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Dr. Tien Hsu was recruited to the National Central University in August 2013. Previously he was Professor of Medicine at the Boston University School of Medicine. The major research interest in Dr. Hsu’s laboratory is to understand the origin of cancer and the mechanism of its growth. In the 1990s, Dr. Hsu pioneered the study using multiple model organisms, including fruit fly, mouse, and human cells, for functional comparison of tumor-related genes in embryonic development. He has contributed greatly in the understanding of tumor suppressor genes VHL and anti-metastasis gene Nm23. He serves on the advisory board of the International VHL Disease Alliance. He was elected in 2012 as the President of International Congress of NDPK/Nm23/awd Gene Family. He also served as grant review panel members of NIH (USA), and government agencies of other countries such as Italy, Israel, United Kingdom, Canada, Holland, etc. Traditionally, cancer research has been focused on killing cancer cells. Such strategy has shown only limited success in the almost 50 years of “War on Cancer.” Dr. Hsu believes that we need to rethink our strategy, and should focus on the role of stromal cells, which promote inflammatory reaction and support stem cell survival. It is now discovered that tumor growth and stem cell maintenance are dependent on the surrounding tissues and cells (the stroma). Controlling organ pathology by modulating the stromal function should present a gentler and more effective containment of many diseases including cancer. The concept is to contain the cancer tissue and prevent malignancy, but not necessarily to kill cancer cells. Such new direction requires a systems biology view of the interaction between the diseased tissue and the entire body. Dr. Hsu’s current research is focused on stromal biology, characterizing the function and therapeutic potential of the tumor microenvironment. He recently established that metabolic abnormality in VHL mutant cells can lead to ER stress and tissue inflammation, eventually resulting in clear-cell renal cell carcinoma formation. More recently he initiated an 10-million NTD/year integrated program project to analyze immune cell populations that mark the transition from inflammation to renal cell carcinoma at the single-cell level. His team has also won the second prize (total 255 international teams) in Qualcomm Tricorder XPrize Competition 2012-2017 (https://tricorder.xprize.org/). He has recently founded the Center for Chronic Disease Research and is leading the effort in Taiwan to build a community health network focusing on chronic disease research and management. Publications: 1. Hsu, T., Wei, R., Dawson, M., and Karam, J.D. (1987) Identification of two bacteriophage T4 genes that may have roles in transcription and DNA replication. J. Virol. 61: 366-374. 2. Winter, R.B., Morrissey, L., Gold, L., Hsu, T., and Karam, J. (1987) The bacteriophage T4 regA protein binds to mRNAs and prevents translation initiation. Proc. Natl. Acad. Sci. (USA) 84: 7822-7826. 3. Liang, Y., Wei, R., Hsu, T., Alford, C., Dawson, M., and Karam, J. (1988) Autogenous regulation of the regA gene of bacteriophage T4: derepression of translation. Genetics 119: 739-749. 4. Andrake, M., Guild, N., Hsu, T., Gold, L., Tuerk, C., and Karam, J. (1988) The DNA polymerase of bacteriophage T4 is an autogenous translational repressor. Proc. Natl. Acad. Sci. (USA) 85: 7942-7946. 5. Hsu, T. and Karam, J. (1990) Transcriptional mapping of a phage T4 DNA replication gene cluster: sites for transcription initiation, transcription termination and mRNA processing. J. Biol. Chem. 265: 5303-5316. 6. Hsu, T., Gogos, J.A., Kirch, S.A., and Kafatos, F.C. (1992) Multiple zinc finger forms resulting from developmentally regulated alternative splicing of a transcription factor gene. Science 257: 1946-1950. [Highlighted in "This week in Science"] 7. Gogos, J.A., Hsu, T., Bolton, J., and Kafatos, F.C. (1992) Sequence discrimination by alternatively spliced isoforms of a DNA binding zinc finger domain. Science 257: 1951-1955. [Highlighted in "This week in Science"] 8. Hsu, T., King, D.L., LaBonne, C., and Kafatos, F.C. (1993) A Drosophila single-stranded DNA/RNA-binding factor contains a high-mobility-group box and is enriched in the nucleolus. Proc. Natl. Acad. Sci. (USA) 90: 6488-6492. 9. Hsu, T., Gogos, J.A., Bolton, J., and Kafatos, F.C. (1993) Alternatively spliced isoforms of a Cis2-His2 zinc-finger domain: developmental regulation and binding-site selection. Annals of The New York Academy of Sciences 684: 218-219. 10. Karam, J.D., Hsu, T., and Miller E.S. (1994) Large scale isolation of mRNA from T4-infected cells, in The Molecular Biology of Bacteriophage T4, Karam et al, eds., pp. 468-469. (American Society of Microbiology Press, Washington, D.C.) 11. Hsu, T. (corresponding author), Bagni, C., Sutherland, J.S., and Kafatos, F.C. (1996) The transcription factor CF2 is a mediator of EGF-R-activated dorsoventral patterning in Drosophila oogenesis. Genes & Development 10: 1411-1421. [Selected for Cover Photo]. 12. Dobens, L.L., Hsu, T., Twombly, V., Gelbart, W.M., Raftery, L.A., and Kafatos, F.C. (1997) The Drosophila bunched gene is a homologue of the growth factor stimulated mammalian TSC-22 sequence and is required during oogenesis. Mech. Dev. 65:197-208. 13. Yeh, L.-S, Hsu, T., and Karam, J.D. (1998) Divergence of a DNA replication gene cluster in the T4-related bacteriophage RB69. J. Bacteriology 180: 2005-2013. 14. Mantrova, E.Y.† and Hsu, T. (1998) Down-regulation of transcription factor CF2 by Drosophila Ras/MAP kinase signaling in oogenesis: cytoplasmic retention and degradation. Genes & Development 12: 1166-1175. 15. Papenbrock, T., Peterson, R.L., Lee, R.S., Hsu, T., Kuroiwa, A., and Awgulewitsch, A. (1998) The murine Hoxc-9 gene contains a structurally and functionally conserved enhancer. Developmental Dynamics 212: 540-547. 16. Hsu, T. and Mantrova, E.Y.† (1999) Developmental specificity of the EGF receptor signaling: Feedback loops and novel regulatory mechanisms. Miami Nature Biotechnology Short Reports 10: 97. 17. Mantrova, E.Y.†, Schulz, R.A., and Hsu, T. (1999) Oogenic function of the myogenic factor D MEF2: negative regulation of the Dpp type I receptor thick veins. Proc. Natl. Acad. Sci. (USA) 96: 11889-11894. 18. Adryan, B.#, Decker, H.-J., Papas, T.S., and Hsu, T. (2000) Tracheal development and the von Hippel-Lindau tumor suppressor homolog in Drosophila. Oncogene 19: 2803-2811. 19. Hsu, T. (corresponding author) and Schulz, R.A. (2000) Sequence and functional properties of Ets genes in the model organism Drosophila. Oncogene 19: 6409-6416. [Review] 20. Hsu, T. (corresponding author), McRackan, D¶, Vincent, T.S. and de Couet, H.G. (2001) The Drosophila Pin1 prolyl isomerase Dodo is a MAP kinase signal responder during oogenesis. Nature Cell Biology 3: 538-543. [Accompanied by News and Views. Nature Cell Biology 3: E136-E137.] 21. Bagni, C., Bray, S., Gogos, J.A., Kafatos, F.C. and Hsu, T. (2002) The Drosophila zinc finger transcription factor CF2 is a myogenic marker downstream of MEF2 during muscle development. Mechanisms of Development 117: 265-268. 22. Dammai, V.† and Hsu, T. (2003) EGF-dependent and independent activation of MAP kinase during Drosophila oogenesis. Anatomical Record 272A: 377-382. 23. Lavenburg, K.R.†, Ivey, J.¶, Hsu. T. (co-corresponding author) and Muise-Helmericks, R. (2003) Coordinated functions of Akt and Ets1 in tubulogenesis. FASEB J. 17: 2278-2280 [Selected for cover photo]. 24. Dammai, V.†, Adryan, B.#, Lavenburg, K.R.† and Hsu, T. (2003) Drosophila awd, the homolog of human nm23, regulates FGF receptor levels and functions synergistically with shi/dynamin during tracheal development. Genes & Dev. 17: 2812-2824. 25. Hsu, T., Trojanowska, M. and Watson, D.K. (2004) Ets proteins in biological control and cancer. J. Cell. Biochem. 91: 896-903. [Review] 26. Hsouna, A.†, Watson, D.K. and Hsu, T. (2004) Developmental expression patterns of D-ets4, the Drosophila homologue of human Pdef. Mech. Dev.-Gene Expr. Patterns 5: 285-289. 27. Cavaliere, V., Donati, A., Hsouna, A.†, Hsu, T. and Gargiulo, G. (2005) The dAkt kinase controls follicle cell size during Drosophila oogenesis. Developmental Dynamics 232: 845-854. 28. Adereth, Y.#, Champion, K. J.#, Hsu, T. and Vincent Dammai (2005) Site-directed mutagenesis using Pfu-DNA polymerase and T4-DNA ligase. BioTechniques 38: 864, 866, 868. 29. Pei, H., Li, C., Adereth, Y.#, Hsu, T., Watson, D.K. and Li, R. (2005) Caspase-1 is a direct target gene of ETS1 and plays a role in ETS1-induced apoptosis. Cancer Research 65: 7205-7213. 30. Adereth, Y.#, Dammai, V., Kose, N., Li, R. and Hsu, T. (2005) RNA-dependent integrin 3 protein localisation regulated by the Muscleblind-like protein MLP1. Nature Cell Biology 7: 1240-1247 [Accompanied by News and Views Nature Cell Biology 7: 1155-1156] [Highlighted in Nature Cell Migration Gateway, Dec. 2005] 31. Arquier, N., Vigne, P., Duplan, E., Hsu, T., Therond, P.P., Frelin, C. and D'Angelo, G. (2006) Analysis of the hypoxia-sensing pathway in Drosophila melanogaster. Biochem. J., 393: 471-480. 32. Hsu, T. (co-corresponding author), Adereth, Y.†, Kose, N. and Dammai, V. (2006) Endocytic function of Von Hippel-Lindau tumor suppressor protein regulates surface localization of FGF receptor 1 and cell motility. J. Biol. Chem. 281: 12069-12080. [Editor's Choice, Cancer, Science's STKE, May 2006] 33. Hsouna, A.†, Lawal, H.O., Izevbaye, I. and Hsu, T. (co-corresponding author) and O'Donnell, J.M. (2007) Drosophila dopamine synthesis pathway genes regulate tracheal morphogenesis. Dev. Biol. 308: 30-43. 34. Nallamothu, G.†, Woolworth, J.A.#, Dammai, V. and Hsu, T. (2008) awd, the homolog of metastasis suppressor gene Nm23, regulates Drosophila epithelial cell invasion. Mol. Cell. Biol. 28: 1964–1973. 35. Chintalapudi, M. R.†, Markiewicz, M., Kose, N, Dammai, V., Championl, K.J.#, Hoda, R. S., Trojanowska, M. and Hsu, T. (2008) Cyr61/CCN1 and CTGF/CCN2 mediate the pro-angiogenic activity of VHL mutant renal carcinoma cells. Carcinogenesis 29: 696-703. 36. Champion, K.J.#, Guinea, M.†, Dammai, V. and Hsu, T. (2008) Endothelial function of von Hippel-Lindau tumor suppressor gene: control of FGF receptor signaling. Cancer Research 68: 4649-4657. [IF: 12.7; 16/211, Cancer Research] 37. Bu, S., Kapanadze, B., Hsu, T. and Trojanowska, M. (2008) Opposite effects of dihydrosphingosine 1-phosphate and sphingosine 1-phosphate on TGFbeta/Smad pathway are mediated through the PTEN/PPM1A dependent pathway. J. Biol. Chem. 283:19593-19602. 38. Mahajan, S., Dammai, V., Hsu. T. and Kraft, A.S. (2008) Hypoxia-inducible factor-2 regulates the expression of TRAIL receptor DR5 in renal cancer cells. Carcinogenesis 29: 1734-1741. 39. Nallamothu, G.†, Dammai, V. and Hsu, T. (2009) Developmental Function of Nm23/awd - A Mediator of Endocytosis. Mol. Cell. Biochm. 329: 35-44. [Review] 40. Woolworth, J.A.#, Nallamothu, G.†, and Hsu, T. (2009) The Drosophila metastasis suppressor Nm23 homolog, awd, regulates epithelial integrity during oogenesis. Mol. Cell. Biol. 29: 4679-4690. [Selected for cover photo] 41. Duchi, S.#, Fagnocchi, L., Cavaliere, V., Hsouna, A.†, Gargiulo, G. and Hsu, T. (2010) Drosophila VHL tumor suppressor gene regulates epithelial morphogenesis by promoting microtubule stability. Development 137:1493-1503. [Featured "In This Issue"] 42. Hsouna, A.†, Kose, N., Guinea, M.†, Dammai, V. and Hsu, T. (2010) Drosophila von Hippel-Lindau tumor suppressor gene regulates epithelial tubule migration and lumen formation by promoting endocytosis. Mol. Cell. Biol. 30:3779-3794. [Featured in "Spotlight"][Selected for cover photo] 43. Hsu, T. (2011) NME Genes in Epithelial Morphogenesis. Naunyn-Schmiedeberg Arch. Pharm. 384: 363-372. [Review] 44. Liby, T.A., Spyropoulos, P., Lindner, H.B., Eldridge, J., Beeson, C., Hsu, T. and Muise-Helmericks, R.C. (2012) Akt3 Controls VEGF secretion and angiogenesis in ovarian cancer cells. Int. J. Cancer. 130: 532-543. 45. Hsu, T. (2012) Complex cellular functions of the von Hippel-Lindau tumor suppressor gene: Insights from model organisms. Oncogene 31: 2247-2257. [Invited Review] 46. Bader, H. L.† and Hsu, T. (2012) Systemic VHL gene functions and the VHL disease. FEBS Lett. 586:1562-1569. [Invited Review] 47. Bader, H. L.†, Pritchett, T.L.†, and Hsu, T. (2012) Hematopoietic Functions of the Tumor Suppressor Von Hippel Lindau (VHL) in the Etiology of Hemangioblastoma. Blood 120: 2425-2425. 48. Ignesti, M., Barraco, M., Nallamothu, G.†, Woolworth, J.A.#, Duchi, S., Gargiulo, G., Cavaliere, V. and Hsu, T. (2014) Notch signaling during development requires the function of awd, the Drosophila homolog of human metastasis suppressor gene Nm23. BMC Biology. 12:12. [IF: 6.97; 31/204, Biochemistry, Genetics, and Molecular Biology] 49. Lin, C.H.#, Dammai, V. Adryan, B. and Hsu, T. (2015) Interaction between Nm23 and the tumor supressor VHL. Naunyn-Schmiedeberg Arch. Pharm. 388: 143-152. [IF: 2.38; 204/773, Pharmacology] 50. Pritchett, T.L.†, Bader, H.L.†, Henderson, J. and Hsu, T. (2015) Conditional inactivation of the mouse von Hippel–Lindau tumor suppressor gene results in wide-spread hyperplastic, inflammatory, and fibrotic lesions in the kidney. Oncogene, 34: 2631-2639. [IF: 8.56; 19/196, Oncology] 51. Hsu, T., Steeg, P. S., Zollo, M. and Wieland, T (2015) Progress on Nme (NDP kinase/Nm23/Awd) gene family-related functions derived from animal model systems: studies on development, cardiovascular disease, and cancer metastasis exemplified (Editorial) Naunyn-Schmiedeberg Arch. Pharm. 388: 109-117. [IF: 2.38; 204/773, Pharmacology] 52. Kirschner, R, Hsu, T., Tuan, N.N., Chen, C.L. and Huang, S.L. (2015) Characterization of Fungal and Bacterial Components in Gut/Fecal Microbiome. Curr. Drug Metab. 16: 272-283. [IF: 2.98; 82/254 Pharmacology] 53. Romani, P., Papi, A., Ignesti, M., Soccolini, G., Hsu, T., Gargiulo, G., Spisni, E., and Cavaliere, V. (2016) Dynamin controls extracellular level of Awd/Nme1 metastasis suppressor protein. Naunyn-Schmiedeberg Arch. Pharm. 389: 1171-1182. [IF: 2.38; 204/773, Pharmacology] 54. Bader, H.L.† and Hsu, T. (2016) Inactivation of the tumor suppressor gene von Hippel-Lindau (VHL) in granulocytes contributes to development of liver hemangiomas in a mouse model. BMC Cancer. 16: 797. [IF: 3.36; 63/322, Oncology] 55. Kuo, C.Y.,† Lin, C.H.,# and Hsu, T. (2017) VHL inactivation in precancerous kidney cells induces an inflammatory response via ER stress-activated IRE1α signaling. Cancer Research. 77: 3406-3416. [9.12; 9/344, Oncology] [This paper won the Ministry of Science and Technology, Taiwan, Outstanding Postdoctoral Research Paper Award, 2017]. 56. Huang, H.-Y., Hsu, T. and Lin, B.F. (2017) gamma-Aminobutyric acid alleviates progression of renal inflammation and injury in the Vhlh gene-knockout mice: Tu-P14-28. Cytokine. 100: 185-186. [IF: 3.08; 107/446, Biochemistry] 57. Romani, P., Ignesti, M., Gargiulo, G., Hsu, T. (co-corresponding), and Cavaliere, V. (2018) Extracellular NME proteins: a player or a bystander? Lab. Invest. 98:248-257. [IF: 4.86; 16/128 Medicine, Research and Experimental] 58. Chen, H.Y., Hsiao, Y.T., Liu, S.C.,† Hsu, T., Woon, W.Y., and I, L. (2018) Enhancing Cancer Cell Collective Motion and Speeding up Confluent Endothelial Dynamics through Cancer Cell Invasion and Aggregation. Physical Rev. Lett. 121:018101. [IF: 8.84; 7/268, Physics and Astronomy] 59. Liu, S.C., Hsu, T., Chang, Y.S., Chung, A.K., Jiang, S.S, OuYang, C.N., Hsueh, C., Liu, Y.P., Yuh, C.H., and Tsang, N.M. (2018) Cytoplasmic LIF reprograms invasive mode to enhance NPC dissemination through YAP1-FAK/PXN signaling. Nature Communications. 9: 5105. [IF: 12.35; 3/64, Multidisciplinary Sciences] 60. Huang, H.-Y., Hsu, T., and Lin, B.F. (2019) Gamma-aminobutyric acid decreases macrophages infiltration and suppresses inflammatory responses in renal injury. J. Functional Food. 60: 103419. [IF: 3.78; 37/206; Medicine (miscellaneous)] 61. Mezzofanti, E., Ignesti, M., Hsu, T., Gargiulo, G., and Cavaliere, V. (2019) Vps28 is involved in the intracellular trafficking of Awd, the Drosophila homologue of NME1/2. Frontiers Physiol. 10: 983. [IF: 4.13; 47/167, Physiology] 62. Tseng, C.-H., Lin, C., Chang, H.-C., Liu, C.-C., Serafico, B.M.F., Wu, L.-C., Lin, C.-T., Hsu, T., Huang, C.-Y., and Lo, M.-T. (2019) A Real-World Implementation of Cloud-Based AI System for Large-Scale Arrhythmia Screening. IEEE Computer. 52: 40-51. [IF: 3.56; 12/107; Computer Science, software engineering] 63. Hsu, T., Nguyen-Tran, Hieu-Huy #, and Trojanowska, M.E. (2019) Active roles of dysfunctional vascular endothelium in fibrosis and cancer. J. Biomed. Sci. 26: 86. [Invited review] [IF: 5.20; 80/277, Cancer Research] 64. Nguyen-Tran, H.-H.# and Hsu, T. (2020) Endothelial cell activation in the conditional Vhlh knockout kidney through oncostatin M pathway. Cancer Immunol. Res. (3 Supplement) A99-A99. 65. Nguyen, T.-N.# and Hsu, T. (2020) VHL inactivated kidney epithelial cells reprogram macrophage behavior through IL-6 and CXCL-1 secretion. Cancer Immunol. Res. (3 Supplement) B92-B92. 66. Chen, C.-Y., Lee, D.S., Choong, O.K., Chang, S.-K., Hsu, T., Nicholson, M.W., Liu, L.-W., Lin, P.-J., Ruan, S.-C., Lin, S.-W., Hu, C.-Y. and Hsieh, P.C.H. (2021) Cardiac-specific MicroRNA-125b deficiency induces perinatal death and cardiac hypertrophy. Sci. Rep. 11:2377. [IF: 4.149; 10/135, Multidisciplinary 10/135] 67. Pan, S.-Y., Tsai, P.-Z., Chou, Y.-H., Chang, Y.-T., Chang, F.-C., Chiu, Y.-L., Chiang, W.-C., Hsu, T., Wu, M.-., Chen, Y.-M., Chu, T.-S., and Lin, S.-L. (2021) Kidney pericyte hypoxia-inducible factor regulates erythropoiesis but not kidney fibrosis. Kidney International 99: 1354–1368. [IF: 8.945; 3/66 Medicine-Nephrology] 68. Nguyen-Tran, H.-H., # Nguyen, T.-N., # Chen, C.-Y. † and Hsu, T. (2021). Endothelial reprograming stimulated by oncostatin M promotes inflammation and tumorigenesis in VHL-deficient kidney tissue. Cancer Res. 81: 5060-5073. [IF: 12.7; 16/211, Cancer Research] 69. Kuo, C.Y., Chiu, V., Hsieh, P.C., Hsu, T. and Lin, T.-Y. (2021) Loss of function of von Hippel-Lindau triggers lipocalin 2-dependent inflammatory responses in cultured and primary renal tubular cells. Oxidative Medicine and Cellular Longevity 2021: 5571638. [IF: 5.076; 10/35, Aging]

醫學院生物醫學研究所 講座教授／Graduate Institute of Biomedical Sciences Chair Professor

基本資料/Profiles

學歷/Education

  • 南卡羅來納大 分子生物 博士

經歷/Work experience

  • 中國醫藥大學 生物醫學研究所 講座教授(1100801~)
    China Medical University Graduate Institute of Biomedical Sciences Chair Professor
  • 中國醫藥大學 教授(1100801~)
  • 國立中央大學 教授(1020801~1100731)
  • 波士頓大學醫學院 Professor(0981001~1020423)
  • Medical University of South Carolina, Professor(0950701~0980930)
  • Medical University of South Carolina, Associate Professor(0880701~0950630)
  • Medical University of South Carolina, Assistant Professor(0821201~0880630)

主管經歷/Administrative experience

專長/Research expertise

  • 癌症生物學 / Cancer biology
  • 免疫學 / Immunology
  • 細胞與胚胎發育學 / Cell and developmental biology
  • 研究組織發炎與癌症發生之關係。 / Study of relationship between inflammation and cancer progression