Research


Molecular Mechanism of Oncogenesis

Dr. DY Jin

Professor Jin, Dong-Yan (金冬雁)

Professor, Department of Biochemistry

BSc (Sun Yatsen University); PhD (PUMC Beijing)

Contact
Email: dyjin@hku.hk
Tel: (852) 2819 9491 (Office); 2819 2812 (Lab)
Office: L3-65, Laboratory Block, 21 Sassoon Road, Hong Kong
Awards and Distinctions
Leukemia and Lymphoma Society Scholar (2001-2006)
Outstanding Researcher Award, HKU (2008)

Postgraduate Research Projects Available:

  • Molecular mechanism of viral oncogenesis
  • Molecular mechanism of innate antiviral immunity

Research Description:

Research in our laboratory is focused primarily on the molecular basis of viral oncogenesis and virus-host interaction. We use a combination of biochemical and genetic approaches to conduct basic research in molecular virology and oncology with the aim to apply the knowledge gained to medicine. Areas of special current interest include: 1) cellular targets of viral oncoproteins and oncomirs, 2) genome instability, and 3) innate antiviral immunity. In connection to these three major areas of research, our interests also extend to other general aspects of molecular cell biology, including transcriptional and translational regulation, post-translational protein modifications, cell cycle checkpoints, centrosome, unfolded protein response and virus-cell interaction.

In our study of human T-cell leukemia virus type I oncoprotein Tax, we identified a cellular protein named MAD1, a key component of the mitotic checkpoint (Jin et al., 1998). We also characterized another centrosomal target of Tax protein that might contribute to the development of aneuploidy in leukemic cells (Ching et al., 2006). Our future work will ask whether and how cellular protein kinases might modulate the activity of Tax. Our investigations on Epstein-Barr virus revealed a new mechanism in which a viral microRNA targets a cellular proapoptotic protein to promote the survival of tumor cells (Choy et al., 2008). Our next goal is to define the roles of Epstein-Barr virus-encoded microRNAs in viral persistence and transformation of epithelial cells. More recently, we found that the cytoplasmic virus sensor RIG-I needs a double-stranded RNA-binding protein partner called PACT to initiate and sustain innate antiviral response (Kok et al., 2011). We will expand our analysis to derive a mechanistic understanding of how PACT interacts with viral RNA to activate RIG-I-like sensors. Additionally, we endeavor to translate our new findings into new targets and strategies in the prevention and control of viral diseases and cancer.

Our research projects are funded by grants from the Hong Kong Research Grants Council (RGC), the Research Fund for the Control of Infectious Diseases (RFCID), and S.K. Yee Medical Foundation.

Lab of DY Jin

Publications, Achievements, and Grants:

Selected Publications:

  • Kok, K.-H., Lui, P.-Y., Ng, M.-H.J., Siu, K.-L., Au, S.W.N. and Jin, D.-Y. The double-stranded RNA-binding protein PACT functions as a cellular activator of RIG-I to facilitate innate antiviral response. Cell Host Microbe, 9: 299-309, 2011 (http://www.cell.com/cell-host-microbe/abstract/S1931-3128(11)00094-1)
  • Chan, C.-P., Mak, T.-Y., Chin, K.-T., Ng, I. O.-L. and Jin, D.-Y. N-linked glycosylation is required for optimal proteolytic activation of membrane-bound transcription factor CREB-H. J. Cell Sci., 123: 1438-1448, 2010 (http://jcs.biologists.org/content/123/9/1438.long)
  • Tang, H.-M.V., Siu, K.-L., Wong, C.-M. and Jin, D.-Y. Loss of yeast peroxiredoxin Tsa1p induces genome instability through activation of DNA damage checkpoint and elevation of dNTP levels. PLoS Genet., 5: e1000697,2009 (http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1000697 )
  • Choy, E.Y.-W., Siu, K.-L., Kok, K.-H., Lung, R.W.-M., Tsang, C.M., To, K.-F., Kwong, D.L.-W., Tsao, S.W. and Jin, D.-Y. An Epstein-Barr virus-encoded microRNA targets PUMA to promote host cell survival. J. Exp. Med., 205: 2551-2560, 2008 (http://jem.rupress.org/cgi/content/full/205/11/2551)
  • Chin, K.-T., Chun, A.C.S., Ching, Y.-P., Jeang, K.-T. and Jin, D.-Y. (2007) Human T-cell leukemia virus oncoprotein represses nuclear receptor-dependent transcription by targeting coactivator TAX1BP1. Cancer Res., 67: 1072-1081 (http://cancerres.aacrjournals.org/cgi/content/full/67/3/1072)
  • Ching, Y.-P., Chan, S.-F., Jeang, K.-T. and Jin, D.-Y. (2006) Retroviral oncoprotein Tax targets the coiled-coil centrosomal protein TAX1BP2 to induce centrosome overduplication. Nat. Cell Biol., 8: 717-724 (http://www.nature.com/ncb/journal/v8/n7/abs/ncb1432.html)
  • Chan, C.-P., Siu, K.-L., Chin, K.-T., Yuen, K.-Y., Zheng, B. and Jin, D.-Y. (2006) Modulation of the unfolded protein response by severe acute respiratory syndrome coronavirus spike protein. J. Virol., 80: 9279-9287 (http://jvi.asm.org/cgi/content/full/80/18/9279)
  • Chin, K.-T., Zhou, H.-J., Wong, C.-M., Lee, J.M.-F., Chan, C.-P., Qiang, B.-Q., Yuan, J.-G., Ng, I.O.-L. and Jin, D.-Y. (2005) The liver-enriched transcription factor CREB-H is a growth suppressor protein underexpressed in hepatocellular carcinoma. Nucl. Acids Res., 33: 1859-1873 (http://nar.oxfordjournals.org/cgi/content/full/33/6/1859)
  • Wong, C.-M., Zhou, Y., Ng, R.W.M., Kung, H.-F. and Jin, D.-Y. (2002) Cooperation of yeast peroxiredoxins Tsa1p and Tsa2p in the cellular defense against oxidative and nitrosative stress. J. Biol. Chem., 277: 5385-5394 (http://www.jbc.org/content/277/7/5385.long)
  • Jin, D.-Y., Wang, H.-L., Zhou, Y., Chun, A.C.S., Kibler, K.V., Hou, Y.-D., Kung, H.-f., and Jeang, K.-T. (2000) Hepatitis C virus core protein-induced loss of LZIP function correlates with cellular transformation. EMBO J., 19: 729-740 (http://www.nature.com/emboj/journal/v19/n4/abs/7592184a.html)
  • Jin, D.-Y., Giordano, V., Kibler, K.V., Nakano, H. and Jeang, K.-T. (1999) Role of adapter function in oncoprotein-mediated activation of NF-κB: Human T-cell leukemia virus type I Tax interacts directl with IkB kinase γ. J. Biol. Chem., 274: 17402-17405 (http://www.jbc.org/content/274/25/17402.long)
  • Jin, D.-Y., Spencer, F. and Jeang,K.-T. (1998) Human T-cell leukemia virus type I oncoprotein Tax targets the human mitotic checkpoint protein MAD1. Cell, 93: 81-91 (http://www.cell.com/retrieve/pii/S0092867400811484)
  • Jin, D.-Y., Li, Z.-L., Jin, Q., Yuwen, H. and Hou, Y.-D. (1989) Vaccinia virus hemagglutinin: A novel member of the immunoglobulin superfamily. J. Exp. Med., 170: 571-576 (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2189399/pdf/je1702571.pdf)