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Our Science – Klinman Website

Dennis M. Klinman, M.D., Ph.D.

Selected Publications

1)  Gursel M, Klinman D.
Use of CpG Oligonucleotides as Mucosal Adjuvants. In: Mucosal Immunology. Volume Chapter 62.
Elsevier Inc.; 2014. In Press. [Book Chapter]
2)  Shimada M, Yoshizaki S, Ichino M, Klinman DM, Okuda K.
Apoptosis of antigen-specific CTLs contributes to low immune response in gut-associated lymphoid tissue post vaccination.
Vaccine. [Epub ahead of print], 2014.
3)  Scheiermann J, Klinman DM.
Clinical evaluation of CpG oligonucleotides as adjuvants for vaccines targeting infectious diseases and cancer.
Vaccine. [Epub ahead of print], 2014.
4)  Zhao BG, Vasilakos JP, Tross D, Smirnov D, Klinman DM.
Combination therapy targeting toll like receptors 7, 8 and 9 eliminates large established tumors.
J Immunother Cancer. 2: 12, 2014.
5)  Hodge DL, Berthet C, Coppola V, Kastenmüller W, Buschman MD, Schaughency PM, Shirota H, Scarzello AJ, Subleski JJ, Anver MR, Ortaldo JR, Lin F, Reynolds DA, Sanford ME, Kaldis P, Tessarollo L, Klinman DM, Young HA.
IFN-gamma AU-rich element removal promotes chronic IFN-gamma expression and autoimmunity in mice.
J. Autoimmun. [Epub ahead of print], 2014.
6)  Shirota H, Klinman DM.
Recent progress concerning CpG DNA and its use as a vaccine adjuvant.
Expert Rev Vaccines. 13: 299-312, 2014.
7)  Bode C, Kinjo T, Alvord WG, Klinman DM.
Suppressive oligodeoxynucleotides reduce lung cancer susceptibility in mice with silicosis.
Carcinogenesis. 35: 1078-83, 2014.
8)  Shirota H, Klinman DM.
TLR-9 agonist immunostimulatory sequence adjuvants linked to cancer antigens.
Methods Mol. Biol. 1139: 337-44, 2014.
9)  Sui Y, Hogg A, Wang Y, Frey B, Yu H, Xia Z, Venzon D, McKinnon K, Smedley J, Gathuka M, Klinman D, Keele BF, Langermann S, Liu L, Franchini G, Berzofsky JA.
Vaccine-induced myeloid cell population dampens protective immunity to SIV.
J. Clin. Invest. 124: 2538-49, 2014.
10)  Shi G, Vistica BP, Nugent LF, Tan C, Wawrousek EF, Klinman DM, Gery I.
Differential Involvement of Th1 and Th17 in Pathogenic Autoimmune Processes Triggered by Different TLR Ligands.
J. Immunol. 191: 415-23, 2013.
11)  Steinhagen F, McFarland AP, Rodriguez LG, Tewary P, Jarret A, Savan R, Klinman DM.
IRF-5 and NF-?B p50 co-regulate IFN-ß and IL-6 expression in TLR9-stimulated human plasmacytoid dendritic cells.
Eur. J. Immunol. 43: 1896-906, 2013.
12)  Kobayashi N, Hong C, Klinman DM, Shirota H.
Oligodeoxynucleotides Expressing Polyguanosine Motifs Promote Antitumor Activity through the Upregulation of IL-2.
J. Immunol. 190: 1882-9, 2013.
13)  Gursel M, Klinman DM, Gursel I.
Plasmacytoid dendritic cell response to CpG ODN correlates with CXCL16 expression and is inhibited by ox-LDL.
Mediators Inflamm. 2013: 312590, 2013.
14)  Shimada M, Abe S, Takahashi T, Shiozaki K, Okuda M, Mizukami H, Klinman DM, Ozawa K, Okuda K.
Prophylaxis and treatment of Alzheimer"s disease by delivery of an adeno-associated virus encoding a monoclonal antibody targeting the amyloid Beta protein.
PLoS ONE. 8: e57606, 2013.
15)  Tewary P, de la Rosa G, Sharma N, Rodriguez LG, Tarasov SG, Howard OM, Shirota H, Steinhagen F, Klinman DM, Yang D, Oppenheim JJ.
ß-Defensin 2 and 3 Promote the Uptake of Self or CpG DNA, Enhance IFN-a Production by Human Plasmacytoid Dendritic Cells, and Promote Inflammation.
J. Immunol. 191: 865-74, 2013.
16)  Bode C, Yang XP, Kiu H, Klinman DM.
Suppressive oligodeoxynucleotides promote the development of th17 cells.
PLoS ONE. 8: e67991, 2013.
17)  Takahashi R, Sato T, Klinman DM, Shimosato T, Kaneko T, Ishigatsubo Y.
Suppressive oligodeoxynucleotides synergistically enhance antiproliferative effects of anticancer drugs in A549 human lung cancer cells.
Int. J. Oncol. 42: 429-36, 2013.
18)  Kaminski JJ, Schattgen SA, Tzeng TC, Bode C, Klinman DM, Fitzgerald KA.
Synthetic oligodeoxynucleotides containing suppressive TTAGGG motifs inhibit AIM2 inflammasome activation.
J. Immunol. 191: 3876-83, 2013.
19)  Shirota H, Klinman DM.
Use of CpG oligonucleotides for cancer immunotherapy and their effect on immunity in the tumor microenvironment.
Immunotherapy. 5: 787-9, 2013.
20)  Steinhagen F, Meyer C, Tross D, Gursel M, Maeda T, Klaschik S, Klinman DM.
Activation of type I interferon-dependent genes characterizes the.
J Leukoc Biol. 92: 775-85, 2012.
21)  Shirota H, Klinman DM.
Effect of CpG ODN on monocytic myeloid derived suppressor cells.
Oncoimmunology. 1: 780-782, 2012.
22)  Yang D, Postnikov YV, Li Y, Tewary P, de la Rosa G, Wei F, Klinman D, Gioannini T, Weiss JP, Furusawa T, Bustin M, Oppenheim JJ.
High-mobility group nucleosome-binding protein 1 acts as an alarmin and is critical for lipopolysaccharide-induced immune responses.
J. Exp. Med. 209: 157-71, 2012.
23)  Shirota Y, Shirota H, Klinman DM.
Intratumoral injection of CpG oligonucleotides induces the differentiation and reduces the immunosuppressive activity of myeloid-derived suppressor cells.
J. Immunol. 188: 1592-9, 2012.
24)  Zhu Q, Talton J, Zhang G, Cunningham T, Wang Z, Waters RC, Kirk J, Eppler B, Klinman DM, Sui Y, Gagnon S, Belyakov IM, Mumper RJ, Berzofsky JA.
Large intestine-targeted, nanoparticle-releasing oral vaccine to control genitorectal viral infection.
Nat Med. 18: 1291-6, 2012.
25)  Kinjo T, Tomaru K, Haines DC, Klinman DM.
The counter regulatory response induced by CpG oligonucleotides prevents bleomycin induced pneumopathy.
Respir Res. 13: 47, 2012.
26)  Savan R, McFarland AP, Reynolds DA, Feigenbaum L, Ramakrishnan K, Karwan M, Shirota H, Klinman DM, Dunleavy K, Pittaluga S, Anderson SK, Donnelly RP, Wilson WH, Young HA.
A novel role for IL-22R1 as a driver of inflammation.
Blood. 117: 575-84, 2011.
27)  Bode C, Zhao G, Steinhagen F, Kinjo T, Klinman DM.
CpG DNA as a vaccine adjuvant.
Expert Rev Vaccines. 10: 499-511, 2011.
28)  Shirota H, Klinman DM.
CpG-conjugated apoptotic tumor cells elicit potent tumor-specific immunity.
Cancer Immunol. Immunother. 60: 659-69, 2011.
29)  Ikeuchi H, Kinjo T, Klinman DM.
Effect of suppressive oligodeoxynucleotides on the development of inflammation-induced papillomas.
Cancer Prev Res (Phila). 4: 752-7, 2011.
30)  Qi J, Buzas K, Fan H, Cohen JI, Wang K, Mont E, Klinman D, Oppenheim JJ, Howard OM.
Painful pathways induced by TLR stimulation of dorsal root ganglion neurons.
J. Immunol. 186: 6417-26, 2011.
31)  Yamamoto M, Sato T, Beren J, Verthelyi D, Klinman DM.
The acceleration of wound healing in primates by the local administration of immunostimulatory CpG oligonucleotides.
Biomaterials. 32: 4238-42, 2011.
32)  Sui Y, Gagnon S, Dzutsev A, Zhu Q, Yu H, Hogg A, Wang Y, Xia Z, Belyakov IM, Venzon D, Klinman D, Strober W, Kelsall B, Franchini G, Berzofsky JA.
TLR agonists and/or IL-15 adjuvanted mucosal SIV vaccine reduced gut CD4⁺ memory T cell loss in SIVmac251-challenged rhesus macaques.
Vaccine. 30: 59-68, 2011.
33)  Steinhagen F, Kinjo T, Bode C, Klinman DM.
TLR-based immune adjuvants.
Vaccine. 29: 3341-55, 2011.
34)  Sato T, Yamamoto M, Shimosato T, Klinman DM.
Accelerated wound healing mediated by activation of Toll-like receptor 9.
Wound Repair Regen. 18: 586-93, 2010.
35)  Klinman DM, Klaschik S, Tross D, Shirota H, Steinhagen F.
FDA guidance on prophylactic DNA vaccines: analysis and recommendations.
Vaccine. 28: 2801-5, 2010.
36)  Klinman DM, Klaschik S, Tomaru K, Shirota H, Tross D, Ikeuchi H.
Immunostimulatory CpG oligonucleotides: Effect on gene expression and utility as vaccine adjuvants.
Vaccine. 28: 1919-23, 2010.
37)  Sui Y, Zhu Q, Gagnon S, Dzutsev A, Terabe M, Vaccari M, Venzon D, Klinman D, Strober W, Kelsall B, Franchini G, Belyakov IM, Berzofsky JA.
Innate and adaptive immune correlates of vaccine and adjuvant-induced control of mucosal transmission of SIV in macaques.
Proc. Natl. Acad. Sci. U.S.A. 107: 9843-8, 2010.
38)  Wang HB, Kondo A, Yoshida A, Yoshizaki S, Abe S, Bao LL, Mizuki N, Ichino M, Klinman D, Okuda K, Shimada M.
Partial protection against SIV challenge by vaccination of adenovirus and MVA vectors in rhesus monkeys.
Gene Ther. 17: 4-13, 2010.
39)  Klaschik S, Tross D, Shirota H, Klinman DM.
Short- and long-term changes in gene expression mediated by the activation of TLR9.
Mol. Immunol. 47: 1317-24, 2010.
40)  Zhu Q, Egelston C, Gagnon S, Sui Y, Belyakov IM, Klinman DM, Berzofsky JA.
Using 3 TLR ligands as a combination adjuvant induces qualitative changes in T cell responses needed for antiviral protection in mice.
J. Clin. Invest. 120: 607-16, 2010.
41)  Klinman DM, Tross D.
A single-dose combination therapy that both prevents and treats anthrax infection.
Vaccine. 27: 1811-5, 2009.
42)  Fujimoto C, Klinman DM, Shi G, Yin H, Vistica BP, Lovaas JD, Wawrousek EF, Igarashi T, Chan CC, Gery I.
A suppressive oligodeoxynucleotide inhibits ocular inflammation.
Clin. Exp. Immunol. 156: 528-34, 2009.
43)  Abe S, Okuda K, Ura T, Kondo A, Yoshida A, Yoshizaki S, Mizuguchi H, Klinman D, Shimada M.
Adenovirus type 5 with modified hexons induces robust transgene-specific immune responses in mice with pre-existing immunity against adenovirus type 5.
The journal of gene medicine. 11: 570-9, 2009.
44)  Klinman DM, Yamamoto M, Tross D, Tomaru K.
Anthrax prevention and treatment: utility of therapy combining antibiotic plus vaccine.
Expert Opin Biol Ther. 9: 1477-86, 2009.
45)  Shirota H, Petrenko L, Hattori T, Klinman DM.
Contribution of IRF-3 mediated IFNbeta production to DNA vaccine dependent cellular immune responses.
Vaccine. 27: 2144-9, 2009.
46)  Klinman DM, Klaschik S, Sato T, Tross D.
CpG oligonucleotides as adjuvants for vaccines targeting infectious diseases.
Adv. Drug Deliv. Rev. 61: 248-55, 2009.
47)  Shimada M, Wang HB, Kondo A, Xu XP, Yoshida A, Shinoda K, Ura T, Mizuguchi H, Klinman D, Luo JL, Bai H, Okuda K.
Effect of therapeutic immunization using Ad5/35 and MVA vectors on SIV infection of rhesus monkeys undergoing antiretroviral therapy.
Gene Ther. 16: 218-28, 2009.
48)  Tross D, Petrenko L, Klaschik S, Zhu Q, Klinman DM.
Global changes in gene expression and synergistic interactions induced by TLR9 and TLR3.
Mol. Immunol. 46: 2557-64, 2009.
49)  Sloane E, Langer S, Jekich B, Mahoney J, Hughes T, Frank M, Seibert W, Huberty G, Coats B, Harrison J, Klinman D, Poole S, Maier S, Johnson K, Chavez R, Watkins LR, Leinwand L, Milligan E.
Immunological priming potentiates non-viral anti-inflammatory gene therapy treatment of neuropathic pain.
Gene Ther. 2009.
50)  Klaschik S, Tross D, Klinman DM.
Inductive and suppressive networks regulate TLR9-dependent gene expression in vivo.
J. Leukoc. Biol. 2009.
51)  Klinman DM, Tross D, Klaschik S, Shirota H, Sato T.
Therapeutic applications and mechanisms underlying the activity of immunosuppressive oligonucleotides.
Ann. N. Y. Acad. Sci. 1175: 80-8, 2009.
52)  Yasuda H, Leelahavanichkul A, Tsunoda S, Dear JW, Takahashi Y, Ito S, Hu X, Zhou H, Doi K, Childs R, Klinman DM, Yuen PS, Star RA.
Chloroquine and inhibition of Toll-like receptor 9 protect from sepsis-induced acute kidney injury.
Am. J. Physiol. Renal Physiol. 294: F1050-8, 2008.
53)  Tross D, Klinman DM.
Effect of CpG oligonucleotides on vaccine-induced B cell memory.
J. Immunol. 181: 5785-90, 2008.
54)  Klinman D.
ELISPOT assay to detect cytokine-secreting murine and human cells.
Current protocols in immunology / edited by John E. Coligan ... [et al.]. Chapter 6: Unit 6.19, 2008.
55)  Sato T, Shimosato T, Alvord WG, Klinman DM.
Suppressive oligodeoxynucleotides inhibit silica-induced pulmonary inflammation.
J. Immunol. 180: 7648-54, 2008.
56)  Klinman D, Shirota H, Tross D, Sato T, Klaschik S.
Synthetic oligonucleotides as modulators of inflammation.
J. Leukoc. Biol. 84: 958-64, 2008.
57)  Zhu Q, Egelston C, Vivekanandhan A, Uematsu S, Akira S, Klinman DM, Belyakov IM, Berzofsky JA.
Toll-like receptor ligands synergize through distinct dendritic cell pathways to induce T cell responses: implications for vaccines.
Proc. Natl. Acad. Sci. U.S.A. 105: 16260-5, 2008.
58)  Fogg CN, Americo JL, Lustig S, Huggins JW, Smith SK, Damon I, Resch W, Earl PL, Klinman DM, Moss B.
Adjuvant-enhanced antibody responses to recombinant proteins correlates with protection of mice and monkeys to orthopoxvirus challenges.
Vaccine. 25: 2787-99, 2007.
59)  Saha S, Takeshita F, Matsuda T, Jounai N, Kobiyama K, Matsumoto T, Sasaki S, Yoshida A, Xin KQ, Klinman DM, Uematsu S, Ishii KJ, Akira S, Okuda K.
Blocking of the TLR5 activation domain hampers protective potential of flagellin DNA vaccine.
J. Immunol. 179: 1147-54, 2007.
60)  Klaschik S, Gursel I, Klinman DM.
CpG-mediated changes in gene expression in murine spleen cells identified by microarray analysis.
Mol. Immunol. 44: 1095-104, 2007.
61)  Shirota H, Petrenko L, Hong C, Klinman DM.
Potential of transfected muscle cells to contribute to DNA vaccine immunogenicity.
J. Immunol. 179: 329-36, 2007.
62)  Klinman DM, Currie D, Lee G, Grippe V, Merkel T.
Systemic but not mucosal immunity induced by AVA prevents inhalational anthrax.
Microbes Infect. 9: 1478-83, 2007.
63)  Klinman DM.
Adjuvant activity of CpG oligodeoxynucleotides.
Int. Rev. Immunol. 25: 135-54, 2006.
64)  Shirota H, Ishii KJ, Takakuwa H, Klinman DM.
Contribution of interferon-beta to the immune activation induced by double-stranded DNA.
Immunology. 118: 302-10, 2006.
65)  Klinman DM.
CpG oligonucleotides accelerate and boost the immune response elicited by AVA, the licensed anthrax vaccine.
Expert review of vaccines. 5: 365-9, 2006.
66)  Klinman DM, Xie H, Ivins BE.
CpG oligonucleotides improve the protective immune response induced by the licensed anthrax vaccine.
Ann. N. Y. Acad. Sci. 1082: 137-50, 2006.
67)  Gursel M, Gursel I, Mostowski HS, Klinman DM.
CXCL16 influences the nature and specificity of CpG-induced immune activation.
J. Immunol. 177: 1575-80, 2006.
68)  Saha S, Takeshita F, Sasaki S, Matsuda T, Tanaka T, Tozuka M, Takase K, Matsumoto T, Okuda K, Ishii N, Yamaguchi K, Klinman DM, Xin KQ, Okuda K.
Multivalent DNA vaccine protects mice against pulmonary infection caused by Pseudomonas aeruginosa.
Vaccine. 24: 6240-9, 2006.
69)  Fujimoto C, Yu CR, Shi G, Vistica BP, Wawrousek EF, Klinman DM, Chan CC, Egwuagu CE, Gery I.
Pertussis toxin is superior to TLR ligands in enhancing pathogenic autoimmunity, targeted at a neo-self antigen, by triggering robust expansion of Th1 cells and their cytokine production.
J. Immunol. 177: 6896-903, 2006.
70)  Takeshita F, Tanaka T, Matsuda T, Tozuka M, Kobiyama K, Saha S, Matsui K, Ishii KJ, Coban C, Akira S, Ishii N, Suzuki K, Klinman DM, Okuda K, Sasaki S.
Toll-like receptor adaptor molecules enhance DNA-raised adaptive immune responses against influenza and tumors through activation of innate immunity.
J. Virol. 80: 6218-24, 2006.
71)  Ito S, Ishii KJ, Ihata A, Klinman DM.
Contribution of nitric oxide to CpG-mediated protection against Listeria monocytogenes.
Infect. Immun. 73: 3803-5, 2005.
72)  Xie H, Gursel I, Ivins BE, Singh M, O'Hagan DT, Ulmer JB, Klinman DM.
CpG oligodeoxynucleotides adsorbed onto polylactide-co-glycolide microparticles improve the immunogenicity and protective activity of the licensed anthrax vaccine.
Infect. Immun. 73: 828-33, 2005.
73)  Ito S, Ishii KJ, Gursel M, Shirotra H, Ihata A, Klinman DM.
CpG oligodeoxynucleotides enhance neonatal resistance to Listeria infection.
J. Immunol. 174: 777-82, 2005.
74)  Ito S, Pedras-Vasconcelos J, Klinman DM.
CpG oligodeoxynucleotides increase the susceptibility of normal mice to infection by Candida albicans.
Infect. Immun. 73: 6154-6, 2005.
75)  Sugiyama T, Gursel M, Takeshita F, Coban C, Conover J, Kaisho T, Akira S, Klinman DM, Ishii KJ.
CpG RNA: identification of novel single-stranded RNA that stimulates human CD14+CD11c+ monocytes.
J. Immunol. 174: 2273-9, 2005.
76)  Ishii KJ, Ito S, Tamura T, Hemmi H, Conover J, Ozato K, Akira S, Klinman DM.
CpG-activated Thy1.2+ dendritic cells protect against lethal Listeria monocytogenes infection.
Eur. J. Immunol. 35: 2397-405, 2005.
77)  Coban C, Ishii KJ, Gursel M, Klinman DM, Kumar N.
Effect of plasmid backbone modification by different human CpG motifs on the immunogenicity of DNA vaccine vectors.
J. Leukoc. Biol. 78: 647-55, 2005.
78)  Dalloul RA, Lillehoj HS, Klinman DM, Ding X, Min W, Heckert RA, Lillehoj EP.
In ovo administration of CpG oligodeoxynucleotides and the recombinant microneme protein MIC2 protects against Eimeria infections.
Vaccine. 23: 3108-13, 2005.
79)  Xin KQ, Jounai N, Someya K, Honma K, Mizuguchi H, Naganawa S, Kitamura K, Hayakawa T, Saha S, Takeshita F, Okuda K, Honda M, Klinman DM, Okuda K.
Prime-boost vaccination with plasmid DNA and a chimeric adenovirus type 5 vector with type 35 fiber induces protective immunity against HIV.
Gene Ther. 12: 1769-77, 2005.
80)  Dong L, Ito S, Ishii KJ, Klinman DM.
Suppressive oligodeoxynucleotides delay the onset of glomerulonephritis and prolong survival in lupus-prone NZB x NZW mice.
Arthritis Rheum. 52: 651-8, 2005.
81)  Shirota H, Gursel I, Gursel M, Klinman DM.
Suppressive oligodeoxynucleotides protect mice from lethal endotoxic shock.
J. Immunol. 174: 4579-83, 2005.
82)  Lugo-Villarino G, Ito S, Klinman DM, Glimcher LH.
The adjuvant activity of CpG DNA requires T-bet expression in dendritic cells.
Proc. Natl. Acad. Sci. U.S.A. 102: 13248-53, 2005.
83)  Klinman DM, Gursel I, Klaschik S, Dong L, Currie D, Shirota H.
Therapeutic potential of oligonucleotides expressing immunosuppressive TTAGGG motifs.
Ann. N. Y. Acad. Sci. 1058: 87-95, 2005.
84)  Takeshita F, Ishii KJ, Kobiyama K, Kojima Y, Coban C, Sasaki S, Ishii N, Klinman DM, Okuda K, Akira S, Suzuki K.
TRAF4 acts as a silencer in TLR-mediated signaling through the association with TRAF6 and TRIF.
Eur. J. Immunol. 35: 2477-85, 2005.
85)  Sen G, Flora M, Chattopadhyay G, Klinman DM, Lees A, Mond JJ, Snapper CM.
The critical DNA flanking sequences of a CpG oligodeoxynucleotide, but not the 6 base CpG motif, can be replaced with RNA without quantitative or qualitative changes in Toll-like receptor 9-mediated activity.
Cell. Immunol. 232: 64-74, 2004.
86)  Verthelyi D, Ishii KJ, Gursel M, Takeshita F, Klinman DM.
Human peripheral blood cells differentially recognize and respond to two distinct CPG motifs.
J. Immunol. 166: 2372-7, 2001.
87)  Klinman DM, Yi AK, Beaucage SL, Conover J, Krieg AM.
CpG motifs present in bacteria DNA rapidly induce lymphocytes to secrete interleukin 6, interleukin 12, and interferon gamma.
Proc. Natl. Acad. Sci. U.S.A. 93: 2879-83, 1996.
88)  Krieg AM, Yi AK, Matson S, Waldschmidt TJ, Bishop GA, Teasdale R, Koretzky GA, Klinman DM.
CpG motifs in bacterial DNA trigger direct B-cell activation.
Nature. 374: 546-9, 1995.
89)  Klinman DM, Higgins KW, Conover J.
Sequential immunizations with rgp120s from independent isolates of human immunodeficiency virus type 1 induce the preferential expansion of broadly crossreactive B cells.
J. Exp. Med. 173: 881-7, 1991.
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This page was last updated on 8/4/2014.