报告时间：2017年4月20日上午9:00
报告地点：科技创新大楼C501室
报告题目：Molecular imaging and killing of latently EBV-infected tumor cells by the development of EBNA1 responsive bioprobes

Molecular imaging and killing of latently EBV-infected tumor cells by the development of EBNA1 responsive bioprobes

Ka-Leung Wong
Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong

Epstein-Barr virus (EBV) is etiologically implicated in several lymphoid and epithelial malignancies, substantially contributing to the development of a diversity of lymphomas and carcinomas. Such presence of EBV in the tumor cells of EBV-associated cancers can, therefore, provide overarching basis for specific therapy.

Although current treatments for EBV-associated carcinoma, such as radiotherapy and chemotherapy have long been adopted, the former is inadequate either to kill advanced, metastatic tumor or to prevent their recurrence, while the latter is still under development. The dimeric viral oncoprotein, Epstein-Barr nuclear antigen (EBNA1), is known to be responsible for the development of EBV-related malignancies and the maintenance of EBV episome. Given that carcinogenesis of EPV-associated carcinoma is symbiotically connected with EBV infection and EBNA1 can function (e.g. replication, DNA binding and transactivation) only upon dimerization (formation of the active form), we hypothesize that a fluorescent probe consisting of a chromophore and an EBNA1-specific molecule which hampers the dimer formation can be used for the imaging and inhibition of latent EBV-infected cells.

In this seminar, I m are going to show some of our progress in the development of responsive bioprobes for inhibition of EBNA1 dimerization. Our study are provided a novel strategy to interfere the growth of EBV-associated tumor cells. All our europium complexes are all water-soluble and cell-permeable for EBNA1 in vitro imaging and inhibition. We hope our work here can bring to society a more powerful tool (especially able to combine multi-photon and time-resolved technology) to unveil the mystery and understand the very role of EBNA1 in EPV-associated carcinoma for further cancer therapy and research.

Reference:
1. L. Jiang, R. Lan, T. Huang, C.-F. Chan, H. Li, S. Lear, J. Zong, W.-Y. Wong, M. M.-Lan Lee, B. D. Chan, W.-L. Chan, W.-S. Lo, N.-K. Mak,* M. L. Lung, G. S. Taylor, Z.-X. Bian, W. C. S. Tai, G.-L. Law,* W.-T. Wong,* S. L. Cobb,* and K.-L. Wong,* ‘Targeting EBNA1: A therapeutic approach for EBV-related tumour with tailor responsive optical imaging’, Nature Biomedical Engineering, (2017) 0042.
2. L. Jiang, L.-L. Lau, H. Li, C.-F. Chan, R. Lan, W.-L. Chan, T. C.-K. Lau, G. S.-W. Tsao, N.-K. Mak and K.-L. Wong,* ‘EBNA1 specific luminescence small molecules for imaging and inhibition of latently EBV-infected tumor cells’, Chemical Communications, 50 (2014) 6517-6519.