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Dr Wei-shen Aik

Assistant Professor
Department of Chemistry
Faculty of Science

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Dr Wei-shen Aik

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About

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.

 

Highlights

FTO-inhibitor structures

FTO-inhibitor structures

ALKBH5 model

ALKBH5 model

Achievements

  • RGC Early Career Scheme (2019-20)

 

Research Outputs

  • 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

 

Feature

A quest to improve human health

Dr Aik

 

This story is part of a series about the Talent100 initiative.

 

At first glance, Dr Aik Wei-shen's lab looks like any standard chemistry lab with various pieces of equipment and shelves of glassware holding chemicals and liquids. In fact, the lab is a hybrid of chemistry and biochemistry, and a relatively new one in the Cha Chi-ming Science Tower, which seems fitting for the young scientist. Within those brightly-lit walls, Dr Aik, Assistant Professor of the Department of Chemistry, and his team investigate an exciting yet perplexing problem: how to reduce human suffering, and in particular, how to develop molecules that have potential anti-cancer properties.

 

Chemical modifications play an important role in modifying and regulating the function of ribonucleic acid (RNA), a biological molecule that plays a vital role in the expression and regulation of genes in the body. However, dysregulation and mutations in several RNA-modifying enzymes have been associated with various types of cancer. In an interdisciplinary approach merging chemical and structural biology, the HKBU team led by Dr Aik studies the potential anti-cancer effects of small molecule inhibitors by using macromolecular X-ray crystallography to understand the binding modes of inhibitors at the atomic level. The researchers then take the three-dimensional structural information as a guide to understanding diseases, with the ultimate goal of developing inhibitors which can suppress the progression of tumours.

 

The project has received funding under the Research Grants Council's Early Career Scheme 2019/20, and the team has already obtained preliminary findings that offer a glimpse of potential molecules. Dr Aik believes that it is important for early career scientists to establish a foundation in their fields of research. "We are looking into identifying tools based on the structures of protein-drug complexes. Then we can build on this knowledge to design better drugs," he says.

 

Designing new solutions to health problems

 

When Dr Aik was growing up in Malaysia, he was always curious about what causes diseases and what can cure them. Motivated by the wish to understand the complexities of human health issues and finding solutions to reduce suffering, he studied Biochemistry at the University of Cambridge on a scholarship. "During my studies, I realised that in order to develop treatments more effectively, it is important for me to understand chemistry as well as the structure of proteins and molecules," he says of his academic journey of studying chemical biology and structural biology.

 

He has been moving in that direction ever since, earning a master's degree in Biochemistry at the University of Cambridge and a doctoral degree in Chemical Biology from the University of Oxford. He then conducted postdoctoral work at Columbia University in New York, where he gained experience of using structural biology techniques, such as cryo-electron microscopy, to obtain the structural information of macromolecules. Now in his own lab at HKBU, he has been incorporating chemical biology and structural biology techniques into his research projects.

 

A supportive environment for research

 

This relentless pursuit of knowledge brought the early-career researcher to Hong Kong in early 2019, when he joined HKBU as a faculty member under the University's Talent100 initiative, which was a recruitment campaign launched to attract top global talent from diverse disciplines.

 

For Dr Aik, research opportunities were one of the important factors he considered when he decided to make the move. "The support and resources provided by HKBU are indicative of the University's commitment to fostering interdisciplinary research collaborations. This enabling environment is important in promoting science and innovation," he says.

 

A culture of peer support also helped him feel quickly at home in his new position. Members of the faculty often meet and share ideas on research topics, and Dr Aik highly values these exchanges. Most of all, he appreciates how motivated his research team is. "Having people you can count on for help and support makes my experience here positive," he says.