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Laboratory Profile
  1. Development of a novel vaccine adjuvant using laser light
  2. Development of a novel immunotherapy for allergy using laser light
  • Principal investigator: Satoshi Kashiwagi, MD, PhD
  • Postdoctoral Research Fellows: Yoshifumi Kimizuka, MD, PhD
  • Hiroaki Shiratori, BA candidate
  • Shu Takeuchi, MD candidate
  • Conor Dwyer, BA candidate
  • Megan Chan, BA candidate
  • Rhea Tan, MD candidate
  • Benjamin Forbes, BA and MD candidate
  • Laura Whicher, BA
  • Beth Edelblute, BA and MD candidate
  • Brian Collette, BA
  • Laurel Edington, BA and MD candidate
  • Calum Goudie, MD candidate
  • Haaris Beg, BA candidate
  • Elia LebLanc, BA candidate
  • Yusuke Shomaoka, MD candidate
  • Kaitlyn Morse, PhD
  • Graduate Research Assistant: Ayako Shigeta, MD
  • Research Assistants: Mai Shibata, MD candidate
  1. Suematsu M, Kashiwagi S, Sano T, Goda N, Shinoda Y, Ishimura Y.

    Carbon monoxide as an endogenous modulator of hepatic vascular perfusion. Biochem Biophys Res Commun 1994; 205(2): 1333-1337.

    http://www.ncbi.nlm.nih.gov/pubmed/7802666
  2. Suematsu M, Goda N, Sano T, Kashiwagi S, Egawa T, Yuichi S, Ishimura Y.

    Carbon monoxide: An endogenous modulator of sinusoidal tone in the perfused rat liver. J Clin Invest 1995; 96: 2431-2437.

    http://www.ncbi.nlm.nih.gov/pubmed/7593631
  3. Kashiwagi S, Suematsu M, Wakabayashi Y, Koizumi A, Tachibana M, Kawada N, Inoue M, Ishimura Y, Kaneko A.

    Electrophysiological characterization of cultured hepatic stellate cells in rats. Am J Physiol (Gastrointest and Liver Physiol) 1997; 272: G742-G750.

    http://www.ncbi.nlm.nih.gov/pubmed/9142904
  4. Kashiwagi S, Kajimura M, Yoshimura Y, Suematsu M.

    Nonendothelial source of nitric oxide in arterioles but not in venules: Alternative source revealed in vivo by diaminofluorescein microfluorography. Circ Res 2002; 91: e55-e64.

    http://www.ncbi.nlm.nih.gov/pubmed/12480826
  5. Suematsu M, Suganuma K, Kashiwagi S

    Mechanistic probing of gaseous signal transduction in microcirculation. Antioxid Redox Signal 2003; 5(4): 485-492.

    http://www.ncbi.nlm.nih.gov/pubmed/13678537
  6. Kashiwagi S, Miyakoshi K, Ishimoto H, Tanaka M, Yoshimura Y.

    Checkmark fetal heart rate pattern associated with severe fetal hypoxia: A case report. Fetal Diagn Ther 2003; 18(4): 237-239.

    http://www.ncbi.nlm.nih.gov/pubmed/12835582
  7. Kudo A, Kashiwagi S, Kajimura M, Yoshimura Y, Uchida K, Arii S, Suematsu M.

    Kupffer cells alter organic anion transport through multidrug resistance protein 2 in the post-cold ischemic rat liver. Hepatology 2004; 34(4): 1099-1109.

    http://www.ncbi.nlm.nih.gov/pubmed/15057914
  8. Hagendoorn J, Padera TP, Kashiwagi S, Isaka N, Noda F, Lin MI, Huang PL, Sessa WC, Fukumura D, Jain RK.

    Endothelial nitric oxide synthase regulates microlymphatic flow via collecting lymphatics. Circ Res 2004; 95(2): 204-209.

    http://www.ncbi.nlm.nih.gov/pubmed/15192027
  9. Kashiwagi S, Izumi Y, Gohongi T, Demou ZN, Xu L, Huang PL, Buerk DG, Munn LL, Jain RK, Fukumura D.

    NO mediates mural cell recruitment and vessel morphogenesis in murine melanomas and tissue-engineered blood vessels. J Clin Invest 2005; 115(7): 1816–1827.

    http://www.ncbi.nlm.nih.gov/pubmed/15951843
  10. Xu L, Cochran DM, Tong RT, Winkler F, Kashiwagi S, Jain RK, Fukumura D.

    Placenta growth factor overexpression inhibits tumor growth, angiogenesis, and metastasis by depleting vascular endothelial growth factor homodimers in orthotopic mouse models. Cancer Res 2006; 66(8): 3971-3977.

    http://www.ncbi.nlm.nih.gov/pubmed/16618713
  11. Fukumura D, Kashiwagi S, Jain RK.

    Role of nitric oxide in tumour progression. Nat Rev Cancer 2006; 6(7): 521-534.

    http://www.ncbi.nlm.nih.gov/pubmed/16794635
  12. Yamashita T, Shoge M, Oda E, Yamamoto Y, Giddings JC, Kashiwagi S, Suematsu M, Yamamoto J.

    The free-radical scavenger, edaravone, auguments NO release from vascular cells and platelets after laser-induced, acute endothelial injury in vivo. Platelets 2006; 17(3): 201-206.

    http://www.ncbi.nlm.nih.gov/pubmed/16702048
  13. Lawenda BD, Smith D, Xu L, Niemierko A, Silverstein J, Boucher Y, Kashiwagi S, Held KD, Jain RK, Loeffler J, Blumberg JB.

    Do the dietary supplements EGCG or Vitamin E cause a radiomodifying response on tumors? A pilot study with murine breast carcinoma. J Soc Integr Oncol 2007; 5(1): 11-17.

    http://www.ncbi.nlm.nih.gov/pubmed/17309809
  14. Ogawa K, Boucher Y, Kashiwagi S, Fukumura D, Chen D, Gerweck LE.

    Influence of tumor cell and stroma sensitivity on tumor response to radiation. Cancer Res 2007; 67(9):4016-4021.

    http://www.ncbi.nlm.nih.gov/pubmed/17483312
  15. Kashiwagi S, Tsukada K, Xu L, Miyazaki J, Kozin SV, Tyrrell JA, Sessa WC, Gerweck LE, Jain RK, Fukumura D.

    Perivascular nitric oxide gradients normalize tumor vasculature. Nat Med 2008; 14(3): 255-257.

    http://www.ncbi.nlm.nih.gov/pubmed/18278052
  16. Lahdenranta J, Hagendoorn J, Padera TP, Hoshida T, Nelson G, Kashiwagi S, Jain RK, Fukumura D.

    Endothelial nitric oxide synthase mediates lymphangiogenesis and lymphatic metastasis. Cancer Res 2009; 69(7): 2801-2808.

    http://www.ncbi.nlm.nih.gov/pubmed/19318557
  17. Schleicher M, Yu J, Murata T, Derakhshan B, Atochin D, Qian L, Kashiwagi S, Di Lorenzo A, Harrison KD, Huang PL, Sessa WC.

    The Akt1-eNOS axis illustrates the specificity of kinase-substrate relationships in vivo. Sci Signal 2009; 2(82): ra41.

    http://www.ncbi.nlm.nih.gov/pubmed/19654415
  18. Hovav AH, Santosuosso M, Bivas-Benita M, Plair A, Cheng A, Elnekave M, Righi E, Chen T, Kashiwagi S, Panas MW, Shi-Hua X, Furmanov K, Letvin NL, Poznansky MC.

    X4 HIV-1 gp120 Down-Modulates Expression and Immunogenicity of Co-delivered Antigens. J Virol 2009; 83(21): 10941-10950.

    http://www.ncbi.nlm.nih.gov/pubmed/19692474
  19. Righi E*, Kashiwagi S*, Yuan J, Santosuosso M, Leblanc P, Ingraham R, Forbes B, Edelblute B, Collette B, Xing D, Kowalski M, Mingari MC, Vianello F, Birrer M, Orsulic S, Dranoff G, and Poznansky MC.

    CXCL12/CXCR4 blockade induces multimodal anti-tumor effects that prolong survival in an immunocompetent mouse model of ovarian cancer. Cancer Res, 2011; 71(16):5522-5534. *equally contributed.

    http://www.ncbi.nlm.nih.gov/pubmed/21742774
  20. Kashiwagi S, Atochin DN, Li Q, Schleicher M, Pong T, Sessa WC, Huang PL.

    eNOS phosphorylation on serine 1176 affects insulin sensitivity and adiposity. Biochem Biophys Res Commun, 2013; 431(2):284-290.

    http://www.ncbi.nlm.nih.gov/pubmed/23291238
  21. Ayata C, Shin HK, Dilekoez E, Atochin DN, Kashiwagi S, Eikermann-Haerter K, Huang PL.

    Hyperlipidemia disrupts cerebrovascular reflexes and worsens ischemic perfusion defect. J Cereb Blood Flow Metab, 2013; 33(6):954-62.

    http://www.ncbi.nlm.nih.gov/pubmed/23486293
  22. Li Q, Atochin D, Kashiwagi S, Earle J, Wang A, Mandeville E, Hayakawa K, d'Uscio L, Lo E, Katusic Z, Sessa W, Huang P.

    Deficient eNOS phosphorylation is a mechanism for diabetic vascular dysfunction contributing to increased stroke size. Stroke, 2013; 44(11):3183-8.

    http://www.ncbi.nlm.nih.gov/pubmed/23988642
  23. Kashiwagi S, Yuan J, Forbes B, Hibert ML, Lee ELQ, Whicher L, Goudie C, Yang Y, Chen T, Edelblute B, Collette B, Edington L, Trussler J, Nezivar J, Leblanc P, Bronson R, Tsukada K, Suematsu M, Dover J, Brauns T, Gelfand J, Poznansky MC.

    Near-infrared laser adjuvant for influenza vaccine. PLoS One, 2013; 8(12): e82899.

    http://www.ncbi.nlm.nih.gov/pubmed/24349390
  24. Yuan J, Kashiwagi S, Reeves P, Nezivar J, Yang Y, Arrifin NH, Nguyen M, Jean-Mary G, Tong X, Uppal P, Korochkina S, Forbes B, Chen T, Righi E, Bronson R, Chen H, Orsulic S, Brauns T, Leblanc P, Scholler N, Dranoff G, Gelfand J, Poznansky MC.

    A novel mycobacterial Hsp70-containing fusion protein targeting mesothelin augments antitumor immunity and prolongs survival in murine models of ovarian cancer and mesothelioma. J Hematol Oncol, 2014; 7(1):15.

    http://www.ncbi.nlm.nih.gov/pubmed/24565018
  25. Kashiwagi S, Brauns T, Gelfand J, Poznansky MC.

    Laser vaccine adjuvants: History, progress, and potential. Hum Vaccin Immunother 2014;10(7):1892-1907.

    http://www.ncbi.nlm.nih.gov/pubmed/24782161
  26. Chen T, Yuan J, Duncanson S, Hibert ML, Kodish BC, Mylavaganam G, Maker M, Li H, Sremac M, Santosuosso M, Forbes B, Kashiwagi S, Cao J, Lei J, Thomas M, Hartono C, Sachs D, Markmann J, Sambanis A, Poznansky MC.

    Alginate encapsulant incorporating CXCL12 supports long term allo and xenoislet transplantation without systemic immune suppression. Am J Transplant 2015;15(3):618-27.

    http://www.ncbi.nlm.nih.gov/pubmed/25693473
  27. Kimizuka Y, Callahan JJ, Huang Z, Morse K, Katagiri W, Shigeta A, Bronson R, Takeuchi S, Shimaoka Y, Chan MP, Zeng Y, Li B, Chen H, Tan RY, Dwyer C, Mulley T, Leblanc P, Goudie C, Gelfand J, Tsukada K, Brauns T, Poznansky MC, Bean D, Kashiwagi S

    Semiconductor diode laser device adjuvanting intradermal vaccine. Vaccine. 2017 Apr 25;35(18):2404-2412. doi: 10.1016/j.vaccine.2017.03.036. Epub 2017 Mar 30.

    https://www.ncbi.nlm.nih.gov/pubmed/28365253
  28. Morse K, Kimizuka Y, Chan MPK, Shibata M, Shimaoka Y, Takeuchi S, Forbes B, Nirschl C, Li B, Zeng Y, Bronson RT, Katagiri W, Shigeta A, Sîrbulescu RF, Chen H, Tan RYY, Tsukada K, Brauns T, Gelfand J, Sluder A, Locascio JJ, Poznansky MC, Anandasabapathy N, Kashiwagi S

    Near-infrared 1064 nm lase modulates migratory dendritic cells to augment the immune response to intradermal influenza vaccine. J Immunol. 2017 Aug 15;199(4):1319-1332. doi: 10.4049/jimmunol.1601873. Epub 2017 Jul 14.

    https://www.ncbi.nlm.nih.gov/pubmed/28710250