中央大學系統生物與生物資訊研究所
Institute of Systems Biology and Bioinformatics
National Central University

CS_Chen 徐沺 (Tien Hsu, PhD)
Professor
University Chair Professor in Biomedicine
Taiwan Biodevelopment Foundation Chair Professor in Biotechnology

E-mail:  tienhsu @ncu.edu.tw  |  Lab. Room 503, S5-5F |  ext 36115
Office: Room 502, S5-5F  |  Tel: (03)4227151 ext 36108


Curriculum Vitae

  Bachelor, Department of Agricultural Chemistry, National Taiwan University, 1977-1981

  PhD, Medical University of South Carolina, USA, 1983-1988

  Postdoc, Department of Cellular and Developmental Biology, Harvard University, USA, 1989-1993

  Assistant Professor – Professor, Hollings Cancer Center, USA, 1993-2009

  Professor of Medicine, Boston University School of Medicine, 2009-2013

  Professor of Systems Biology and Bioinformatics, National Central University, Taiwan, 2013-present

  Dean, College of Heath Sciences and Technology, National Central University, Taiwan, 2014-present


Research Interest

1. Tumor microenvironment

2. Stromal biology of inflammation and cancer

3. The etiology of kidney disease and kidney cancer


  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 Chair of International Congress of NDPK/Nm23/awd Gene Family. He also served as grant review panel members of NIH (USA), NSF (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 over 40 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 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. His research team includes collaboration with international experts in cancer and in fibrotic diseases, which is a key aspect of tumor progression.

Normal epithelial tissues   Figure 1.
  (left one)

  Normal epithelial tissues have organized array of cells showing expression of polarity molecules such as E-cadherin and Lgl (green and red in A, respectively), and cortical microtubules (red in B). In contrast, cancer cells are fibroblastic with extensive microtubule network (green in C), or strong
  Figure 2.
  (right one)

  We are interested in how healthy tissues such as kidney (left) turn into malignant cancer (right). The transformation does not solely depend on genetic changes in the tumor cells; in large part the transformation also depends on the influence from microenvironment.
Transformation
Knockout mouse   Figure 3.
  (left one)

  Our laboratory uses animal model to study kidney cancer. For example, we knocked out a tumor suppressor gene named von Hippel-Lindau (VHL), which is very closely linked with renal cell carcinoma. The knockout mouse (right) appeared small.
  Figure 4.
  (right one)

  In the kidney, the knockout mouse shows transformed cells (lower panels) with abnormal nuclei and lipid-filled cytoplasm (clear cells); whereas wild-type (upper panels) kidney shows regular tubule arrangement.
Transformed cells
Knockout kidney   Figure 5.
  (left one)

  More importantly, the knockout kidney (B, C) shows extensive inflammation—infiltration of immune cells and distorted tubules, compared to wild-type (A). These results indicate that inflammation may be the precursor of cancer formation.



Lab. Members

Postdoctoral fellow Chan-yen Guo CS_Chen
Research assistant Yu-hui Shih CS_Chen
PhD Students Chih-hong Lin CS_Chen
Master Students Yuki Hagiwara,
(left)

Wei-cheng Fang
(right)
CS_Chen


Publications

Papers (since 2005):
(Hsu lab members in bold: undergraduate students¶; graduate students#; postdocs†)

  1. 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.

  2. 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.

  3. 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.

  4. 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]


  5. 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.


  6. 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]


  7. 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.


  8. 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.


  9. 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.


  10. 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.


  11. 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.


  12. 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.

  13. Nallamothu, G.†, Dammai, V. and Hsu, T. (2009) Developmental Function of Nm23/awd - A Mediator of Endocytosis. Mol. Cell. Biochm. 329: 35-44. [Review]

  14. 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]

  15. 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"]

  16. 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]

  17. Hsu, T. (2011) NME Genes in Epithelial Morphogenesis. Naunyn-Schmiedeberg Arch. Pharm. 384: 363-372. [Review]

  18. 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.

  19. Hsu, T. (2012) Complex cellular functions of the von Hippel-Lindau tumor suppressor gene: Insights from model organisms. Oncogene 31: 2247-2257. [Invited Review]

  20. Bader, H. L.† and Hsu, T. (2012) Systemic VHL gene functions and the VHL disease. FEBS Lett. 586:1562-1569. [Invited Review]

  21. Ignesti, M., Barraco, M., Nallamothu, G.†, Woolworth, J.A.#, Duchi, S., Gargiulo, G., Cavaliere, V. and Hsu, T. (2014) abnormal wing discs regulates Notch signaling in Drosophila. BMC Biology. 12:12.

  22. Lin, C.H.#, Dammai, V. Adryan, B. and Hsu, T. (2014) Interaction between Nm23 and the tumor supressor VHL. Naunyn-Schmiedeberg Arch. Pharm. Jun 12. [Epub ahead of print]

  23. Pritchett, T.L.†, Bader, H.L.†, Henderson, J. and Hsu, T. (2014) Conditional inactivation of the mouse von Hippel–Lindau tumor suppressor gene results in wide-spread hyperplastic, inflammatory, and fibrotic lesions in the kidney. Oncogene, Jul 14;0. doi: 10.1038/onc.2014.197.