Analytical Science & Technology (Metabolomics)

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DELIVERING POWERFUL INSIGHTS ON CELLULAR METABOLISM

In Metabolomics research group, we focus on the characterisation of biotherapeutics products by developing assays to understand biotherapeutics mode of action, and clinical translation. Through development of new analytical technologies, we can determine quality attributes of new modalities such as cell therapy, mRNA vaccines and cultured meats. We actively support the industry, academia and Institutes of Higher Learning (IHLs) through our work, while providing customised analytical methods to maximise project outcomes.

Focus Areas

  • Metabolite characterisation of biotherapeutics products and their manufacturing processes, ranging from monoclonal antibodies to new modalities, such as bispecifics, cell therapy, mRNA vaccines and cultured meat.
  • Development of new analytical technologies to determine quality attributes of new modalities
  • Guide cell line engineering, bioprocess and media design through omics approach
  • Customized analytical method development for supporting industrial and academic partners for needs ranging from determining Critical Quality Attributes (CQAs), Critical Process Parameters (CPPs), to understanding biotherapeutics mechanisms of action and developing potency assays.


Our Capabilities

UNTARGETED METABOLOMICS

Untargeted Metabolomics

Global profiling of small molecules in biological samples to understand metabolic behaviour in different biological systems.
DETECTION AND IDENTIFICATION SHORT-CHAIN PEPTIDES

Detection and Identification of Short-Chain Peptides

Untargeted profiling of short-chain peptides in protein hydrolysates and culture media to serves as a basis of understanding the bioactivities and their benefit as serum alternatives.
TARGETED METABOLOMICS

Targeted Metabolomics

Absolute quantitation of specific metabolites of interest, for hypothesis-driven research and validation studies following untargeted profiling outcomes.
STABLE-ISOTOPE TRACING DESIGN COUPLED WITH LC-MS MS

STABLE-ISOTOPE TRACING DESIGN COUPLED WITH LC-MS/MS

This approach enables the in-depth study of how individual metabolites are consumed or produced in specific pathways of interest.
LC-MS AS A PLATFORM FOR DETERMINATION OF PRODUCT CRITICAL ATTRIBUTES

LC-MS AS A PLATFORM FOR DETERMINATION OF PRODUCT CRITICAL ATTRIBUTES

Example: 5’-cap structure, 5’-end capping efficiency, poly-A tail integrity as well as lipid nanoparticle composition for mRNA-based therapeutic products.
SAMPLE PREPARATION AUTOMATED WORKFLOWS

SAMPLE PREPARATION AUTOMATED WORKFLOWS

Automated sample preparation workflows to improve robustness and consistency of analysis.

Our Technologies

Untargeted Metabolomics and Stable Isotope Tracing Approach

Investigation of aberrant cellular metabolism for drug development models - Untargeted Metabolomics & Stable Isotope Tracing Approach

In partnership: Wang, Z., et al., Methionine is a metabolic dependency of tumor-initiating cells. Nat Med, 2019. 25(5): p. 825-837.

  • Untargeted Metabolomics: Global profiling of small molecules in biological samples to understand metabolic behaviour in different biological systems
  • Stable-isotope Tracing Design Coupled with LC-MS/MS enables the in-depth study of how individual metabolites are consumed or produced in specific pathways of interest

Targeted metabolomics

Investigation of aberrant cellular metabolism for drug development models - Targeted Metabolomics Approach

In partnership: Genetics of Exfoliation Syndrome, P., et al., Association of Rare CYP39A1 Variants With Exfoliation Syndrome Involving the Anterior Chamber of the Eye. JAMA, 2021. 325(8): p. 753-764.

  • Targeted Metabolomics: Absolute quantitation of specific metabolites of interest, for hypothesis-driven research and validation studies following untargeted profiling outcomes.

Detection and Identification of Short-Chain Peptides

Bioprocess Characterisation and Optimisation

  • Deep and well-established expertise in obtaining in-depth metabolite information on cell-based bioproduction processes for characterisation, leading to media design and bioprocess optimisation.
  • Detection and Identification of Short-Chain Peptides: Untargeted profiling of short-chain peptides in protein hydrolysates and culture media to serves as a basis of understanding the bioactivities and their benefit as serum alternatives

Characterisation of New Biotherapeutic Modalities

Characterisation of New Biotherapeutic Modalities

  • LC-MS as a Platform for Determination of Product Critical Quality Attributes (CQA)
    Example: 5’-cap structure, 5’-end capping efficiency, poly-A tail integrity as well as lipid nanoparticle composition for mRNA-based therapeutic products

Our Track Record

Featured Publications

  • Xun Hui Yeo, Vignesh Sundararajan, Zhengwei Wu, Zi Jin Cheryl Phua, Yin Ying Ho, Kai Lay Esther Peh, Yi-Chia Chiu, Tuan Zea Tan, Dennis Kappei, Ying Swan Ho, David Shao Peng Tan, Wai Leong Tam and Ruby Yun-Ju Huang (2023) The effect of inhibition of receptor tyrosine kinase AXL on DNA damage response in ovarian cancer. Communications Biology, 6(1): 660
  • Tram Anh Nguyen, Jia Wei Joel Heng, Pornchai Kaewsapsak, Eng Piew Louis Kok, Dominik Stanojević, Hao Liu, Angelysia Cardilla, Albert Praditya, Zirong Yi, Mingwan Lin, Jong Ghut Ashley Aw, Yin Ying Ho, Kai Lay Esther Peh, Yuanming Wang, Qixing Zhong, Jacki Heraud-Farlow, Shifeng Xue, Bruno Reversade, Carl Walkley, Ying Swan Ho, Mile Šikić, Yue Wan & Meng How Tan (2022) Direct identification of A-to-I editing sites with nanopore native RNA sequencing. Nature Methods 19(7): 833-844
  • Ian Walsh #, Matthew Myint #, Terry Nguyen-Khuong, Ying Swan Ho, Say Kong Ng and Meiyappan Lakshmanan (2022) Harnessing the potential of machine learning for advancing "Quality by Design" in biomanufacturing. mAbs 14(1): 2013593.
  • Genetics of Exfoliation Syndrome Partnership; Zheng Li, Zhenxun Wang, Mei Chin Lee, Matthias Zenkel, Esther Peh, Mineo Ozaki, Fotis Topouzis, Satoko Nakano, Anita Chan, Shuwen Chen, Susan E I Williams, Andrew Orr, Masakazu Nakano, Nino Kobakhidze, Tomasz Zarnowski, Alina Popa-Cherecheanu, Takanori Mizoguchi, Shin-Ichi Manabe, Ken Hayashi, Shigeyasu Kazama, Kenji Inoue, Yosai Mori, Kazunori Miyata, Kazuhisa Sugiyama, Tomomi Higashide, Etsuo Chihara, Ryuichi Ideta, Satoshi Ishiko, Akitoshi Yoshida, Kana Tokumo, Yoshiaki Kiuchi, Tsutomu Ohashi, Toshiya Sakurai, Takako Sugimoto, Hideki Chuman, Makoto Aihara, Masaru Inatani, Kazuhiko Mori, Yoko Ikeda, Morio Ueno, Daniel Gaston, Paul Rafuse, Lesya Shuba, Joseph Saunders, Marcelo Nicolela, George Chichua, Sergo Tabagari, Panayiota Founti, Kar Seng Sim, Wee Yang Meah, Hui Meng Soo, Xiao Yin Chen, Anthi Chatzikyriakidou, Christina Keskini, Theofanis Pappas, Eleftherios Anastasopoulos, Alexandros Lambropoulos, Evangelia S Panagiotou, Dimitrios G Mikropoulos, Ewa Kosior-Jarecka, Augustine Cheong, Yuanhan Li, Urszula Lukasik, Monisha E Nongpiur, Rahat Husain, Shamira A Perera, Lydia Álvarez, Montserrat García, Héctor González-Iglesias, Andrés F V Cueto, Luis F V Cueto, Federico Martinón-Torres, Antonio Salas, Çilingir Oguz, Nevbahar Tamcelik, Eray Atalay, Bilge Batu, Murat Irkec, Dilek Aktas, Burcu Kasim, Yury S Astakhov, Sergei Y Astakhov, Eugeny L Akopov, Andreas Giessl, Christian Mardin, Claus Hellerbrand, Jessica N Cooke Bailey, Robert P Igo Jr, Jonathan L Haines, Deepak P Edward, Steffen Heegaard, Sonia Davila, Patrick Tan, Jae H Kang, Louis R Pasquale, Friedrich E Kruse, André Reis, Trevor R Carmichael, Michael Hauser, Michele Ramsay, Georg Mossböck, Nilgun Yildirim, Kei Tashiro, Anastasios G P Konstas, Miguel Coca-Prados, Jia Nee Foo, Shigeru Kinoshita, Chie Sotozono, Toshiaki Kubota, Michael Dubina, Robert Ritch, Janey L Wiggs, Francesca Pasutto, Ursula Schlötzer-Schrehardt, Ying Swan Ho, Tin Aung, Wai Leong Tam, Chiea Chuen Khor (2021) Association of Rare CYP39A1 Variants With Exfoliation Syndrome Involving the Anterior Chamber of the Eye. JAMA 325(8): 753-764
  • Ser Yue Loo, Li Ping Toh †, William Haowei Xie †, Elina Pathak, Wilson Tan, Siming Ma, May Yin Lee, S. Shatishwaran, Joanna Zhen Zhen Yeo, Ju Yuan, Yin Ying Ho, Esther Kai Lay Peh, Magendran Muniandy, Federico Torta, Jack Chan, Tira J. Tan, Yirong Sim, Veronique Tan, Benita Tan, Preetha Madhukumar, Wei Sean Yong, Kong Wee Ong, Chow Yin Wong, Puay Hoon Tan, Yoon Sim Yap, Lih-Wen Deng, Rebecca Dent, Roger Foo, Markus R. Wenk, Soo Chin Lee, Ying Swan Ho, Elaine Hsuen Lim and Wai Leong Tam (2021) Fatty acid oxidation is a druggable gateway regulating cellular plasticity for driving metastasis in breast cancer. Science Advances 7(41): eabh2443.
  • Alison P. Lee, Yee Jiun Kok, Meiyappan Lakshmanan, Dawn Leong, Lu Zheng, Hsueh Lee Lim, Shuwen Chen, Shi Ya Mak, Kok Siong Ang, Neil Templeton, Taha Salim, Xiaona Wei, Eric Gifford, Andy Hee‐Meng Tan, Xuezhi Bi, Say Kong Ng, Dong‐Yup Lee, Wai Lam W. Ling and Ying Swan Ho (2021) Multi-omics profiling of a CHO cell culture system unravels the effect of culture pH on cell growth, antibody titer, and product quality. Biotechnology and Bioengineering 118(11): 4305-4316
  • Zhenxun Wang, Lian Yee Yip, Jia Hui Jane Lee, Zhengwei Wu, Hui Yi Chew, Pooi Kiat William Chong, Chin Chye Teo, Heather Yin-Kuan Ang, Kai Lay Esther Peh, Ju Yuan, Siming Ma, Li Shi Kimberly Choo, Nurhidayah Basri, Xia Jiang, Qiang Yu, Axel M. Hillmer, Wan Teck Lim, Tony Kiat Hon Lim, Angela Takano, Eng Huat Tan, Daniel Shao Weng Tan, Ying Swan Ho, Bing Lim and Wai Leong Tam (2019) Methionine is a metabolic dependency of tumor-initiating cells. Nature Medicine 25: 825-837.

Landmark Patents & IP

  • Method of treating a methionine-dependant cancer (2022)
  • Rapid analysis and identification of lipids from liquid chromatography-mass spectrometry (LC-MS) data (2018)

The Team

Dr Ho Ying Swan

Dr Ho Ying Swan

ho_ying_swan@bti.a-star.edu.sg
Senior Principal Scientist I

PhD in Chemical Engineering (2007), Imperial College, UK

Research Focus / Interest

  • Metabolomics/metabolite profiling of mammalian cell lines to further understanding of intracellular metabolic processes and their impact on recombinant protein production and quality
  • Application of metabolite profiling to identify candidate disease markers and to study aberrant metabolism under disease conditions
ho yin ying

Dr Ho Yin Ying

ho_yin_ying@bti.a-star.edu.sg
Senior Scientist II

PhD in Plant Biochemistry (2018), The University of Melbourne, Australia

Research Focus / Interest

  • Advancing analytical tools for metabolite identification
  • Targeted and non-targeted metabolomics
  • Characterize cell- and animal-based models for drug development
Annie Soh (updated)

Dr Annie Soh

annie_soh@bti.a-star.edu.sg
Scientist

PhD in Sustainable Earth (Interdisciplinary Graduate Program) (2020), Nanyang Technological University, Singapore

Research Focus / Interest

  • Characterisation of lipids and metabolites for drug development
  • The advancement of metabolomics in toxicological studies and resource recovery
Kang Yu Hui

Dr Kang Yu Hui

kang_yu_hui@bti.a-star.edu.sg
Scientist

PhD in Immunology (2019), Harvard University, USA

Research Focus / Interest

  • Application of metabolomics to the study of biological systems (e.g. the immune system)
  • Integrating metabolomics with other research techniques to improve metabolic studies

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