Principal Investigator/Program Director (Last, First, Middle):
Hung, Mien-Chie
BIOGRAPHICAL SKETCH
Provide the following information for the key personnel and other significant contributors in the order listed on Form
Page 2.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME
POSITION TITLE
MIEN-CHIE HUNG
PROFESSOR AND CHAIR
eRA COMMONS USER NAME
mhung@mdanderson.org
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as
nursing, and include postdoctoral training.)
DEGREE
INSTITUTION AND LOCATION
(if
YEAR(s)
FIELD OF STUDY
applicable)
NATIONAL TAIWAN UNIVERSITY, TAIWAN
B.S
1973
CHEMISTRY
NATIONAL TAIWAN UNIVERSITY, TAIWAN
M.S.
1977
BIOCHEMISTRY
BRANDEIS UNIVERSITY, MASSACHUSETTS
PH.D.
1983
BIOCHEMISTRY
WHITEHEAD INSTITUTE, MIT, MASS.
POSTDOC
1984-86
ONCOGENE
Mien-Chie Hung, Ph.D. is the Vice President for Basic Research, Ruth Leggett Jones Distinguished Chair,
Distinguished Teaching Professor, and Professor and Chair of the Department of Molecular and Cellular
Oncology at the University of Texas M. D. Anderson Cancer Center, Houston, Texas. He received his
undergraduate and graduate degrees from the National Taiwan University in Taiwan and his Ph.D. from
Brandeis University in Massachusetts. He was also trained as a postdoctoral fellow in Whitehead Institute/MIT.
Dr. Hung is a basic scientist with a translational vision. Since he became an independent researcher in 1986,
his laboratory has been well funded by extramural funding agencies including NIH and DOD. Currently, he is a
Principal Investigator for 1 PO1, 1RO1 and 1 DOD BCRP. In addition, Dr. Hung is a Project Leader for two
MDACC Specialized Programs of Research Excellence (SPOREs) in Breast (also a Co-PI), and Ovarian Cancer
and Program Leader for MDACC CCSG “Cell Biology and Signal Transduction” program. In 2008 (till present),
he was appointed as the Director of Center for Biological Pathways at the MDACC to coordinate biological
pathway studies in cancers through entire institution (the Center for Biological Pathways has amassed more
than 130 faculty members from 42 departments). Dr. Hung is one of the first three to clone functional
HER2/neu oncogene (PNAS, 1986; Science, 1985; Nature, 1986) of which over-expression/amplification is
known to be a poor prognostic marker for many human cancers. HER2/neu has been a successful therapeutic
target for development of novel targeted therapy. Dr. Hung is internationally recognized for his work on signaling
transduction pathways of tyrosine kinase growth factor receptors, such as epidermal growth factor receptor
(EGFR) and HER-2/neu, and molecular mechanisms of oncogenes, including transformation and tumorigenesis.
His group made a critical breakthrough in showing that the transmembrane tyrosine kinase receptor EGFR can
translocate into the nucleus from the cell surface to stimulate cell proliferation and to induce resistance to anticancer therapy. This paradigm-shift concept revolutionizes cell biology of receptor tyrosine kinase and paves a
novel avenue for designing next generation of anti-cancer therapy. Most recently, Dr. Hung’s group revealed a
novel mechanism that could link inflammation, obesity, diabetes and cancer, which provides a new way to
develop obesity-induced cancer and diabetes. Dr. Hung’s laboratory has had a long commitment to developing
effective gene therapy for breast, ovarian and pancreatic cancers, by identifying genes suitable for cancer
therapy (E1A and BIKDD), developing gene delivery systems (cationic and neutral liposomes) and designing
cancer-specific expression vectors, which enhance therapeutic efficacy and reduce any potential side effect
during commonly used therapies. Dr. Hung was the first to show that the adenovirus type 5 E1A gene has
antitumor activity in HER2/neu-overexpressing cancer cells in 1992, contrary to the originally and widely held
belief that was an oncogene. Studies on E1A as an anti-cancer gene have received national and international
acclaim. In 1996, Dr. Hung collaborated Dr. Hortoabgyi to bring the E1A gene into the first ever gene therapy
trial for breast and ovarian cancer. Since then, multiple trials for E1A gene therapy in breast, osteosarcoma,
ovarian and head and neck cancers have been completed (Clin Cancer Res 10:2986, 2004, Head Neck
24:661, 2002, Human Gene Ther 12:1591, 2001, Clin Cancer Res 7:1237, 2001 and J Clin Oncol 19:3422,
2001). He also developed a pancreatic cancer-specific expression vector to drive a potent mutant Bik gene,
which is in process of moving into human clinical trials soon with his clinical colleagues. In addition to
PHS 398/2590 (Rev. 09/04)
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Principal Investigator/Program Director (Last, First, Middle):
Hung, Mien-Chie
publishing more than 300 peer-reviewed papers, he has served many study sections of the NIH and various
funding agencies in many other countries to select awardees. These include Cancer Research of the UK,
Wellcome Trust of the UK, Austrian Science Fund (RWF), Israel Science Foundation, Italian Association for
Cancer Research, Academia Sinica of Taiwan and National Science Foundation of the USA. Dr. Hung also
serves as an editorial member for many journals in cancer research to evaluate quality of submission. Notable,
he is one of the founding Editorial Members for Cancer Cell, as well as an Associate Editor for Cancer
Research, Clinical Cancer Research, Molecular Cancer Research and Molecular Carcinogenesis. Dr. Hung
was inducted as an Academician of the Academia Sinica in Taiwan and a Member of the University of Texas
Academy of Health Science Education in 2002 and 2006, respectively. Very recently, he was selected as a Full
Member of Scientific Advisory Council, Susan G. Komen for the Cure.
Positions and Honors:
Professional Experience:
1977-1978 Assistant Research Fellow, Institute of Biological Chemistry, Academia Sinica, R.O.C.
1978 -1983 Predoctoral Fellow, Department of Biochemistry, Brandeis University, Gillette Graduate Teaching
Fellowship
1984-1986 Postdoctoral Fellow, Whitehead Institute/MIT, Postdoctoral fellowship from Cancer Research
Institute
1986-1991 Assistant Professor, Department of Tumor Biology, The University of Texas M.D. Anderson
Cancer Center
09/91-08/94 Associate Professor, Department of Tumor Biology, The University of Texas M.D. Anderson
Cancer Center
09/94Professor, The University of Texas M.D. Anderson Cancer Center
01/96-09/98 Deputy Chairman (ad interim), Dept. of Tumor Biology, U.T. M.D. Anderson Cancer Center
01/96Director, Breast Cancer Basic Research Program, U.T. M.D. Anderson Cancer Center
01/96-04/99 Hubert L. and Olive Stringer Endowed Professorship, U.T. M.D. Anderson Cancer Center
9/98-12/99 Chief, Section of Molecular Cell Biology, Dept. of Cancer Biology, U.T.M.D. Anderson Cancer
Center
5/99-02/00 Hubert L. and Olive Stringer Distinguished Professorship in Cancer Research, U.T. M. D.
Anderson Cancer Center
12/99-02/00 Chair (Ad interim), Department of Molecular and Cellular Oncology, U.T. M D. Anderson Cancer
Center
03/00-12/02 Ruth Legett Jones Chair, Department of Molecular and Cellular Oncology, U.T M. D. Anderson
Cancer Center
03/00Chair, Department of Molecular and Cellular Oncology, U.T. M. D. Anderson Cancer Center
01/03Ruth Legett Jones Distinguished Chair
09/08Director, Center for Biological Pathways, MDACC.
03-10Vice President for Basic Research, MDACC
Honors and Awards:
1989-98 John P. McGovern Outstanding Teacher Award U.T. H.S.C. -Houston (unprecedented three time
awardee in 1989, 1992, 1998).
1993
Faculty Achievement Award in Education (1993) and in Basic Research (1998), UTMDACC
1996
Member, Pathology B Study Section (1996 – 2000) and Sub-committee C (2001-2005), NIH.
Editorial Board, Clinical Cancer Research (1999–), Cancer Cell (2001-) and Cancer Research (2002-).
2002
Academician of the Academia Sinica, Taiwan
2006
Member, The University of Texas Academy of Health Science Education.
2007
Distinguished Teaching Professor, The University of Texas M. D. Anderson Cancer Center.
2010
Full Member, Scientific Advisory Council, Susan G. Komen for the Cure
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Principal Investigator/Program Director (Last, First, Middle):
Hung, Mien-Chie
Peer-reviewed publications
Dr. Mien-Chie Hung’s selected publications (from 329 peer-reviewed publications) in Cell-Nature-Science
series, from 2000 – present (listed in corresponding author only).
1. Xing, X., Wang, S-C., , Xia, W.Y., Zou, Y., Shao, R., Kwong, K.Y., Yu, Z., Zhang, S., Miller, S., Huang, L.,
and Hung, M.-C.
The Ets protein PEA3 suppresses HER-2/neu overexpression and inhibits
tumorigenesis. Nature Medicine 6:189-195, 2000. Citation: 111.
2. Lin, S.Y., Makino, K., Xia, W., Matin, A., Wen, Y., Kwong, K.Y., Bourguignon, L., and Hung, M.-C. Nuclear
localization of EGF receptor and its potential new role as a transcription factor. Nature Cell Biology 3:803808, 2001.
3. Zhou, B.P., Liao, Y., Xia, W., Spohn, B., Lee, M.H., and Hung, M.-C. Cytoplasmic localization of
p21Cip1/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells. Nature Cell Biology
3(3):245-252, 2001.
4. Zhou, B.P., Liao, Y., Xia, W., Zou, Y., Spohn, B., and Hung, M.-C. HER-2/neu induces ubiquitination via
Akt-mediated MDM2 phosphorylation. Nature Cell Biol. 3:973-982, 2001.
5. Bourguignon, L., Lan, K-H., Singleton, P., Lin, S-Y., Yu, D-H. and Hung, M-C. Localizing the EGF
receptor-Reply. Nature Cell Biology 4:E22-23, 2002.
6. Deng, J., Miller, S. A., Wang, H.-Y., Xia, W., Wen, Y., Zhou, B., Lin, S.-Y., Li, Yan and Hung, M.-C. Catenin interacts with and inhibits NF-B in human colon and breast cancers. Cancer Cell 2: 323334,2002
7. Hu, M.C-T, Lee, D.-F., Xia, W., Golfman, L., Ou-Yang, F., Yang, J.-Y., Zou, Y., Bao, S, Hanada, N., Saso,
H., Kobayashi R. and Hung, M-C. IkB kinase promotes tumourigenesis through inhibition of Forkhead
transcription factor FOXO3a. Cell 117:225-237, 2004.
8. Wang, S-C., Lien, H-C., Xia, W., Chen, I-F., Lo, H-W., Wang, Z., Ali-Seyed, M., Bartholomeusz, G., OuYang, F., Giri, D.K. and Hung, M.-C. Binding at and transactivation of COX-2 promoter by nuclear tyrosine
kinase receptor ErbB2. Cancer Cell 6:251-261, 2004.
9. Zhou, B.P., Deng, J., Xia ,W., Xu, J., Li, Y.M., Gundaz, M. and Hung, M.-C. Dual regulation of Snail by
GSK-3-mediated phosphorylation in control of epithelial-mesenchymal transition. Nature Cell Biology
6:931-940, 2004.
10. Li, Y.M., Pan, Y., Wei, Y., Cheng, X., Zhou, B., Tan, M., Zhou, X., Xia, W., Hortobagyi, G.N., Yu, D. and
Hung, M.-C. Upregulation of CXCR4 is essential for HER2-mediated tumor metastasis. Cancer Cell
6:459-469, 2004.
11. Lo, H-W., Hsu, S-C., Ali-Seyed, M., Gunduz, M., Xia, W., Wei, Y., Bartholomeusz, G., Shih, J-Y.,and Hung,
M-C. Nuclear interaction of EGFR and STAT3 in the activation of iNOS/NO pathway. Cancer Cell 7:575589, 2005.
12. Ding, Q., Xia W., Liu, J-C., Yang, J-Y., Lee, D-F., Xia, J., Bartholomeusz, Li, Y., Pan, Y., Li, Z., Bargou,
RC., Qin, J., Lai, C-C., Tsai, F-J. Tsai, C-H. and Hung, M-C. Erk1/2 associates with and primes GSK-3
for its inactivation resulting in upregulation of -catenin. Molecular Cell 19:159-170, 2005.
13. Cha, T-L., Zhou, BP., Xia, W., Wu, Y., Yang, C-C., Chen, C-T., Ping, B. Otte, A.P. and Hung, M-C. Aktmediated phosphorylation of EZH2 augments methylation of lysine 27 in histone H3. Science 310:306-310,
2005.
14. Wang, S-C., Nakajima, Y., Yu, Y-L., Li, L-Y., Chen, C-T, Hawke, D., Kobayashi, R. and Hung, M-C.
Tyrosine phosphorylation controls protein stability of PCNA. Nature Cell Biology. 8:1359-1368, 2006.
15. Huang, W-C., Ju, T-K., *Hung, M-C. and *Chen, C-C. Phosphorylation of CBP by IKKα promotes cell
growth by switching the binding preference of CBP from p53 to NF-κB. Molecular Cell 26:75-87, 2007.
*co-coresponding author.
16. Xie, X., Xia, W., Li, Z., Kuo, H-P.,Liu, Y., Li, Z., Ding, Q., Zhang, S., Spohn, W., Yang, Y., Wei, Y., Lang, JY., Evans, D.B., Chiao, P.J., Abbruzzese J.L. and Hung, M-C. Targeted expression of BikDD eradicates
pancreatic tumors in noninvasive imaging models. Cancer Cell, 12:52-65, 2007.
17. Lee, D-F., Kuo, H-P., Chen, C-T., Hsu, J-M., Sun, H-L., Chou, C-K., Wei, Y., Li, L-Y.,Ping, B., Huang, WC., He, X., Hung, J-Y., Lai, C-C., Ding, Q., Su, J-L., Yang, J-Y., Sahin, A.A., Hortobagyi, G.N., Tsai, F-J.,
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Principal Investigator/Program Director (Last, First, Middle):
Hung, Mien-Chie
Tsai, C-H. and Hung, M-C. Suppression of TSC1 by IKKb confers tumor angiogenesis through the mTOR
pathway. Cell 130:440-455, 2007.
18. Yang, J-Y., Zong, C.S., Xia, W., Yamaguchi, H., Ding, Q., Xie, X., Lang, J-Y., Lai, C-C., Chang, C-J.,
Huang, W-C., Huang, H., Kuo, H-P., Lee, D-F., Li, L-Y., Lien H-C., Cheng, X, Chang, K-J., Hsiao, C-D.,
Tsai, F-J., Tsai, C-H., Sahin, AA., Muller, WJ., Mills, GB., Yu, D., Hortobagyi, GN. and Hung, M-C. Erk
promotes tumorigenesis by inhibiting Foxo3a via MDM2-mediated degradation. Nature Cell Biology
10:138-148, 2008.
19. Zhang, W., Tsan, R., Wu, Q., Huang, W-C., Chiu, C-H., *Fidler, I.J. and *Hung, M-C. Survival of cancer
cells is maintained by kinase-independent EGFR. Cancer Cell 13:383-393, 2008. *Co-Corresponding
authors
20. Lee, D-F., Kuo, H-P., Liu, M., Chou, C-K., Xia, W., Du, Y., Shen, J., Shen, J., Chen, C-T., Huo, L., Hsu, MC., Li, C-W., Ding, Q., Liao, T-L., Lai, C-C., Lin, A-C. Chang, Y-H, Tsai, S-F., Li, L-Y. and Hung, M-C.
KEAP1 E3 ligase-mediated down regulation of NF-B signaling by targeting IKK. Molecular Cell 36: 131140, 2009.
21. Kuo, H-P., Lee, D-F., Chen, C-T., Liu, M., Chou, C-K., Lee, H-J., Xie, X., Wei, Y., Xia, W., Zhang, W., Yi,
D., Yang, J-Y., Huang, T-H., Yen,C-J., Tan, M., Xing, G., Zhao, Y., Lin, C-H., Tsai, S-F., Fidler, IJ and
Hung, M-C. ARD1 stablization of TSC2 suppresses tumorigenesis via the mTOR signaling pathway.
Science Signaling 3 (108): ra9, 2010
22. Huo LF, Wang YN, Xia W, Hsu SC, Lai CC, Li LY, Chang WC, Wang Y, Hsu MC, Yu YL, Huang TH, Ding
QQ, Chen CH, Tsai CH, Hung M-C. RNA helicase A is a DNA-binding partner for EGFR-mediated
transcriptional activation in the nucleus. PNAS 107(37):16125-16130 (Epub online August 27), 2010.
23. Wei Y, Chen YH, Li LY, Lang J, Yeh SP, Shi B, Yang CC, Yang JY, Lin CY, Lai CC, Hung MC. CDK1dependent phosphorylation of EZH2 suppresses methylation of H3K27 and promotes osteogenic
differentiation of human mesenchymal stem cell. Nature Cell Biology (Epub online Dec 5), 2010.
24. Chang CJ, Yang JY, Xia W, Chen CT, Xie X, Chao CH, Woodward WA, Hortobagyi GN, Hung MC. EZH2
promotes expansion of breast cancer tumor initiating cells through activation of RAF--catenin signaling.
Cancer Cell (in press), 2010.
25. Hsu JM, Chen CT, Chou CK, Kuo HP, Li LY, Lin CY, Lee HJ, Wang YN, Liu M, Liao HW, Shi B, Lai CC,
Bedford MT, Tsai CH, Hung MC. Crosstalk between R1175 methylation and Y1173 phosphorylation
negatively modulates EGFR-mediated ERK activation. Nature Cell Biology (in press), 2010.
26. Chang CJ, Chao CH, Xia W, Yang JY, Xiong Y, Li CW, Yu WH, Rehman SK, Hsu J, Lee HH, Liu M, Chen
CT, Yu D, Hung MC. p53 regulates epithelial-mesenchymal transition (EMT) and stem cell properties
through modulation of miRNAs. Nature Cell Biology (in press), 2010.
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