Download 陶秘華 Mi-Hua Tao Institution Institute of Biomedical Sciences

陶秘華 Mi-Hua Tao
Institution
Institute of Biomedical Sciences, Academia Sinica
Title
Research Fellow
Tel
+886-2-26523078
Fax
+886-2-27829142
E-mail
[email protected]
128 Academia Rd., Sec. 2, IBMS, Academia Sinica, Taipei, Taiwan 11529
Address
EDUCATION AND POSITIONS：
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Postdoctoral fellow (Oncology) Stanford University, Palo Alto, with Dr. Ronald Levy.
(1990-1993)
Ph.D. (Microbiology/Immunology), Columbia University, New York, with Dr. Sherie L.
Morrison. (1985-1990)
 M.Ph. (Microbiology/Immunology), Columbia University, New York. (1986-1988)
 M.A. (Microbiology/Immunology), Columbia University, New York. (1985-1986)
 B.A. (Medical Technology), National Taiwan University, Taiwan. (1979-1983)
HONORS：
 2010: NIH, USA, R21 grant (subaward 09-000514-01-AS ), Award title “Immunotherapy of
murine primary biliary cirrhosis”, Prime Award: 1R21AI085022-01 (Leung, Patrick,
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University of California, Davis)
2003-05: Outstanding Research Award, National Science Council, Taiwan (國科會傑出研究
獎)
2001: ISI Citation Classic Award for “Most-Cited Papers” from 1981-1999 in Taiwan. ISI
Thomson Scientific and National Science Council, Taiwan. (台灣地區 1981-1999 年論文引用
次數最多獎). The awarded article is “Chow, Y. H., W. L. Huang, W. K. Chi, Y. D. Chu, &
M. H. Tao. (1997) Improvement of hepatitis B virus DNA vaccines by plasmids coexpressing
hepatitis B surface antigen and interleukin-2. J Virol 71: 169-178..
2000-01: Outstanding Research Award, National Science Council, Taiwan (國科會傑出研究
獎)

1999: Research Award for Junior Research Investigators, Academia Sinica, Taipei, Taiwan (中
央研究院年輕學者研究著作獎)

1991-93: Postdoctoral Fellowship, The Jane Coffin Childs Memorial Fund for Medical
Research, USA
1991-93: Fellowship in Cancer Research, Stanford University, USA
1986-90: Graduate Assistantship, Columbia University, USA
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SPECIALITY & RESEARCH FIELD OF INTEREST：
Hepatitis B Virus, Viral Immunology, Tumor Immunology, Cancer Gene Therapy and
Immunotherapy
RESEARCH INTERESTS (Maximum 500 words)：
Chronic hepatitis B virus (HBV) infection is a serious global health problem, leading to high
incidence of cirrhosis and hepatocellular carcinoma (HCC). In these patients, T cell responses to
HBV are usually weak and accompanied with various levels of T-cell dysfunctions. The research
focus of my laboratory is to understand mechanisms responsible for immune tolerance to HBV, and
to develop novel therapeutic strategies to treat chronic HBV and HBV-associated HCC. We
developed several HBV animal models, including HBV transgenic mice, human liver chimeric
mice, and mice transduced with HBV pseudoviruses, to address these questions. Using these animal
models, we investigate the roles of HBV antigenicity, liver microenvironment, and innate immunity
in establishing chronic HBV. We develop immune interventions by therapeutic vaccines and local
cytokine treatment to prevent or modify progression of chronic HBV and HCC. We also investigate
the therapeutic efficacy of adeno-associated virus-mediated RNA interference gene therapy in
HBV-infected human liver chimeric mice. Through these efforts, our long-term goal is to find a
cure for chronic HBV and HBV-associated HCC.
Publication (referred papers)
1.
Morrison, S. L., S. Canfield, S. Porter, L. K. Tan, M. H. Tao, & L. A. Wims. (1988)
2.
Production and characterization of genetically engineered antibody molecules. Clin
Chem 34: 1668-1675.
Tao, M. H. & S. L. Morrison. (1989) Studies of aglycosylated chimeric mouse-human
IgG. Role of carbohydrate in the structure and effector functions mediated by the
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human IgG constant region. J Immunol 143: 2595-2601.
Wright, A., M. H. Tao, E. A. Kabat, & S. L. Morrison. (1991) Antibody variable
region glycosylation: position effects on antigen binding and carbohydrate structure.
4.
Embo J 10: 2717-2723.
Perfetti, V., P. Borden, M. H. Tao, S. L. Morrison, & E. A. Kabat. (1991) Specificity
and variable region cDNA sequence of an isogeneic monoclonal antiidiotype to an
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anti-alpha(1----6)dextran. Mol Immunol 28: 505-515.
Artandi, S. E., S. M. Canfield, M. H. Tao, K. L. Calame, S. L. Morrison, & V. R.
Bonagura. (1991) Molecular analysis of IgM rheumatoid factor binding to chimeric
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IgG. J Immunol 146: 603-610.
Tao, M. H., S. M. Canfield, & S. L. Morrison. (1991) The differential ability of
human IgG1 and IgG4 to activate complement is determined by the COOH-terminal
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sequence of the CH2 domain. J Exp Med 173: 1025-1028.
Bonagura, V. R., S. E. Artandi, N. Agostino, M. H. Tao, & S. L. Morrison. (1992)
Mapping rheumatoid factor binding sites using genetically engineered, chimeric IgG
antibodies. DNA Cell Biol 11: 245-252.
8.
Tao, M. H., R. I. Smith, & S. L. Morrison. (1993) Structural features of human
immunoglobulin G that determine isotype-specific differences in complement
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10.
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activation. J Exp Med 178: 661-667.
Tao, M. H. & R. Levy. (1993) Idiotype/granulocyte-macrophage colony-stimulating
factor fusion protein as a vaccine for B-cell lymphoma [see comments]. Nature 362:
755-758.
Chen, T. T., M. H. Tao, & R. Levy. (1994) Idiotype-cytokine fusion proteins as
cancer vaccines. Relative efficacy of IL-2, IL-4, and granulocyte-macrophage
colony-stimulating factor. J Immunol 153: 4775-4787.
Phillips, M. L., M. H. Tao, S. L. Morrison, & V. N. Schumaker. (1994)
Human/mouse chimeric monoclonal antibodies with human IgG1, IgG2, IgG3 and
IgG4 constant domains: electron microscopic and hydrodynamic characterization.
12.
Mol Immunol 31: 1201-1210.
Nickerson, K. G., M. H. Tao, H. T. Chen, J. Larrick, & E. A. Kabat. (1995) Human
and mouse monoclonal antibodies to blood group A substance, which are nearly
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identical immunochemically, use radically different primary sequences. J Biol Chem
270: 12457-12465.
Hsu, C. H., K. Y. Chua, M. H. Tao, S. K. Huang, & K. H. Hsieh. (1996) Inhibition of
specific IgE response in vivo by allergen-gene transfer. Int Immunol 8: 1405-1411.
Hsu, C. H., K. Y. Chua, M. H. Tao, Y. L. Lai, H. D. Wu, S. K. Huang, & K. H. Hsieh.
(1996) Immunoprophylaxis of allergen-induced immunoglobulin E synthesis and
airway hyperresponsiveness in vivo by genetic immunization [see comments]. Nat
Med 2: 540-544.
Chow, Y. H., W. L. Huang, W. K. Chi, Y. D. Chu, & M. H. Tao. (1997)
Improvement of hepatitis B virus DNA vaccines by plasmids coexpressing hepatitis B
surface antigen and interleukin-2. J Virol 71: 169-178.
Chow, Y. H., B. L. Chiang, Y. L. Lee, W. K. Chi, W. C. Lin, Y. T. Chen, & M. H.
Tao. (1998) Development of Th1 and Th2 populations and the nature of immune
responses to hepatitis B virus DNA vaccines can be modulated by codelivery of
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various cytokine genes. J Immunol 160: 1320-1329.
Lee, Y. L., M. H. Tao, Y. H. Chow, & B. L. Chiang. (1998) Construction of vectors
expressing bioactive heterodimeric and single-chain murine interleukin-12 for gene
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therapy. Hum Gene Ther 9: 457-465.
Liu, S. J., Y. P. Sher, C. C. Ting, K. W. Liao, C. P. Yu, & M. H. Tao. (1998)
Treatment of B-cell lymphoma with chimeric IgG and single-chain Fv
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antibody-interleukin-2 fusion proteins. Blood 92: 2103-2112.
Tseng, Y. L., R. L. Hong, M. H. Tao, & F. H. Chang. (1999) Sterically stabilized
anti-idiotype immunoliposomes improve the therapeutic efficacy of doxorubicin in a
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murine B-cell lymphoma model. Int J Cancer 80: 723-730.
Chen, H. W., C. H. Pan, M. Y. Liau, R. Jou, C. J. Tsai, H. J. Wu, Y. L. Lin, & M. H.
Tao. (1999) Screening of protective antigens of Japanese encephalitis virus by DNA
immunization: a comparative study with conventional viral vaccines. J Virol 73:
10137-10145.
Pan, C. H., H. W. Chen, & M. H. Tao. (1999) Modulation of immune responses to
DNA vaccines by codelivery of cytokine genes. J Formos Med Assoc 98: 722-729.
Kovarik, J., X. Martinez, M. Pihlgren, P. Bozzotti, M. H. Tao, T. J. Kipps, T. F. Wild,
P. H. Lambert, & C. A. Siegrist. (2000) Limitation of in vivo IL-12 supplementation
strategies to induce Th1 life responses to model viral and bacterial vaccine antigens.
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Virology 268: 122-131.
Huang, Y. H., J. C. Wu, M. H. Tao, W. J. Syu, S. C. Hsu, W. K. Chi, F. Y. Chang, &
S. D. Lee. (2000) DNA-based immunization produces Th1 immune responses to
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hepatitis delta virus in a mouse model. Hepatology 32: 104-110
Huang, T. H., P. Y. Wu, C. N. Lee, H. I. Huang, S. L. Hsieh, J. Kung, & M. H. Tao
(2000) Enhanced antitumor immunity by fusion of CTLA-4 to a self tumor antigen.
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Blood (Plenary paper) 96: 3663-3670 .
Chen, H. W., C. H. Pan, H. W. Huang, M. Y. Liau, J. R. Chiang, & M. H. Tao. (2001)
Suppression of immune response and protective immunity to a Japanese encephalitis
virus DNA vaccine by coadministration of an IL-12-expressing plasmid. J. Immunol.
166: 7419-7426.
26.
Pan, C. H., H. W. Chen, H. W. Huang, & M. H. Tao. (2001) Protective mechanisms
induced by a Japanese encephalitis virus DNA vaccine: requirement for antibody but
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not CD8+ cytotoxic T cell responses. J. Virol. 75: 11457
Ou-Yang, P., L. H. Hwang, M. H. Tao, B. L. Chiang, & D. S. Chen (2002)
Co-delivery of GM-CSF gene enhances the immune response of hepatitis C viral core
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protein-expressing DNA vaccine: role of dendritic cells. J. Med. Virol. 66: 320-328.
Chen, H. W., H. I. Huang, Y. P. Lee, L. L. Chen, H. K. Liu, M. L. Cheng, J. P. Tsai,
M. H. Tao, & C. C. Ting (2002) Linkage of CD40L to a self-tumor antigen enhances
the antitumor immune responses of dendritic cell-based treatment. Cancer Immunol
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Immunother 51: 341 –348
Lee, S. C., C. J. Wu, P. Y. Wu, Y. L. Huang, C. W. Wu, & M. H. Tao. (2003)
Inhibition of estabhished subcutaneous and metastatic murine tumors by
intramuscular electroporation of the Interleukin 12 gene. J. Biomed. Sci. 10: 73-86
Chen, H. W., Y. P. Lee, Y. F. Chung, Y. C. Shih, J. P. Tsai, M. H. Tao, & C. C. Ting
(2003) Inducing long-term survival with lasting anti-tumor immunity in treating B
cell lymphoma by a combined dendritic cell-based and hydrodynamic
plasmid-encoding IL-12 gene therapy. Int Immunol 15: 427-435
31.
Lo, C. H., S. C. Lee, P. Y. Wu, W. Y. Pan, J. Su, C. W. Cheng, S. R. Roffler, B. L.
Chiang, C. N. Lee, C. W. Wu, & M. H. Tao. (2003) Antitumor and antimetastatic
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activity of Interleukin 23. J Immunol 171: 600-607.
Wu, C. J., H. W. Huang, & M. H. Tao. (2003) Induction of cross-protection against
two wild-type Taiwanese isolates of Japanese encephalitis virus using Beijing-1
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strain DNA vaccine. Vaccine 21: 3938-45
Huang, H. I., P. Y. Wu, C. Y. Teo, M. N. Chen, Y. C. Chen, & M. H. Tao. (2004)
Improved immunogenicity of a self tumor antigen by covalent linkage to CD40 ligand.
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Int J Cancer 108: 696-703
Wu, C. J., S. C. Lee, H. W. Huang, & M. H. Tao. (2004) In vivo electroporation of
skeletal muscles increases the efficacy of JEV DNA vaccine. Vaccine 22: 1457-1464
Ye, Y. L., Y. L. Lee, Z. J. Chuang, H. J. Lai, C. C. Chen, M. H. Tao, & B. L. Chiang.
(2004) Dendritic cells modulated by cytokine-expressing adenoviruses alleviate
eosinophilia and airway hyperresponsiveness in an animal model of asthma. J
Allergy Clin Immunol 114: 88-96
Lin, C. C., C. W. Chou, A. L. Shiau, C. F. Tu, T. M. Ko, Y. L. Chen, B. C. Yang, M.
H. Tao, & M. D. Lai. (2004) Therapeutic HER2/Neu DNA Vaccine Inhibits Mouse
Tumor Naturally Overexpressing Endogenous Neu. Mol Ther 10: 290-301
Huang, Y. H., M. H. Tao, C. P. Hu, W. J. Syu, & J. C. Wu. (2004) Identification of
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novel HLA-A*0201-restricted CD8+ T-cell epitopes on hepatitis delta virus. J Gen
Virol 85: 3089-98.
Shiau, Y. T., Y. H. Huang, J. C. Wu, M. H. Tao, W. Syu, Jr., F. Y. Chang, & S. D.
Lee. (2006) Analysis of humoral immunity of hepatitis D virus DNA vaccine
generated in mice by using different dosage, gene gun immunization, and in vivo
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electroporation. J Chin Med Assoc 69:7-13.
Chen, C. H., K. Y. Su, M. H. Tao, S. W. Lin, Y. H. Su, Y. C. Tsai, K. C. Cheng, Y.
M. Jeng, & J. C. Sheu. (2006) Decreased expressions of hepsin in human
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hepatocellular carcinomas. Liver Int 26: 774-80.
Kim, S. A., C. M. Liang, I. C. Cheng, Y. C. Cheng, M. T. Chiao, C. J. Tseng, F. Lee,
M. H. Jong, M. H. Tao, N. S. Yang, & S. M. Liang. (2006) DNA vaccination against
foot-and-mouth disease via electroporation: study of molecular approaches for
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enhancing VP1 antigenicity. J Gene Med 8: 1182-91.
Nie, Z., Y. K. Tzeng, H. C. Chang, C. C. Chiu, C. Y. Chang, C. M. Chang, & M. H.
Tao. (2006) Microscopy-Based Mass Measurement of a Single Whole Virus in a
Cylindrical Ion Trap. Angew Chem Int Ed 45: 8131-34.
Wu, C. J., T. L. Li, H. W. Huang, M. H. Tao, &Y. L. Chan. (2006) Development of
an effective Japanese encephalitis virus-specific DNA vaccine. Microbes Infect
8:2578-86
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Chen, C. C., T. M. Ko, H. I. Ma, H. L. Wu, X. Xiao, J. Li, C. M. Chang, P. Y. Wu, C.
H. Chen, J. M. Han, C. P. Yu, K. S. Jeng, C. P. Hu, & M. H. Tao*. (2007) Long-term
inhibition of hepatitis B virus in transgenic mice by double-stranded
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adeno-associated virus 8-delivered short hairpin RNA. Gene Ther 14:11-9.
Liou, W., Y. J. Sung, M. H. Tao, & S. J. Lo (2008) Morphogenesis of the hepatitis B
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virion and subviral particles in the liver of transgenic mice. J Biomed Sci 15:311-6
Chen, C. C., C. P. Sun, H. I. Ma, C. C. Fang, P. Y. Wu, X. Xiao, & M. T. Tao*.
(2009) Comparative study of anti-hepatitis B virus RNA interference by
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double-stranded adeno-associated virus serotypes 7, 8, and 9. Mol Ther 17:352-9.
Chuang, T. F., S. C. Lee, K. W. Liao, Y. W. Hsiao, C. H. Lo, B. L. Chiang, X. Z. Lin,
M. H. Tao*, & R. M. Chu. (2009) Electroporation-mediated IL-12 gene therapy in a
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canine cancer model. Int J Cancer 125:698-707. (*Co-corresponding author)
Chang, S. L., C. L. Chang, P. I. Huang, M. H. Tao, & W. C. Yang. (2009) Role of
Cybr, a cytohesin binder and regulator, in CD4(+) T-cell function and host immunity.
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Mol Immunol 46:3218-3223.
Chen, H. W., C. H. Leng, H. Y. Liu, W. F. Cheng, Y. W. Chang, P. Y. Wu, S. P. Lien,
T. Y. Huang, S. K. Chiang, M. H. Lin, M. H. Tao, P. Chong, S. J. Liu. (2009)
Identification of HLA-A11-restricted CTL epitopes derived from HPV type 18 using
DNA immunization. Cancer Biol Ther 8:2023-30.
Ho, M. Y., S. J. Leu, G. G. Sun, M. H. Tao, S. J. Tang & K. H. Sun (2009) IL-27
directly restrains lung tumorigenicity by suppressing cyclooxygenase-2-mediated
activities. J Immunol 183:6217-26.
Leung P. S., A. Dhirapong, P. Y. Wu, & M. H. Tao (2010) Gene therapy in
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autoimmune diseases: Challenges and opportunities. Autoimmun Rev 9:170-4.
Leung P. S., S. A. Shu, T. P. Kenny, P. Y. Wu, & M. H. Tao (2010) Development
and validation of gene therapies in autoimmune diseases: Epidemiology to animal
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models. Autoimmun Rev 9:A400-9.
Chang, C. M., C. H. Lo, Y. M. Shih, Y. Chen, P. Y. Wu, K. Tsuneyama, S. R. Roffler,
& M. H. Tao* (2010) Treatment of Hepatocellular Carcinoma by Adeno-associated
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Virus Encoding Interleukin-15 Superagonist. Human Gene Ther 21:611-21.
Lo, C. H., C. M. Chang, S. W. Tang, W. Y. Pan, C. C. Fang, Y. Chen, P. Y. Wu, K.
Y. Chen, H. I. Ma, X. Xiao, & M. H. Tao* (2010) Differential antitumor effect of
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interleukin 12 family cytokines on orthotopic hepatocellular carcinoma. J Gene Med
12:423-34
Li, Y. C., B. M. Chen, P. C. Wu, T. L. Cheng, L. S. Kao, M. H. Tao, A. Lieber, S. R.
Roffler. (2010) Cutting Edge: Mechanical Forces Acting on T Cells Immobilized via
the TCR Complex Can Trigger TCR Signaling. J Immunol 184:5959-63.
Kao, C. Y., C. N. Lin, I. S. Yu, M. H. Tao, H. L. Wu, G. Y. Shi, Y. L. Yang, J. T.
Kao & S. W. Lin. (2010) FIX-Triple, a gain-of-function factor IX variant, improves
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haemostasis in mouse models without increased risk of thrombosis. Thromb
Haemostasis 104:355-65.
Chou, H. Y., X. Z. Lin, W. Y. Pan, P. Y. Wu, C. M. Chang, T. Y. Lin, H. H. Shen &
M. H. Tao*. (2010) Hydrogel-Delivered GM-CSF Overcomes Nonresponsiveness to
Hepatitis B Vaccine through the Recruitment and Activation of Dendritic Cells. J
Immunol 185:5468-75.
Song, Y. C., A. H. Chou, A. Homhuan, M. H. Huang, S. K. Chiang, K. Y. Shen, P. W.
Chuang, C. H. Leng, M. H. Tao, P. Chong & S. Liu. (2011) Presentation of
lipopeptide by dendritic cells induces anti-tumor responses via an
endocytosis-independent pathway in vivo. J Leukoc Biol 90:323-32
Huang, Y. H., C. C. Fang, K. Tsuneyama, H. Y. Chou, W. Y. Pan, Y. M. Shih, P. Y.
Wu, Y. Chen, P. S. Leung, M. E. Gershwin & M. H. Tao*. (2011) A murine model of
hepatitis B-associated hepatocellular carcinoma generated by adeno-associated
virus-mediated gene delivery. Int J Oncol 39:1511-9
Ju, T.C., H. M. Chen, J. T. Lin, C. P. Chang, W. C. Chang, J. J. Kang, C. P. Sun, M.
H. Tao, P. H. Tu, C. Chang, D. W. Dickson, & Y. Chern. (2011) Nuclear
translocation of AMPK-alpha1 potentiates striatal neurodegeneration in
Huntington's disease. J Cell Biol 194:209-27
Chen, C. C., C. M. Chang, C. P. Sun, C. P. Yu, P. Y. Wu, K. S. Jeng, C. P. Hu, P. J.
Chen, J. C. Wu, C. Shih, M. E. Gershwin, & M. H. Tao*. (2012) Use of RNA
Interference to Modulate Liver Adenoma Development in A Murine Model
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Transgenic for Hepatitis B Virus. Gene Ther 19:25-33.
Pan, W. Y., C. H. Lo, C. C. Chen, P. Y. Wu, S. R. Roffler, S. K. Shyue, & M. H.
Tao*. (2012) Cancer immunotherapy using a membrane-bound interleukin 12 with
B7-1 transmembrane and cytoplasmic domains. Mol. Ther. 20:927-37
Hsu, Y. C., H. P. Huang, I. S. Yu, K. Y. Su, S. R. Lin, W. C. Lin, H. L. Wu, G. Y.
Shi, M. H. Tao, C. H. Kao, Y. M. Wu, P. E. Martin, S. Y. Lin, P. C. Yang, & S. W.
Lin. (2012) Serine protease hepsin regulates hepatocyte size and hemodynamic
retention of tumor cells via hepatocyte growth factor signaling. Hepatology
56:1913-23.
Huang, H. C., C. C. Chen, W.C. Chang, M. H. Tao & C. Huang. (2012) Entry of
hepatitis B virus into immortalized human primary hepatocytes by clathrin-dependent
endocytosis. J Virol 86:9443-53.
Lin, J. T., W. C. Chang, H. M. Chen, H. L. Lai, C. Y. Chen, M. T. Tao & Y. Chern.
(2013) Feedback regulation between protein kinase A and the proteasome system
worsens Huntington's disease. Mol Cell Biol 33:1073-84.
Chen, R. C., P. Naiyanetr, S. A. Shu, J. Wang, G. X. Yang, T. P. Kenny, K. C.
Guggenheim, J. D. Butler, C. Bowlus, M. H. Tao, M. J. Kurth, A. A. Ansari, M.
Kaplan, R. L. Coppel, A. Lleo, M. E. Gershwin & P. S. Leung. (2013)
Antimitochondrial antibody heterogeneity and the xenobiotic etiology of primary
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biliary cirrhosis. Hepatology 57:1498-508.
Sun, C. P., T. H. Wu, C. C. Chen, P. Y. Wu, Y. M. Shih, K. Tsuneyama & M. H.
Tao*. (2013) Studies of Efficacy and Liver Toxicity Associated With AAV-mediated
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RNA Interference. Human Gene Ther 24:739-50.
Kao, C. Y., S. J. Yang, M. H. Tao, Y. M. Jeng, I. S. Yu & S. W. Lin. (2013)
Incorporation of the factor IX Padua mutation into FIX-Triple improves clotting
activity in vitro and in vivo. Thromb Haemost 110:244-56.