimura SL, Nakayama K, Kuwano K. Autophagy induction by SIRT6 through attenuation of insulin-like growth factor signaling is involved in the regulation of human bronchial epithelial cell senescence. J Immunol. 2014 Feb 01; 192(3):958-68. PMID: 24367027.
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    18. Publicover J, Gaggar A, Nishimura S, Van Horn CM, Goodsell A, Muench MO, Reinhardt RL, van Rooijen N, Wakil AE, Peters M, Cyster JG, Erle DJ, Rosenthal P, Cooper S, Baron JL. Age-dependent hepatic lymphoid organization directs successful immunity to hepatitis B. J Clin Invest. 2013 Sep; 123(9):3728-39. PMID: 23925290; PMCID: PMC3754256.
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    19. Araya J, Kojima J, Takasaka N, Ito S, Fujii S, Hara H, Yanagisawa H, Kobayashi K, Tsurushige C, Kawaishi M, Kamiya N, Hirano J, Odaka M, Morikawa T, Nishimura SL, Kawabata Y, Hano H, Nakayama K, Kuwano K. Insufficient autophagy in idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 2013 Jan 01; 304(1):L56-69. PMID: 23087019.
      View in: PubMed
    20. Fujii S, Hara H, Araya J, Takasaka N, Kojima J, Ito S, Minagawa S, Yumino Y, Ishikawa T, Numata T, Kawaishi M, Hirano J, Odaka M, Morikawa T, Nishimura S, Nakayama K, Kuwano K. Insufficient autophagy promotes bronchial epithelial cell senescence in chronic obstructive pulmonary disease. Oncoimmunology. 2012 Aug 01; 1(5):630-641. PMID: 22934255.
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    21. Markovics JA, Araya J, Cambier S, Somanath S, Gline S, Jablons D, Hill A, Wolters PJ, Nishimura SL. Interleukin-1beta induces increased transcriptional activation of the transforming growth factor-beta-activating integrin subunit beta8 through altering chromatin architecture. J Biol Chem. 2011 Oct 21; 286(42):36864-74. PMID: 21878622; PMCID: PMC3196125.
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    22. Kitamura H, Cambier S, Somanath S, Barker T, Minagawa S, Markovics J, Goodsell A, Publicover J, Reichardt L, Jablons D, Wolters P, Hill A, Marks JD, Lou J, Pittet JF, Gauldie J, Baron JL, Nishimura SL. Mouse and human lung fibroblasts regulate dendritic cell trafficking, airway inflammation, and fibrosis through integrin avß8-mediated activation of TGF-ß. J Clin Invest. 2011 Jul; 121(7):2863-75. PMID: 21646718; PMCID: PMC3223836.
      View in: PubMed, PubMed Central
    23. Numata T, Araya J, Fujii S, Hara H, Takasaka N, Kojima J, Minagawa S, Yumino Y, Kawaishi M, Hirano J, Odaka M, Morikawa T, Nishimura SL, Nakayama K, Kuwano K. Insulin-dependent phosphatidylinositol 3-kinase/Akt and ERK signaling pathways inhibit TLR3-mediated human bronchial epithelial cell apoptosis. J Immunol. 2011 Jul 01; 187(1):510-9. PMID: 21646299.
      View in: PubMed
    24. Publicover J, Goodsell A, Nishimura S, Vilarinho S, Wang ZE, Avanesyan L, Spolski R, Leonard WJ, Cooper S, Baron JL. IL-21 is pivotal in determining age-dependent effectiveness of immune responses in a mouse model of human hepatitis B. J Clin Invest. 2011 Mar; 121(3):1154-62. PMID: 21393863; PMCID: PMC3049376.
      View in: PubMed, PubMed Central
    25. Minagawa S, Araya J, Numata T, Nojiri S, Hara H, Yumino Y, Kawaishi M, Odaka M, Morikawa T, Nishimura SL, Nakayama K, Kuwano K. Accelerated epithelial cell senescence in IPF and the inhibitory role of SIRT6 in TGF-ß-induced senescence of human bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2011 Mar; 300(3):L391-401. PMID: 21224216; PMCID: PMC3284316.
      View in: PubMed, PubMed Central
    26. Markovics JA, Araya J, Cambier S, Jablons D, Hill A, Wolters PJ, Nishimura SL. Transcription of the transforming growth factor beta activating integrin beta8 subunit is regulated by SP3, AP-1, and the p38 pathway. J Biol Chem. 2010 Aug 06; 285(32):24695-706. PMID: 20519498; PMCID: PMC2915706.
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    27. Arjomandi M, Seward J, Gotway MB, Nishimura S, Fulton GP, Thundiyil J, King TE, Harber P, Balmes JR. Low prevalence of chronic beryllium disease among workers at a nuclear weapons research and development facility. J Occup Environ Med. 2010 Jun; 52(6):647-52. PMID: 20523233; PMCID: PMC3313491.
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    28. Araya J, Nishimura SL. Fibrogenic reactions in lung disease. Annu Rev Pathol. 2010; 5:77-98. PMID: 20078216.
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    29. Su H, Kim H, Pawlikowska L, Kitamura H, Shen F, Cambier S, Markovics J, Lawton MT, Sidney S, Bollen AW, Kwok PY, Reichardt L, Young WL, Yang GY, Nishimura SL. Reduced expression of integrin alphavbeta8 is associated with brain arteriovenous malformation pathogenesis. Am J Pathol. 2010 Feb; 176(2):1018-27. PMID: 20019187; PMCID: PMC2808104.
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    30. Chesnokova LS, Nishimura SL, Hutt-Fletcher LM. Fusion of epithelial cells by Epstein-Barr virus proteins is triggered by binding of viral glycoproteins gHgL to integrins alphavbeta6 or alphavbeta8. Proc Natl Acad Sci U S A. 2009 Dec 01; 106(48):20464-9. PMID: 19920174; PMCID: PMC2787161.
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    31. Nishimura SL. Integrin-mediated transforming growth factor-beta activation, a potential therapeutic target in fibrogenic disorders. Am J Pathol. 2009 Oct; 175(4):1362-70. PMID: 19729474; PMCID: PMC2751532.
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    32. Zhu Y, Cuevas IC, Gabriel RA, Su H, Nishimura S, Gao P, Fields A, Hao Q, Young WL, Yang GY, Boudreau NJ. Restoring transcription factor HoxA5 expression inhibits the growth of experimental hemangiomas in the brain. J Neuropathol Exp Neurol. 2009 Jun; 68(6):626-32. PMID: 19458547; PMCID: PMC2728585.
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    33. Wilson SM, Barbone D, Yang TM, Jablons DM, Bueno R, Sugarbaker DJ, Nishimura SL, Gordon GJ, Broaddus VC. mTOR mediates survival signals in malignant mesothelioma grown as tumor fragment spheroids. Am J Respir Cell Mol Biol. 2008 Nov; 39(5):576-83. PMID: 18511708; PMCID: PMC2574528.
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    34. An F, Drummond DC, Wilson S, Kirpotin DB, Nishimura SL, Broaddus VC, Liu B. Targeted drug delivery to mesothelioma cells using functionally selected internalizing human single-chain antibodies. Mol Cancer Ther. 2008 Mar; 7(3):569-78. PMID: 18319332; PMCID: PMC2943512.
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    35. Vilarinho S, Ogasawara K, Nishimura S, Lanier LL, Baron JL. Blockade of NKG2D on NKT cells prevents hepatitis and the acute immune response to hepatitis B virus. Proc Natl Acad Sci U S A. 2007 Nov 13; 104(46):18187-92. PMID: 17991774; PMCID: PMC2084318.
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    36. 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. PMID: 17965775; PMCID: PMC2040320.
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    37. Araya J, Cambier S, Morris A, Finkbeiner W, Nishimura SL. Integrin-mediated transforming growth factor-beta activation regulates homeostasis of the pulmonary epithelial-mesenchymal trophic unit. Am J Pathol. 2006 Aug; 169(2):405-15. PMID: 16877343; PMCID: PMC1698780.
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    38. Diaz JV, Koff J, Gotway MB, Nishimura S, Balmes JR. Case report: a case of wood-smoke-related pulmonary disease. Environ Health Perspect. 2006 May; 114(5):759-62. PMID: 16675433.
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    39. 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. PMID: 16574941; PMCID: PMC2643260.
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    40. Kim KU, Wilson SM, Abayasiriwardana KS, Collins R, Fjellbirkeland L, Xu Z, Jablons DM, Nishimura SL, Broaddus VC. A novel in vitro model of human mesothelioma for studying tumor biology and apoptotic resistance. Am J Respir Cell Mol Biol. 2005 Dec; 33(6):541-8. PMID: 16123394; PMCID: PMC2715331.
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    41. Cambier S, Gline S, Mu D, Collins R, Araya J, Dolganov G, Einheber S, Boudreau N, Nishimura SL. Integrin alpha(v)beta8-mediated activation of transforming growth factor-beta by perivascular astrocytes: an angiogenic control switch. Am J Pathol. 2005 Jun; 166(6):1883-94. PMID: 15920172; PMCID: PMC1602409.
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    42. Gline SE, Cambier S, Govaerts C, Nishimura SL. A 50-A separation of the integrin alpha v beta 3 extracellular domain C termini reveals an intermediate activation state. J Biol Chem. 2004 Dec 24; 279(52):54567-72. PMID: 15475365.
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    43. Jackson T, Clark S, Berryman S, Burman A, Cambier S, Mu D, Nishimura S, King AM. Integrin alphavbeta8 functions as a receptor for foot-and-mouth disease virus: role of the beta-chain cytodomain in integrin-mediated infection. J Virol. 2004 May; 78(9):4533-40. PMID: 15078934; PMCID: PMC387692.
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    44. Morris DG, Jasmer RM, Huang L, Gotway MB, Nishimura S, King TE. Sarcoidosis following HIV infection: evidence for CD4+ lymphocyte dependence. Chest. 2003 Sep; 124(3):929-35. PMID: 12970019.
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    45. Fjellbirkeland L, Cambier S, Broaddus VC, Hill A, Brunetta P, Dolganov G, Jablons D, Nishimura SL. Integrin alphavbeta8-mediated activation of transforming growth factor-beta inhibits human airway epithelial proliferation in intact bronchial tissue. Am J Pathol. 2003 Aug; 163(2):533-42. PMID: 12875973; PMCID: PMC1868219.
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    46. Jarad G, Wang B, Khan S, DeVore J, Miao H, Wu K, Nishimura SL, Wible BA, Konieczkowski M, Sedor JR, Schelling JR. Fas activation induces renal tubular epithelial cell beta 8 integrin expression and function in the absence of apoptosis. J Biol Chem. 2002 Dec 06; 277(49):47826-33. PMID: 12324452.
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    47. 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. PMID: 11970960.
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    48. Baron JL, Gardiner L, Nishimura S, Shinkai K, Locksley R, Ganem D. Activation of a nonclassical NKT cell subset in a transgenic mouse model of hepatitis B virus infection. Immunity. 2002 Apr; 16(4):583-94. PMID: 11970881.
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    49. Cambier S, Mu DZ, O'Connell D, Boylen K, Travis W, Liu WH, Broaddus VC, Nishimura SL. A role for the integrin alphavbeta8 in the negative regulation of epithelial cell growth. Cancer Res. 2000 Dec 15; 60(24):7084-93. PMID: 11156415.
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    50. Morris AM, Nishimura S, Huang L. Subacute hypersensitivity pneumonitis in an HIV infected patient receiving antiretroviral therapy. Thorax. 2000 Jul; 55(7):625-7. PMID: 10856327; PMCID: PMC1745796.
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    51. Nishimura SL, Broaddus VC. Asbestos-induced pleural disease. Clin Chest Med. 1998 Jun; 19(2):311-29. PMID: 9646983.
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    52. Nishimura SL, Boylen KP, Einheber S, Milner TA, Ramos DM, Pytela R. Synaptic and glial localization of the integrin alphavbeta8 in mouse and rat brain. Brain Res. 1998 Apr 27; 791(1-2):271-82. PMID: 9593935.
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    53. 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. PMID: 9219848.
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    54. Breuss JM, Gallo J, DeLisser HM, Klimanskaya IV, Folkesson HG, Pittet JF, Nishimura SL, Aldape K, Landers DV, Carpenter W. Expression of the beta 6 integrin subunit in development, neoplasia and tissue repair suggests a role in epithelial remodeling. J Cell Sci. 1995 Jun; 108 ( Pt 6):2241-51. PMID: 7673344.
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    55. 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. PMID: 7525578.
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    56. 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 04; 269(9):6940-8. PMID: 8120056.
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    57. Frank UK, Nishimura SL, Li NC, Sugai K, Yajko DM, Hadley WK, Ng VL. Evaluation of an enzyme immunoassay for detection of cryptococcal capsular polysaccharide antigen in serum and cerebrospinal fluid. J Clin Microbiol. 1993 Jan; 31(1):97-101. PMID: 8417038; PMCID: PMC262628.
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    58. Perkocha LA, Geaghan SM, Yen TS, Nishimura SL, Chan SP, Garcia-Kennedy R, Honda G, Stoloff AC, Klein HZ, Goldman RL. Clinical and pathological features of bacillary peliosis hepatis in association with human immunodeficiency virus infection. N Engl J Med. 1990 Dec 06; 323(23):1581-6. PMID: 2233946.
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