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易威伸博士

理学院
化学系助理教授

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易威伸博士

联络

简历

Dr Aik Wei-shen is interested in studying protein-nucleic acid complexes in various contexts, such as RNA metabolism, viral replication and cancer. He also aspires to be innovative in designing therapies using structures of protein/nucleic acid complexes as guides. The core technique is macromolecular X-ray crystallography. Dr Aik is also interested in using other structural biology tools such as cryo-electron microscopy to obtain the structural information of macromolecules. He takes advantage of powerful techniques in chemistry to detect, analyse and probe biomolecules. Examples of techniques frequently used are mass spectrometry and liquid chromatography. He also incorporates molecular biology techniques into his research.

 

项目介绍

FTO-inhibitor structures

FTO-inhibitor structures

ALKBH5 model

ALKBH5 model

成就

  • RGC Early Career Scheme (2019-20)

 

出版

  • Sun, Yadong, Yixiao Zhang, Wei-shen Aik, Xiaocui Yang, William F. Marzluff, Thomas Walz, Zbigniew Dominski & Tong Liang. “Structure of an active human histone pre-mRNA 3’-end processing machinery.” Science 367.6478 (2020): 700-703. https://science.sciencemag.org/content/367/6478/700
  • Bucholc, Katarzyna, Wei-shen Aik, Xiaocui Yang, Kaituo Wang, Z. Hong Zhou, Michał Dadlez, William F. Marzluff, Tong Liang & Zbigniew Dominski. “Composition and processing activity of a semi-recombinant holo U7 snRNP.” Nucleic Acids Research 48.3 (2020): 1508-1530. https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkz1148/5670844
  • Aik, Wei-shen, Min-han Lin, Dazhi Tan, Ashutosh Tripathy, William F. Marzluff, Zbigniew Dominski, Chi-yuan Chou & Tong Liang. “The N-terminal domains of FLASH and Lsm11 form a 2:1 heterotrimer for histone pre-mRNA 3’-end processing.” PLoS ONE 12.10 (2017), art. no. e0186034. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186034
  • Horita, Shoichiro, John S. Scotti, Cyrille Thinnes, Yousef S. Mottaghi-Taromsari, Armin Thalhammer, Wei Ge, Wei-shen Aik, Christoph Loenarz, Christopher J. Schofield & Michael A. McDonough. “Structure of the ribosomal oxygenase OGFOD1 provides insights into the regio- and stereoselectivity of prolyl hydroxylases.” Structure 23.4 (2015): 639-652. http://www.sciencedirect.com/science/article/pii/S0969212615000386
  • McMurray, Fiona, Marina Demetriades, Wei-shen Aik, Myrte Merkestein, Holger Kramer, Daniel S. Andrew, Cheryl L. Scudamore, Tertius A. Hough, Sara Wells, Frances M. Ashcroft, Michael A. McDonough, Christopher J. Schofield & Roger D. Cox. “Pharmacological inhibition of FTO.” PLoS ONE 10.4 (2015): e0121829. http://dx.plos.org/10.1371/journal.pone.0121829
  • Aik, Wei-shen, Rasheduzzaman Chowdhury, Ian J. Clifton, Richard J. Hopkinson, Thomas Leissing, Michael A. McDonough, Radosław Nowak, Christopher J. Schofield & Louise J. Walport. “Introduction to structural studies on 2-oxoglutarate-dependent oxygenases and related enzymes.” RSC Metallobiology 3 (2015): 59-94. https://pubs.rsc.org/--/content/chapter/bk9781849739504-00059/978-1-84973-950-4
  • Scotti, John S., Ivanhoe K. H. Leung, Wei Ge, Michael A. Bentley, Jordi Paps, Holger B. Kramer, Joongoo Lee, Wei-shen Aik, Hwanho Choi, Steinar M. Paulsen, Lesley A. H. Bowman, Nikita D. Loik, Shoichiro Horita, Chia-hua Ho, Nadia J. Kershaw, Christoph M. Tang, Timothy D. W. Claridge, Gail M. Preston, Michael A. McDonough & Christopher J. Schofield. “Human oxygen sensing may have origins in prokaryotic elongation factor Tu prolyl-hydroxylation.” Proceedings of the National Academy of Sciences of the United States of America 111.37 (2014): 13331-13336. http://www.pnas.org/content/111/37/13331.short
  • Xu, Chao, Ke Liu, Wolfram Tempel, Marina Demetriades, Wei-shen Aik, Christopher J. Schofield & Jinrong Min. “Structures of human ALKBH5 demethylase reveal a unique binding mode for specific single-stranded N6-methyladenosine RNA demethylation.” Journal of Biological Chemistry 289.25 (2014): 17299-17311. http://www.jbc.org/content/early/2014/04/28/jbc.M114.550350.1.short
  • Aik, Wei-shen, John S. Scotti, Hwanho Choi, Lingzhi Gong, Marina Demetriades, Christopher J. Schofield, Michael A. McDonough. “Structure of human RNA N6-methyladenine demethylase ALKBH5 provides insights into its mechanisms of nucleic acid recognition and demethylation.” Nucleic Acids Research 42.7 (2014): 4741-4754. http://nar.oxfordjournals.org/content/42/7/4741.short
  • Brem, Jürgen, Sander S. van Berkel, Wei-shen Aik, Anna Maria Rydzik, Matthew B. Avison, Ilaria Pettinati, Klaus-Daniel Umland, Akane Kawamura, James Spencer, Timothy D. W. Claridge, Michael A. McDonough & Christopher J. Schofield. “Rhodanine hydrolysis leads to potent thioenolate mediated metallo-β 2-lactamase inhibition.” Nature Chemistry 6.12 (2014): 1084-1090. http://www.nature.com/nchem/journal/v6/n12/abs/nchem.2110.html
  • Hopkinson, Richard J., Anthony Tumber, Clarence Yapp, Rasheduzzaman Chowdhury, Wei-shen Aik, Ka-hing Che, Xuan Shirley Li, Jan B. L. Kristensen, Oliver N. F. King, Mun Chiang Chan, Kar Kheng Yeoh, Hwanho Choi, Louise J. Walport, Cyrille C. Thinnes, Jacob T. Bush, Clarisse Lejeune, Anna M. Rydzik, Nathan R. Rose, Eleanor A. Bagg, Michael A. McDonough, Tobias J. Krojer, Wyatt W. Yue, Stanley S. Ng, Lars Olsen, Paul E. Brennan, Udo Oppermann, Susanne Müller, Robert J. Klose, Peter J. Ratcliffe, Christopher J. Schofield & Akane Kawamura. “5-Carboxy-8-hydroxyquinoline is a broad spectrum 2-oxoglutarate oxygenase inhibitor which causes iron translocation.” Chemical Science 4.8 (2013): 3110-3117. http://pubs.rsc.org/en/Content/ArticleLanding/2013/SC/c3sc51122g#!divAbstract
  • Aik, Wei-shen, Marina Demetriades, Muhammad K. K. Hamdan, Eleanor A. L. Bagg, Kar Kheng Yeoh, Clarisse Lejeune, Zhihong Zhang, Michael A. McDonough & Christopher J. Schofield. “Structural basis for inhibition of the fat mass and obesity associated protein (FTO).” Journal of Medicinal Chemistry 56.9 (2013): 3680-3688. http://pubs.acs.org/doi/abs/10.1021/jm400193d
  • Aik, Wei-shen, Michael A. McDonough, Armin Thalhammer, Rashed Chowdhury & Christopher J. Schofield. “Role of the jelly-roll fold in substrate binding by 2-oxoglutarate oxygenases.” Current Opinion in Structural Biology 22.6 (2012): 691-700. http://www.sciencedirect.com/science/article/pii/S0959440X12001595
  • Woon, Esther C. Y., Marina Demetriades, Eleanor A. L. Bagg, Wei-shen Aik, Svetlana M. Krylova, Jerome H. Y. Ma, Munchiang Chan, Louise J. Walport, David W. Wegman, Kevin N. Dack, Michael A. McDonough, Sergey N. Krylov & Christopher J. Schofield. “Dynamic combinatorial mass spectrometry leads to inhibitors of a 2-oxoglutarate-dependent nucleic acid demethylase.” Journal of Medicinal Chemistry 55.5 (2012): 2173-2184. http://pubs.acs.org/doi/abs/10.1021/jm201417e
  • Thalhammer, Armin, Wei-shen Aik, Eleanor A. L. Bagg & Christopher J. Schofield. “The potential of 2-oxoglutarate oxygenases acting on nucleic acids as therapeutic targets.” Drug Discovery Today: Therapeutic Strategies, 9.2-3 (2012): e91-e100. http://www.sciencedirect.com/science/article/pii/S1740677312000083

 

专访

投身科研改善人类健康

Dr Aik

 

【「人才100」系列文章】

 

骤眼看来，化学系助理教授易威伸博士位於查济民科学大楼的实验室，与一般标准的化学实验室无异，同样布置着各类仪器，以及盛载不同化学物品与溶液的玻璃容器。事实上，这是一所结合化学与生物化学的研究实验室，在设备簇新、光鲜明亮的环境中，这位年轻科学家与他的团队正埋首拆解一个重要却又复杂的问题：如何帮助人类减少疾病痛苦。研究团队目前展开有关分子抑制剂的研究，希望未来能找出治疗癌症的新方法。

 

人体内的核醣核酸（Ribonucleic Acid，简称RNA）是一种生物分子，在基因表达与调节等过程中发挥重要作用，而核醣核酸化学修饰对修饰及调控其功能至关重要。当一些用於修饰核醣核酸的酵素出现异常活动或突变时，则有可能诱发癌症。为了验证抑制酵素是否能够实现抗癌作用，易博士的团队采用结合化学生物学和结构生物学的方法，透过X射线晶体学，分析原子级抑制剂的结合模式。团队运用所得的结构数据，进一步了解疾病的起源，以研发能控制肿瘤生长的抑制剂为长远目标。

 

这项目获得研究资助局的2019 / 20年度「杰出青年学者计划」拨款，初步的研究结果发现了具有发展潜力的分子。易博士认为，能够建立良好的研究基础对於新进学者十分重要。他说：「我们会根据所取得的蛋白晶体结构资料，设计下一代抑制剂，有助於将来研制更有效的药物。」

 

 

创新方案解决健康问题

 

来自马来西亚的易博士投身疾病成因与治疗的研究，全因他从小对这方面充满兴趣。为了解人类健康的奥秘，并找出疾病的治疗方法，他取得奖学金后到英国剑桥大学修读生物化学。他说：「那时候我发现要更有效地研发出疾病疗法，必需要对化学和蛋白质与分子结构有更深入的认识。」

 

他遂循化学生物学和结构生物学发展，先后於剑桥大学与牛津大学取得生物化学硕士与化学生物学博士学位。他其后在纽约哥伦比亚大学进行博士后研究，运用冷冻电子显微术等结构生物学研究技术，观察大分子的结构。他目前在浸大进行多项研究项目，均有采用化学生物学和结构生物学技术。

 

推动科研发展的学术环境

 

对知识的不断渴求，驱使这位青年学者於2019年初来港发展，透过「人才100」计划加入浸大。大学早前推行「人才100」计划，招募来自世界各地不同领域的优秀教研人员。

 

对易博士来说，浸大在科研发展上提供不少机遇，成为他来港工作的原因之一。他说：「浸大提供优良的资源和设备，反映大学决心推动跨学科研究，营造合适的氛围环境，促进崭新研究及创新。」

 

同侪互相支持的校园文化，亦有助易博士迅速适应新的工作环境。他重视与校内其他学者互相交流的机会，就研究题目分享心得。最令他欣喜的是，能够与主动和积极的团队共事。他表示：「团队间的合作和支持令这里的研究工作十分愉快。」