醫學研究科

[醫研科行政業務] [動物研究實驗室]

[心臟血管研究室] [神經結構與功能研究室] [流行病學研究室]

[細胞藥理學研究室] [基因工程研究室] [感染疾病與免疫學研究室] [癌症基因體研究室] 

Welcome!
Laboratory of Genetic Engineering is located at 4th Floor of the Building of Medical Research in the Veterans General Hospital- Kaohsiung.

Principal Investigator: Ph. D. Ming-Hong Tai（本院特聘研究員）

     TEL: (07) 342-2121 ext. 1511     FAX: (07)346-8056

    Address: 高雄市左營區大中一路386號 高雄榮總 教學研究部                 

                   Department of Medical Education and Research

                   Veterans General Hospital-Kaohsiung

                    386 Ta-Chung 1st Road Kaohsiung,

                   Taiwan 813

    E-mail: prlin@vghks.gov.tw

主持人(Principal investigator)　其他成員 (Members)

Associated Investigator

    Ph.D. Tai, Ming-Hong

     戴明泓 博士(本院特聘研究員) TEL: (07)342-2121 ext. 1510 E-mail：mhtai@isca.vghks.gov.tw

• 研究主題

• Research interests

• Education

• Publications              

1.?鑑別新的分子標幟以應用於肝炎的診斷及治療

肝癌在台灣高居死亡率之冠, 然而肝癌的致病機轉目前仍不清楚。過去三年來, 我們分析腫瘤抑制基因PTEN在肝癌組織的表現發現: 將近40%的肝癌病人其肝癌組織有PTEN基因表現缺失的情況。基於此, 我們運用腺病毒載體回復肝癌細胞PTEN基因的表現後,發現此方式可有效的降低肝癌細胞在裸鼠身上生長的情形。 目前, 我們嘗試發展原發性肝癌的動物模式,以用於評估以PTEN 基因對肝癌動物模式進行治療之效能及可行性。

2. 血管新生的分子機制

血管新生--即生成新血管的過程--在正常的生理狀態 下及許多人類疾病 (如:癌症、類風濕性關節炎)上扮演 極重要的角色。此現象的發生,端賴眾多促進或抑制血管新生的因子的參與。我們研究室已成功的生產並純畫出血管新生抑制因子(endostatin及vasostatin),及血管心生促進因子(bFGF,aFGF,VEGF及HDGF)。藉著活體外(in vitro)及活體內(in vivo)的相關研究，我們希望可以開發這些因子在臨床上的應用方向，同時對血管新生的機制有更清楚的了解。

3. 以神經生長因子促進神經再生

因為神經細胞無法再生的特性，使得 神經創傷後或神經退化後再促進神經再生的工作顯得更加艱巨。於目前的研究中，我們已證實以神經生長因子基因治療脊髓傷害後的大鼠，其神經受損情形有減緩的現象，但同時也加劇其神經痛的情況。未來，我們將繼續探索合併基因治療的方法,以提升神經再生因子基因治療之發展潛能。

Research interests

Genetic engineering has become the premium technology to enhance the national economies and to improve the welfare of human beings. The ultimate goal of our laboratory is to develop gene-based strategies for diagnosis and treatment of intractable diseases. At present, our groups are focusing on the following biological questions:

1. Identification of Novel Molecular Markers for Diagnosis and Treatment of Hepatocellular Carcinoma (HCC).

HCC is the leading cause for mortality in Taiwan. However, the mechanism underlying liver carcinogenesis remains unclear. In the last three years, we analyzed the expression of tumor suppressor gene PTEN in HCC specimens and found that loss of PTEN expression occurs in nearly 40% of HCC patients. Subsequently, we utilized adenovirus vector to restore PTEN expression and found that PTEN gene delivery effectively reduced the growth of hepatoma in nude mice. At present, we are developing orthotopic hepatoma model to evaluate the efficacy of PTEN gene delivery for treatment of hepatoma in immune competent animals.

2. Molecular Mechanism of Angiogenesis

Angiogenesis, the process of growing new blood vessels, plays an important role in physiological process and pathogenesis of human diseases such as cancer, rheumatoid arthritis. Many positive and negative factors participate in the process of angiogenesis. In our laboratory, we have generated recombinant angiogenesis inhibitors such as endostatin, vasostatin, and angiogenic factors such as bFGF, aFGF, VEGF, and HDGF. By studying the functions of these factors in vitro and in vivo, we hope to explore the clinical application of these factors, but also shed lights on the mechanism of angiogenesis.

3. Neuroregeneration by gene delivery of neurotrophic factors

To promote regeneration of central nerve system (CNS) after trauma or degeneration is considered a huge task because of the inability of CNS to regrow. In our recent studies, we demonstrated the feasibility of using gene delivery of trophic factor, GDNF to promote the recovery of rats after spinal cord injury, to alleviate the neuropathic pain in rats with nerve injury. In the future, we will also explore the potential and efficacy of combinatory gene therapy to enhance neuroregeneration.
　

Education
1980-1984 B. S., Chemistry　　National Cheng-Kung University
1984-1986 M. S., Biochemistry　　National Taiwan University
1988-1993 Ph. D., Biochemistry　　Baylor College of Medicine
1993-1994 Postdoctoral fellow　　Baylor College of Medicine
1994-1996 Postdoctoral fellow　　The Scripps Research Institute

A. 期刊論文

1.  Sheu, S.-J., Chou, L.-C., Bi, Y.-S., Chen, J.-F., Lin, H.-C., Lin, P.-R., Lam, H.-C. and Tai, M.-H.* Suppression of Choroidal Neovascularization by Intramuscular Polymer-based Gene Delivery of Vasostatin Exp. Eye Res. In press (SCI; *: corresponding author) (IF: 2.611; 7/41=17.07%)

2.  Wu, P.-C., Yang, L.-C., Kuo, H.-K., Huang, C.-C., Tsai, C.-L., Lin, P.-R., Wu, P.-C., Shin, S.-J., Tai, M.-H.* Inhibition of corneal angiogenesis by local application of vasostatin Molecular Vision 11:28-35, 2005 (SCI; *: corresponding author) (IF: 2.777; 6/41=14.63%)

3.  Tai, M.-H, Wang L.-L., Kay L.H. Wu, Julie Y.H. Chan Increased superoxide anion in rostral ventrolateral medulla contributes to hypertension in spontaneously hypertensive rats via interactions with nitric oxide Free Radical Biology & Medicine 38(4):450-62, 2005 (SCI) (IF: 5.063; 43/261 = 16.47%)

4.  Chou, A. K., Yang, L. C., Lin, T. R., Lin, P. R., Tai, M. H.* Amelioration of paraplegia with spinal ischemia by gene delivery of glial cell line-derived neurotrophic factor Brain. Res. Mol. Brain. Res. 133 (2):198-207, 2005 (SCI; *: corresponding author) (IF: 2.107; 100/198 = 50.50%)

5.  Huang CC, Chuang, J.-H., Chou, M.-H., Wu, C.-L., Chen, C.-M., Wang, C.-C., Chen, Y.-S., Chen, C.-L. and Tai, M-H. Matrilysin (MMP-7) is a major matrix metalloproteinase up-regulated in biliary atresia-associated liver fibrosis. Modern Pathology in press 2005 (SCI)

6.  Hu, T.-H., Huang, C.-C., Wu, C.-L., Lin, P.-R., Liu, S.-Y., Lin, J.-W., Chuang, J.-H., Tai, M.-H* Increased Endostatin/Collagen XVIII Expression Correlates with Elevated VEGF Level and Poor Prognosis in Hepatocellular Carcinoma. Modern Pathology 18(5): 663-72, 2005 (SCI; *: corresponding author) (IF: 3.643; 10/64 = 15.62%)

7.  Hsiao CC, Huang CC, Sheen JM, Tai, M-H, Chen CM, Huang LL, Chuang JH. Differential expression of delta Differential expression of delta-like gene and protein in neuroblastoma, ganglioneuroblastoma and ganglioneuroma. Modern Pathology 18: 656-662, 2005 (SCI)

8.  Chuang, J.-H., Wang, Pei-Wen and Tai, M-H. An adipocentric view of liver fibrosis and cirrhosis The Chung Gung Medical Journal 27 (12): 855-868, 2004.

9.  Cho, F. N., Kan, Y. Y., Yang, T. L., Huang, H. P., Hsu, P. H., Tai, M. H. Prenatal diagnosis of sharp-angled lumbosacral kyphosis with myelomeningocele and spina bifida in a fetus. Journal of Ultrasound Medicine 23(8):1115-9, 2004. (SCI)

10. Tai, M. H., Hsiao M, Chan JY, Lo WC, Wang FS, Liu GS, Howng SL, Tseng CJ. Gene delivery of endothelial nitric oxide synthase into nucleus tractus solitarii induces biphasic response in cardiovascular functions of hypertensive rats American Journal of Hypertension 17(1): 63-70, 2004 (SCI) (IF: 3.382; 13/51 = 25.49%)

11. Hu, T. H., Huang, C. C., Ma, Y. L., Liu L. F., Liang, H. T., Kao, Y. H., Lin, P. R., Goto, S., Chen, C. L., Lee, C. H., and Tai, M. H.* The Expression of Hepatoma-derived Growth Factor in Hepatocellular Carcinoma: A novel prognostic factor Cancer 98(7):1444-56, 2003 (SCI; *: corresponding author) (IF: 4.434; 22/120 = 17.89%)

12. Tai, M. H., Cheng, H., Wu, J.P., Liu, Y.L., Lin, P.R., Kuo, J.S., C.J.Tseng, and S.F. Tzeng Gene transfer of glial cell line-derived neurotrophic factor promotes functional recovery following spinal cord contusion Experimental Neurology 183(2):508-15, 2003 (SCI) (IF: 3.676; 42/198 = 21.21%)

13. Hu, T. H., Huang, C. C., Lin, P. R., Chang, H. W., Ger, L. P., Lin, Y. W., Changchien, C. S., Lee, C. M., and Tai, M. H.*. Expression and prognostic role of tumor suppressor gene PTEN/MMAC1/TEP1 in hepatocellular carcinoma. Cancer 97, 1929-40, 2003. (SCI; *: corresponding author) (IF: 4.434; 22/123 = 17.89%)

14. Chau, Y. P., Liu, T. J., Lin, S. Y., Chen, J. H. C., Tai, M. H.*. Endostatin induced autophagic cell death in human endothelial cells Histology and Histopathology 18 (3): 715-26, 2003 (SCI; *: corresponding author) (IF: 1.83; 25/64 = 39.06%)

15. Lee, Y. C., Chien, C. L., Sun, C. N., Huang, C. L., Huang, N. K., Chiang, M. C., Lai, H. L., Lin, Y. S., Chou, S. Y., Wang, C. K., Tai, M. H., Liao, W. L., Lin, T. N., Liu, F. C., Chern, Y. Characterization of the rat A2A adenosine receptor gene: a 4.8-kb promoter-proximal DNA fragment confers selective expression in the central nervous system Eur. J. Neurosci. 18(7):1786-96, 2003. (SCI) (IF: 3.876; 37/198 = 18.68%)

16. Lin, C. R., Yang, L. C., You, H. L., Lee, C. T., Tai, M. H., Tan, P. H., Lin, M. W., and Cheng, J. T. Antinociceptive Potentiation and Attenuation of Tolerance by Intrathecal Electric Stimulation in Rats. Anesth. Analg. 96, 1711-1716 2003. (SCI)

17. Wang, Y. F., Lee, S. B., Cheng LC, Tai, M. H., Su, I. J. Detection of serum antibodies to three different recombinant antigens of human herpesvirus 8 by immunoblotting: seroprevalence studies in Taiwan. Clin. Chim. Acta. 320(1-2):37-42, 2002 (SCI)

18. Lin, C. R., Tai, M. H., Cheng, J. T., Chou, A. K., Wang, J. J., Tan, P. H., Marsala, M., Yang, L. C. Electroporation for direct spinal gene transfer in rats  Neuroscience Letters 317:1-4, 2002 (SCI) (IF: 1.967; 107/198 = 54.04%)

19. Krushel L. A., Tai, M. H., Cunningham, B. A., Edelman, G. M. Crossin, K. L. N-CAM domains and intracellular signaling pathways involved in the inhibition of astrocyte proliferation. Proc. Natl. Acad. Sci. USA. 95(5):2592-2596, 1998.  (SCI)

20. Crossin, K. L., Tai, M. H., Krushel L. A., Mauro, V. P., Edelman, G. M.  Glucocorticoids receptor pathways are involved in the inhibition of astrocyte proliferation. Proc. Natl. Acad. Sci. USA. 94:2687-2692, 1997. (SCI)

21. Jayakumar, A.*, Tai, M. H.*, Huang, W. Y., Al-Feel, W., Hsu, M., Abu-Elheiga, L., Chirala, S. S., Wakil, S. J. Human fatty acid synthase: properties and molecular cloning. Proc. Natl. Acad. Sci. USA. 92(19): 8695-9, 1995. (*: equal contribution)  (SCI)

22. Tai, M. H., Chirala, S. S., Wakil, S. J. Roles of Ser101, Asp236, and His237 in catalysis of thioesterase II and of the C-terminal region of the enzyme in its interaction with fatty acid synthase. Proc. Natl. Acad. Sci. USA. 90 (5):1852-6, 1993. (SCI)

B. 研討會論文

1.      Tai, M. H., Crossin, K. L., Edelman, G. M.  Cytotactin upregulates gene expression of translationally controlled tumor protein in chicken embryo brain cells.  Society for Neuroscience Vol. 23:92, 45.7, 1997.

2.      Crossin, K. L., Tai, M. H., Krushel, L. A., Mauro, V. P., Edelman, G. M.  Glucocorticoid receptor pathways are involved in inhibition of astrocyte proliferation.  Society for Neuroscience Vol. 23:70, 37.1, 1997.

3.      Krushel, L. A., Tai, M. H., Ranheim. T. S., Cunningham, B. A., Edelman, G. M., Crossin, K. L.  Signal pathways associated with inhibition of glial proliferation by N-CAM.  Society for Neuroscience Vol. 23:70, 37.2, 1997.

4.      Lin, P. R., Tai, M. H. Cloning, expression and purification of the cytoplasmic domain of neuronal adhesion molecule DCC. Abstracts in Annual Meeting of Society for Basic Neuroscience, 1997 中華民國基礎神經科學學會

5.      Tai, M. H., Chiang, C. Y., Lin, P. R., Tseng, C. J.  Mapping the transactivation domains within the cytoplasmic domain of Deleted in Colorectal Cancer (DCC). 28^th Annual Meeting of Society for Neuroscience Vol. 24:1069, 424.17, 1998.

6.      J. H. C., Wu, S. N., Tai, M. H. Electrophysiological studies on the effects of endostatin in endothelial cells Special conference “New Targets for Cancer Intervention” by American Association for Cancer Research, 2000.

7.      Ming-Hong Tai, Pey-Ru Lin, Tsong-Hwei Hu PTEN Gene delivery for suppression of hepatoma. Molecular Therapy Vol. 3 No. 5: S341-963, May 2001. 4^th Annual Meeting for American Society of Gene Therapy, Seattle, USA

8.      James Heng-Chi Chen, Sheng-Nan Wu, and Ming-Hong Tai Endostatin Induced Calcium Rise and Stimulated Large-conductance, Calcium-activated Potassium Channel in Endothelial Cells Vol. 1 No. 913 16^th Protein Society Meeting, 2002, San Diego, USA

9.      Pey-Ru Lin, Ming-Hong Tai PTEN gene delivery suppressed PTEN-defective hepatoma Abstract Book No. 238, 11^th Annual Congress of European Society of Gene Therapy, 2003. Edinburg, UK.

10.  Ming-Hong Tai, An-Kuo Chou, Yu-Ming Kuo Gene Delivery of Glial Cell line-Derived Neurotrophic Factor Ameliorated Paraplegia in Rats after Spinal Ischemia. 34th Annual Meeting of The Society for Neuroscience, 2004 San Diego, USA

11.  Guei-Sheung Liu, Chiou-Lian Lai, Sheng-Long Howng and Ming-Hong Tai Peripheral Gene Delivery of Glial Cell Line-derived Neurotrophic Factor Alleviated Neurological Deficits in Diabetic Rats Molecular Therapy Vol. 11 (1): S549, June 2005. 8^th Annual Meeting for American Society of Gene Therapy, St. Louis, USA 

C. 專書及專書論文

1.        Tai, M. H. “Expression, Purification, and Mutagenesis Studies of Rat Mammary Gland Medium-chain S-acyl Fatty Acid Synthase Thioesterase II (TE II) Ph.D. Thesis, 1993. Dept. of Biochemistry, Baylor College of Medicine, USA.

2.        Tai, M. H. Chapter 14 Expression of tumor suppressor gene PTEN in hepatocellular carcinoma Handbook for Immunohistochemistry and In Situ Hybridization Vol. 2 (published by Elsevier Science/Academic Press; 2005 in press)

D. 技術報告及其他

1.   Tai, M. H.「評估腫瘤生長與轉移之冷光癌症模式」(國科會計劃編號NSC 93-2622-B-075B-001-CC3; 技術移轉至冷泉港生物科技公司)

2.   Tai, M. H. Liu, S. Y. “ST104P, An Anti-angiogenic Agent” (Application for US patent)

Members