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Dr. Tzyy-Choou Wu

M.D., Ph.D., M.P.H.
Categories

Cancer Immunology

Titles

Professor of Pathology, The Johns Hopkins University School of Medicine
Professor of Oncology, The Johns Hopkins University School of Medicine
Professor of Obstetrics and Gynecology, The Johns Hopkins University
School of Medicine
Professor of Molecular Microbiology and Immunology, The Johns Hopkins
University, Bloomberg School of Public Health
Research Director of Gynecologic Pathology
Pathologist, The Johns Hopkins Hospital

Schools\Degrees

M.D., National Taiwan University College of Medicine, Taipei, Taiwan Ph.D., Molecular Virology, The Johns Hopkins Bloomberg School of Public Health M.P.H., Epidemiology, The Johns Hopkins Bloomberg School of Public Health

Training

Resident, Anatomic Pathology, The Johns Hopkins Hospital
Fellow, Gynecologic Pathology, The Johns Hopkins University School of Medicine

Certifications

State of Maryland License American Board of Pathology Certification in Anatomic Pathology

Clinical Interests

Gynecological pathology
Melecular diagnosis for viral infections

Research Summary

Research Summary

 

Each year, approximately 500,000 women worldwide develop cervical cancer, and 200,000 women die from this cancer. We are currently developing vaccines and immunotherapeutic strategies for human papillomavirus (HPV)-related cervical cancer and are running a molecular immunology lab for the development of human immunological assays for viral infection.

 

Dr. T.-C. Wu’s research focus has been in the area of human papillomavirus (HPV) vaccine development. He has created a unique preclinical murine tumor model that expresses HPV-16 oncogenic proteins, E6 and E7, and simulates specific molecular events in the progression of HPV+ precancerous lesions (CIN 3) to invasive cancer. This preclinical tumor model has been widely used and tested by researchers worldwide for HPV vaccine development.
Dr. Wu has focused on identifying vaccine and immunotherapeutic approaches to enhance antigen processing and presentation by dendritic cells, including intracellular targeting and intercellular spreading strategies, for the purpose of prevention and treatment of cervical lesions and cancers. Intracellular targeting directs antigen to different subcellular locations to enhance antigen processing and presentation. Meanwhile, intercellular spreading facilitates the distribution of antigen to neighboring cells by taking advantage of unique intercellular transport properties, allowing for an increase in the amount of antigen presented to effector cells. Dr. Wu has created an innovative approach that combines both antigen-specific immunotherapy and anti-angiogenesis to treat HPV E7-expressing tumors.
The impressive preclinical data derived from these studies have led to several clinical trials that are either currently under way or will soon commence. The continued development of these strategies will facilitate the development of vaccines that generate a potent immune response and antitumor effect against cervical cancer. Dr. Wu is also actively involved with investigating mechanisms of immune evasion of tumors, identifying new tumor-specific antigens, and applying vaccine strategies to other cancer systems with characterized tumor-specific antigens.
 

Journal Citations

Hung, C.F.; Tsai, Y.C.; He, L.; Coukos, G.; Fodor, I.; Qin, L.; Levitsky, H.; Wu, T.C. Vaccinia virus preferentially infects and controls human and murine ovarian tumors in mice. Gene Ther. 2006 Aug 17.

Hung, C.F.; Yang, M.; Wu, T.C. Modifying professional antigen-presenting cells to enhance DNA vaccine potency. Methods in molecular medicine. 2006;127:199-220.

Pai, S.I.; Lin, Y.Y.; Macaes, B.; Meneshian, A.; Hung, C.F.; Wu, T.C. Prospects of RNA interference therapy for cancer. Gene Ther. 2006 Mar;13(6):464-477.

Peng, S.; Tomson, T.T.; Trimble, C.; He, L.; Hung, C.F.; Wu, T.C. A combination of DNA vaccines targeting human papillomavirus type 16 E6 and E7 generates potent antitumor effects. Gene Ther. 2006 Feb;13(3):257-265.

Peng, S.; Trimble, C.; He, L.; Tsai, Y.C.; Lin, C.T.; Boyd, D.A.; Pardoll, D.; Hung, C.F.; Wu, T.C. Characterization of HLA-A2-restricted HPV-16 E7-specific CD8(+) T-cell immune responses induced by DNA vaccines in HLA-A2 transgenic mice. Gene Ther. 2006 Jan;13(1):67-77.

Roden, R.; Wu, T.C. How will HPV vaccines affect cervical cancer? Nat Rev Cancer. 2006 Oct;6(10):753-763.

Chang, C.L.; Tsai, Y.C.; He, L.; Wu, T.C.; Hung, C.F. Cancer immunotherapy using irradiated tumor cells secreting heat shock protein 70. Cancer Res. 2007 Oct 15;67(20):10047-10057.

Chang, C.L.; Wu, T.C.; Hung, C.F. Control of human mesothelin-expressing tumors by DNA vaccines. Gene Ther. 2007 Aug;14(16):1189-1198.

Huang, B.; Mao, C.P.; Peng, S.; He, L.; Hung, C.F.; Wu, T.C. Intradermal administration of DNA vaccines combining a strategy to bypass antigen processing with a strategy to prolong dendritic cell survival enhances DNA vaccine potency. Vaccine. 2007 Nov 7;25(45):7824-7831.

Hung, C.F.; Calizo, R.; Tsai, Y.C.; He, L.; Wu, T.C. A DNA vaccine encoding a single-chain trimer of HLA-A2 linked to human mesothelin peptide generates anti-tumor effects against human mesothelin-expressing tumors. Vaccine. 2007 Jan 2;25(1):127-135.

Hung, C.F.; Tsai, Y.C.; He, L.; Coukos, G.; Fodor, I.; Qin, L.; Levitsky, H.; Wu, T.C. Vaccinia virus preferentially infects and controls human and murine ovarian tumors in mice. Gene Ther. 2007 Jan;14(1):20-29.

Hung, C.F.; Tsai, Y.C.; He, L.; Wu, T.C. Control of mesothelin-expressing ovarian cancer using adoptive transfer of mesothelin peptide-specific CD8+ T cells. Gene Ther. 2007 Jun;14(12):921-929.

Hung, C.F.; Tsai, Y.C.; He, L.; Wu, T.C. DNA vaccines encoding Ii-PADRE generates potent PADRE-specific CD4+ T-cell immune responses and enhances vaccine potency. Mol Ther. 2007 Jun;15(6):1211-1219.

Kim, D.; Hoory, T.; Wu, T.C.; Hung, C.F. Enhancing DNA vaccine potency by combining a strategy to prolong dendritic cell life and intracellular targeting strategies with a strategy to boost CD4+ T cell. Hum Gene Ther. 2007 Nov;18(11):1129-1139.

Kim, D.; Hung, C.F.; Wu, T.C. Monitoring the trafficking of adoptively transferred antigen- specific CD8-positive T cells in vivo, using noninvasive luminescence imaging. Hum Gene Ther. 2007 Jul;18(7):575-588.

Lin, K.Y.; Lu, D.; Hung, C.F.; Peng, S.; Huang, L.; Jie, C.; Murillo, F.; Rowley, J.; Tsai, Y.C.; He, L.; Kim, D.J.; Jaffee, E.; Pardoll, D.; Wu, T.C. Ectopic expression of vascular cell adhesion molecule-1 as a new mechanism for tumor immune evasion. Cancer Res. 2007 Feb 15;67(4):1832-1841.

Lin, Y.Y.; Alphs, H.; Hung, C.F.; Roden, R.B.; Wu, T.C. Vaccines against human papillomavirus. Front Biosci. 2007;12:246-264.

Mao, C.P.; Hung, C.F.; Wu, T.C. Immunotherapeutic strategies employing RNA interference technology for the control of cancers. J Biomed Sci. 2007 Nov 14;14:15-29.

Mao, C.P.; Lin, Y.Y.; Hung, C.F.; Wu, T.C. Immunological research using RNA interference technology. Immunology. 2007 Jul;121(3):295-307.

Monie, A.; Hung, C.F.; Wu, T.C. Preventive and therapeutic HPV vaccines. Curr Opin Investig Drugs. 2007 Dec;8(12):1038-1050.

Peng, S.; Trimble, C.; Wu, L.; Pardoll, D.; Roden, R.; Hung, C.F.; Wu, T.C. HLA-DQB1*02-restricted HPV-16 E7 peptide-specific CD4+ T-cell immune responses correlate with regression of HPV-16-associated high-grade squamous intraepithelial lesions. Clin Cancer Res. 2007 Apr 15;13(8):2479-2487.

Roden, R.B.; Monie, A.; Wu, T.C. Opportunities to improve the prevention and treatment of cervical cancer. Current molecular medicine. 2007 Aug;7(5):490-503.

Wu, T.C. The role of vascular cell adhesion molecule-1 in tumor immune evasion. Cancer Res. 2007 Jul 1;67(13):6003-6006.

Wu, T.C. Therapeutic human papillomavirus DNA vaccination strategies to control cervical cancer. Eur J Immunol. 2007 Feb;37(2):310-314.

Chaudhary, P.; Nicholas, J. Molecular biology of human herpesvirus-8 transformation. In: Nicholas, J.; Wu, T.-C.; Jeang, K.-T., editors, Human Cancer Viruses: Principles of Transformation and Pathogenesis: Karger; 2008. p. 186-210.

Hoory, T.; Monie, A.; Gravitt, P.; Wu, T.C. Molecular epidemiology of human papillomavirus. J Formos Med Assoc. 2008 Mar;107(3):198-217.

Huang, B.; Mao, C.P.; Peng, S.; Hung, C.F.; Wu, T.C. RNA interference-mediated in vivo silencing of fas ligand as a strategy for the enhancement of DNA vaccine potency. Hum Gene Ther. 2008 Aug;19(8):763-773.

Hung, C.F.; Ma, B.; Monie, A.; Tsen, S.W.; Wu, T.C. Therapeutic human papillomavirus vaccines: current clinical trials and future directions. Expert opinion on biological therapy. 2008 Apr;8(4):421-439.

Hung, C.F.; Wu, T.C.; Monie, A.; Roden, R. Antigen-specific immunotherapy of cervical and ovarian cancer. Immunol Rev. 2008 Apr;222:43-69.

Kim, D.; Gambhira, R.; Karanam, B.; Monie, A.; Hung, C.F.; Roden, R.; Wu, T.C. Generation and characterization of a preventive and therapeutic HPV DNA vaccine. Vaccine. 2008 Jan 17;26(3):351-360.

Kim, D.; Hoory, T.; Monie, A.; Ting, J.P.; Hung, C.F.; Wu, T.C. Enhancement of DNA vaccine potency through coadministration of CIITA DNA with DNA vaccines via gene gun. J Immunol. 2008 May 15;180(10):7019-7027.

Kim, D.; Monie, A.; He, L.; Tsai, Y.C.; Hung, C.F.; Wu, T.C. Role of IL-2 secreted by PADRE-specific CD4+ T cells in enhancing E7-specific CD8+ T-cell immune responses. Gene Ther. 2008 May;15(9):677-687.

Kim, D.; Monie, A.; Tsai, Y.C.; He, L.; Wang, M.C.; Hung, C.F.; Wu, T.C. Enhancement of CD4+ T-cell help reverses the doxorubicin-induced suppression of antigen-specific immune responses in vaccinated mice. Gene Ther. 2008 Aug;15(16):1176-1183.

Kurman, R.J.; Visvanathan, K.; Roden, R.; Wu, T.C.; Shih Ie, M. Early detection and treatment of ovarian cancer: shifting from early stage to minimal volume of disease based on a new model of carcinogenesis. Am J Obstet Gynecol. 2008 Apr;198(4):351-356.

Martin, H.J.; Hayward, S.D. The biology and molecular biology underlying Epstein-Barr virus oncogenesis. In: Nicholas, J.; Jeang, K.-T.; Wu, T.-C., editors, Human Cancer Viruses: Principles of Transformation and Pathogenesis: Karger; 2008. p. 150-169.

Park, Y.S.; Lee, J.H.; Hung, C.F.; Wu, T.C.; Kim, T.W. Enhancement of antibody responses to Bacillus anthracis protective antigen domain IV by use of calreticulin as a chimeric molecular adjuvant. Infect Immun. 2008 May;76(5):1952-1959.

Peng, S.; Trimble, C.; Alvarez, R.D.; Huh, W.K.; Lin, Z.; Monie, A.; Hung, C.F.; Wu, T.C. Cluster intradermal DNA vaccination rapidly induces E7-specific CD8+ T-cell immune responses leading to therapeutic antitumor effects. Gene Ther. 2008 Aug;15(16):1156-1166.

Roden, R.B.; Gravitt, P.; Wu, T.C. Towards global prevention of human papillomavirus-induced cancer. Eur J Immunol. 2008 Feb;38(2):323-326.

Rowley, J.; Monie, A.; Hung, C.F.; Wu, T.C. Inhibition of tumor growth by NK1.1+ cells and CD8+ T cells activated by IL-15 through receptor beta/common gamma signaling in trans. J Immunol. 2008 Dec 15;181(12):8237-8247.

Shi, C.; Parker, A.R.; Hua, L.; Morrell, C.N.; Lee, S.C.; Bandaru, V.; Dumler, J.S.; Wu, T.C.; Eshleman, J.R. Anti-gene padlocks eliminate Escherichia coli based on their genotype. The Journal of antimicrobial chemotherapy. 2008 Feb;61(2):262-272.

Tseng, C.W.; Hung, C.F.; Alvarez, R.D.; Trimble, C.; Huh, W.K.; Kim, D.; Chuang, C.M.; Lin, C.T.; Tsai, Y.C.; He, L.; Monie, A.; Wu, T.C. Pretreatment with cisplatin enhances E7-specific CD8+ T-Cell-mediated antitumor immunity induced by DNA vaccination. Clin Cancer Res. 2008 May 15;14(10):3185-3192.

Tseng, C.W.; Monie, A.; Trimble, C.; Alvarez, R.D.; Huh, W.K.; Buchsbaum, D.J.; Straughn, J.M., Jr.; Wang, M.C.; Yagita, H.; Hung, C.F.; Wu, T.C. Combination of treatment with death receptor 5-specific antibody with therapeutic HPV DNA vaccination generates enhanced therapeutic anti-tumor effects. Vaccine. 2008 Aug 12;26(34):4314-4319.

Tseng, C.W.; Monie, A.; Wu, C.Y.; Huang, B.; Wang, M.C.; Hung, C.F.; Wu, T.C. Treatment with proteasome inhibitor bortezomib enhances antigen-specific CD8+ T-cell-mediated antitumor immunity induced by DNA vaccination. J Mol Med. 2008 Aug;86(8):899-908.

Tseng, C.W.; Trimble, C.; Zeng, Q.; Monie, A.; Alvarez, R.D.; Huh, W.K.; Hoory, T.; Wang, M.C.; Hung, C.F.; Wu, T.C. Low-dose radiation enhances therapeutic HPV DNA vaccination in tumor-bearing hosts. Cancer Immunol Immunother. 2008 Sep 25.

van Zeeburg, H.J.; Snijders, P.J.; Wu, T.; Gluckman, E.; Soulier, J.; Surralles, J.; Castella, M.; van der Wal, J.E.; Wennerberg, J.; Califano, J.; Velleuer, E.; Dietrich, R.; Ebell, W.; Bloemena, E.; Joenje, H.; Leemans, C.R.; Brakenhoff, R.H. Clinical and molecular characteristics of squamous cell carcinomas from Fanconi anemia patients. J Natl Cancer Inst. 2008 Nov 19;100(22):1649-1653.

Best, S.R.; Peng, S.; Juang, C.M.; Hung, C.F.; Hannaman, D.; Saunders, J.R.; Wu, T.C.; Pai, S.I. Administration of HPV DNA vaccine via electroporation elicits the strongest CD8+ T cell immune responses compared to intramuscular injection and intradermal gene gun delivery. Vaccine. 2009 Sep 4;27(40):5450-5459.

Chang, C.L.; Ma, B.; Pang, X.; Wu, T.C.; Hung, C.F. Treatment with cyclooxygenase-2 inhibitors enables repeated administration of vaccinia virus for control of ovarian cancer. Mol Ther. 2009 Aug;17(8):1365-1372.
Kang, T.H.; Chung, J.Y.; Monie, A.; Pai, S.I.; Hung, C.F.; Wu, T.C. Enhancing DNA vaccine potency by co-administration of xenogenic MHC class-I DNA. Gene Ther. 2009 Nov 26;17:167-171.

Monie, A.; Tsen, S.W.; Hung, C.F.; Wu, T.C. Therapeutic HPV DNA vaccines. Expert Rev Vaccines. 2009 Sep;8(9):1221-1235.

Noh, K.H.; Kang, T.H.; Kim, J.H.; Pai, S.I.; Lin, K.Y.; Hung, C.F.; Wu, T.C.; Kim, T.W. Activation of Akt as a mechanism for tumor immune evasion. Mol Ther. 2009 Mar;17(3):439-447.

Rowley, J.; Monie, A.; Hung, C.F.; Wu, T.C. Expression of IL-15RA or an IL-15/IL-15RA fusion on CD8+ T cells modifies adoptively transferred T-cell function in cis. Eur J Immunol. 2009 Feb;39(2):491-506.

Trimble, C.L.; Peng, S.; Kos, F.; Gravitt, P.; Viscidi, R.; Sugar, E.; Pardoll, D.; Wu, T.C. A phase I trial of a human papillomavirus DNA vaccine for HPV16+ cervical intraepithelial neoplasia 2/3. Clin Cancer Res. 2009 Jan 1;15(1):361-367.

Trimble, C.L.; Peng, S.; Thoburn, C.; Kos, F.; Wu, T.C. Naturally occurring systemic immune responses to HPV antigens do not predict regression of CIN2/3. Cancer Immunol Immunother. 2009 Dec 13.

Tsen, S.W.; Wu, C.Y.; Meneshian, A.; Pai, S.I.; Hung, C.F.; Wu, T.C. Femtosecond laser treatment enhances DNA transfection efficiency in vivo. J Biomed Sci. 2009;16:36.

Tseng, C.W.; Trimble, C.; Zeng, Q.; Monie, A.; Alvarez, R.D.; Huh, W.K.; Hoory, T.; Wang, M.C.; Hung, C.F.; Wu, T.C. Low-dose radiation enhances therapeutic HPV DNA vaccination in tumor-bearing hosts. Cancer Immunol Immunother. 2009 May;58(5):737-748.

Chuang, C.M.; Monie, A.; Hung, C.F.; Wu, T.C. Treatment with imiquimod enhances antitumor immunity induced by therapeutic HPV DNA vaccination. J Biomed Sci. 2010;17:32.

Kang, T.H.; Chung, J.Y.; Monie, A.; Pai, S.I.; Hung, C.F.; Wu, T.C. Enhancing DNA vaccine potency by co-administration of xenogenic MHC class-I DNA. Gene Ther. 2010 Apr;17(4):531-540.

Kang, T.H.; Noh, K.H.; Kim, J.H.; Bae, H.C.; Lin, K.Y.; Monie, A.; Pai, S.I.; Hung, C.F.; Wu, T.C.; Kim, T.W. Ectopic expression of X-linked lymphocyte-regulated protein pM1 renders tumor cells resistant to antitumor immunity. Cancer Res. 2010 Apr 15;70(8):3062-3070.

Kim, D.; Hung, C.F.; Wu, T.C.; Park, Y.M. DNA vaccine with alpha-galactosylceramide at prime phase enhances anti-tumor immunity after boosting with antigen-expressing dendritic cells. Vaccine. 2010 Oct 21;28(45):7297-7305.

Lin, K.; Doolan, K.; Hung, C.F.; Wu, T.C. Perspectives for preventive and therapeutic HPV vaccines. J Formos Med Assoc. 2010 Jan;109(1):4-24.

Lin, K.; Roosinovich, E.; Ma, B.; Hung, C.F.; Wu, T.C. Therapeutic HPV DNA vaccines. Immunol Res. 2010 Jul;47(1-3):86-112.

Ma, B.; Roden, R.; Wu, T.C. Current status of human papillomavirus vaccines. J Formos Med Assoc. 2010 Jul;109(7):481-483.

Mao, C.P.; Hung, C.F.; Kang, T.H.; He, L.; Tsai, Y.C.; Wu, C.Y.; Wu, T.C. Combined administration with DNA encoding vesicular stomatitis virus G protein enhances DNA vaccine potency. J Virol. 2010 Mar;84(5):2331-2339.

Mao, C.P.; Wu, T.C. Inhibitory RNA molecules in immunotherapy for cancer. Methods Mol Biol. 2010;623:325-339.

Peng, S.; Best, S.R.; Hung, C.F.; Loyo, M.; Lyford-Pike, S.; Flint, P.W.; Tunkel, D.E.; Saunders, J.R.; Wu, T.C.; Pai, S.I. Characterization of human papillomavirus type 11-specific immune responses in a preclinical model. Laryngoscope. 2010 Mar;120(3):504-510.

Peng, S.; Monie, A.; Kang, T.H.; Hung, C.F.; Roden, R.; Wu, T.C. Efficient delivery of DNA vaccines using human papillomavirus pseudovirions. Gene Ther. 2010 Dec;17(12):1453-1464.

Su, J.H.; Wu, A.; Scotney, E.; Ma, B.; Monie, A.; Hung, C.F.; Wu, T.C. Immunotherapy for cervical cancer: Research status and clinical potential. BioDrugs. 2010 Apr 1;24(2):109-129.

Trimble, C.L.; Peng, S.; Thoburn, C.; Kos, F.; Wu, T.C. Naturally occurring systemic immune responses to HPV antigens do not predict regression of CIN2/3. Cancer Immunol Immunother. 2010 May;59(5):799-803.

Wu, C.Y.; Monie, A.; Pang, X.; Hung, C.F.; Wu, T.C. Improving therapeutic HPV peptide-based vaccine potency by enhancing CD4+ T help and dendritic cell activation. J Biomed Sci. 2010;17:88.

Zeng, Q.; Peng, S.; Monie, A.; Yang, M.; Pang, X.; Hung, C.F.; Wu, T.C. Control of Cervicovaginal HPV-16 E7-Expressing Tumors by the Combination of Therapeutic HPV Vaccination and Vascular Disrupting Agents. Hum Gene Ther. 2010 Dec 3.

Zhang, Y.Q.; Tsai, Y.C.; Monie, A.; Hung, C.F.; Wu, T.C. Carrageenan as an adjuvant to enhance peptide-based vaccine potency. Vaccine. 2010 Jul 19;28(32):5212-5219.

Zhang, Y.Q.; Tsai, Y.C.; Monie, A.; Wu, T.C.; Hung, C.F. Enhancing the therapeutic effect against ovarian cancer through a combination of viral oncolysis and antigen-specific immunotherapy. Mol Ther. 2010 Apr;18(4):692-699.

Kang, T.H.; Monie, A.; Wu, L.S.; Pang, X.; Hung, C.F.; Wu, T.C. Enhancement of protein vaccine potency by in vivo electroporation mediated intramuscular injection. Vaccine. 2011 Jan 29;29(5):1082-1089.

 

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