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易威伸博士

理學院
化學系助理教授

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易威伸博士

聯絡

簡歷

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.

 

項目介紹

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

 

專訪

投身科研改善人類健康

Dr Aik

 

【「人才100」系列文章】

 

驟眼看來，化學系助理教授易威伸博士位於查濟民科學大樓的實驗室，與一般標準的化學實驗室無異，同樣佈置着各類儀器，以及盛載不同化學物品與溶液的玻璃容器。事實上，這是一所結合化學與生物化學的研究實驗室，在設備簇新、光鮮明亮的環境中，這位年輕科學家與他的團隊正埋首拆解一個重要卻又複雜的問題：如何幫助人類減少疾病痛苦。研究團隊目前展開有關分子抑制劑的研究，希望未來能找出治療癌症的新方法。

 

人體內的核醣核酸（Ribonucleic Acid，簡稱RNA）是一種生物分子，在基因表達與調節等過程中發揮重要作用，而核醣核酸化學修飾對修飾及調控其功能至關重要。當一些用於修飾核醣核酸的酵素出現異常活動或突變時，則有可能誘發癌症。為了驗證抑制酵素是否能夠實現抗癌作用，易博士的團隊採用結合化學生物學和結構生物學的方法，透過X射線晶體學，分析原子級抑制劑的結合模式。團隊運用所得的結構數據，進一步了解疾病的起源，以研發能控制腫瘤生長的抑制劑為長遠目標。

 

這項目獲得研究資助局的2019 / 20年度「傑出青年學者計劃」撥款，初步的研究結果發現了具有發展潛力的分子。易博士認為，能夠建立良好的研究基礎對於新進學者十分重要。他說：「我們會根據所取得的蛋白晶體結構資料，設計下一代抑制劑，有助於將來研製更有效的藥物。」

 

 

創新方案解決健康問題

 

來自馬來西亞的易博士投身疾病成因與治療的研究，全因他從小對這方面充滿興趣。為了解人類健康的奧秘，並找出疾病的治療方法，他取得獎學金後到英國劍橋大學修讀生物化學。他說：「那時候我發現要更有效地研發出疾病療法，必需要對化學和蛋白質與分子結構有更深入的認識。」

 

他遂循化學生物學和結構生物學發展，先後於劍橋大學與牛津大學取得生物化學碩士與化學生物學博士學位。他其後在紐約哥倫比亞大學進行博士後研究，運用冷凍電子顯微術等結構生物學研究技術，觀察大分子的結構。他目前在浸大進行多項研究項目，均有採用化學生物學和結構生物學技術。

 

推動科研發展的學術環境

 

對知識的不斷渴求，驅使這位青年學者於2019年初來港發展，透過「人才100」計劃加入浸大。大學早前推行「人才100」計劃，招募來自世界各地不同領域的優秀教研人員。

 

對易博士來說，浸大在科研發展上提供不少機遇，成為他來港工作的原因之一。他說：「浸大提供優良的資源和設備，反映大學決心推動跨學科研究，營造合適的氛圍環境，促進嶄新研究及創新。」

 

同儕互相支持的校園文化，亦有助易博士迅速適應新的工作環境。他重視與校內其他學者互相交流的機會，就研究題目分享心得。最令他欣喜的是，能夠與主動和積極的團隊共事。他表示：「團隊間的合作和支持令這裡的研究工作十分愉快。」