Tien Hsu

Professor

Education:

PhD, Medical University of South Carolina

Postdoc, Harvard University

General field of research:

Tumor suppressor gene functions in development

Affiliations other than medicine:

Evans Center for Interdisciplinary Biomedical Research
Hematology/Oncology

Contact information:

Office
650 Albany St. EBRC 445

tienh@bu.edu

Keywords:

VHL tumor suppressor gene; Epithelial morphogenesis; Nm23 metastasis suppressor gene; Drosophila; kidney cancer

Summary of research interest:

The Drosophila (fruit fly) and knockout mouse systems are employed to study the functions of tumor suppressor gene VHL and anti-metastasis gene Nm23.

VHL (von Hippel-Lindau disease) gene mutations specifically cause renal cell carcinoma, hemangioblastoma (over-growth of blood vessels in the central nervous system), and a few other minor tumors.  VHL protein has been shown to function as an ubiquitin ligase that targets such proteins as hypoxia-inducible factor (HIF). We have demonstrated that VHL mutations in Drosophila and in human cancer cells resulted in defective endocytosis of growth factor receptors, FGFR in particular.  This endocytic function is at least in part mediated by the anti-metastasis gene Nm23.  Nm23 encodes a nucleoside diphosphate kinase that is potentially a GTP supplier for cellular GTPases.  We showed that in Drosophila, Nm23 gene (named awd in flies) promotes the activity of early endosomal factor Rab5.  The endocytic functions of these genes also contribute to their roles in establishing and maintaining epithelial integrity.

We are currently utilizing mouse models and primary cell cultures to analyze their molecular activities, and establish the mechanisms of tumorigenesis and angiogenesis in the mutants of these important gene functions.

hsu_vhl-fgfr1 hsu_st9-egg1

Selected Publications:

(#: Student; †: postdoc)

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. [Abstract] [Full text]

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. [Abstract] [Full text]

Adereth, Y.#, Dammai, V., Kose, N., Li, R. and Hsu, T. (2005) RNA-dependent integrin a3 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] [Abstract] [Full text]

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. [Abstract] [Full text]

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] [Abstract] [Full text]

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. [Abstract] [Full text]

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. [Abstract] [Full text]

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. [Abstract] [Full text]

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. [Abstract] [Full text]

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. [Abstract] [Full text]

Mahajan, S., Dammai, V., Hsu. T. and Kraft, A.S. (2008) Hypoxia-inducible factor-2a regulates the expression of TRAIL receptor DR5 in renal cancer cells.  Carcinogenesis 29: 1734-1741. [Abstract] [Full text]

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

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] [Abstract] [Request for pdf]

Technologies available for sharing upon request:

Drosophila genetics; 3D coculture of endothelial cells and cancer cells; 3D ascinus formation; kidney tubule cell isolation