Chris SHAM

Affiliations

Associate Professor
Infectious Diseases Translational Research Programme and Department of Microbiology and Immunology

Biography

Lok-To (Chris) Sham is an Associate Professor in the Department of Microbiology and Immunology at the National University of Singapore (NUS). Chris has led a multidisciplinary program investigating the synthesis of capsular polysaccharides (CPS) and how it coordinates with other cell envelope layers. His team has developed methods for genetic glycoengineering and systems biology. Chris’s accomplishments have been recognized with the National Research Foundation Fellowship (Class of 2019), the 2024 Rising Star Award in Biological, Medicinal, and Pharmaceutical Chemistry from the American Chemical Society, the 2025 Research Excellence Award and the 2024 Graduate Mentor of the Year Award from the Yong Loo Lin School of Medicine, NUS. He also serves as Vice President of the Singapore Society of Microbiology and Biotechnology.

Professional Appointments

2025- Associate Professor with tenure, Department of Microbiology and Immunology, National University of Singapore
2023- Executive Board Member, Asian Federation of Biotechnology
2020- Vice President, Singapore Society of Microbiology and Biotechnology
2024- NUSMedSci Alliance Council Member, National University of Singapore
2024-2025 Research Director, Infectious Diseases Translational Research Programme, National University of Singapore
2017-2025 Assistant Professor, Department of Microbiology and Immunology, National University of Singapore
2022-2024 Deputy Research Director, Infectious Diseases Translational Research Programme, National University of Singapore
2019-2020 Visiting Assistant Professor, Department of Microbiology, Harvard Medical School
2012-2017 Postdoctoral fellow, Department of Microbiology and Immunobiology, Harvard Medical School

Education

2012 Ph.D. in Microbiology, Indiana University Bloomington
2006 M. Phil. in Biology, the Chinese University of Hong Kong
2004 B.Sc. in Molecular Biotechnology, the Chinese University of Hong Kong
2004 BBA minor in Integrated BBA program, the Chinese University of Hong Kong

Research Interest

Our research program explores the molecular mechanisms that underpin capsule synthesis and bacterial virulence. We want to understand how cell-surface glycans shape pathogenicity and immunogenicity. Integrating systems biology, we also dissect genetic pathways to identify vulnerabilities that may guide the development of novel drug screening strategies. My lab aims to address fundamental questions in cell biology while translating our findings to prevent and cure infectious diseases.

Current Research Projects

1. Defining Specificity of Capsule Enzymes
The specificity of capsule enzymes governs what is placed on the protective capsule in pneumococcus. We pioneered massively parallel approaches to test whether glycosyltransferases and ‘flippases’ are interchangeable. Our work elucidated the rules underlying the selectivity of each enzyme, helping us identify variants that relax or impose specificity. This knowledge facilitates the development of enabling technologies for engineering glycans. Using this platform, we produced a few medically relevant mammalian glycans, such as blood group antigens, the Galili antigen, and Lewis antigens.

2. Coordinating Capsule and Cell Wall Assembly
A delicate balance exists between capsule and cell wall synthesis to ensure survival inside the host. We show that the capsule synthesis machinery integrates into the bacterial cell division complex. The capsule enzymes arrive at the division ring sequentially, starting by recruiting the tyrosine kinase system, CpsCD, to the septum. If the recruitment sequence fails, the protective capsule will no longer cover the septum, making the cell susceptible to complement. Ongoing work is to study how capsule synthesis synchronizes with other cell envelope layers.

3. Linking Capsule Structure to Function
Our lab examines how variations in CPS structure affect the interaction between pneumococci and host cells. We explore the role of specific glycan structures in adhesion to human respiratory cultures, shedding light on how these molecular patterns influence immune evasion and colonization. These studies have significant implications for developing vaccines and therapies to better prevent pneumococcal infections.

4. Reinventing Systems Biology
We develop high-throughput approaches to mining genetic interactions to elucidate gene functions. An example is Dual Tn-seq, which combines the strength of randomly barcoded transposon sequencing (RB Tn-seq) with the widely used Cre-lox system. The work captured genetic interactions from roughly 68% of double mutants that could theoretically be made. This massive dataset guides us to learn new biology from presumably well-studied pathways.

Selected Publications

1. J.J. Zik, M. N. Price, A. P. Arkin, A. M. Deutschbauer, and L.-T. Sham, Dual transposon sequencing profiles the genetic interaction landscape in bacteria. Science (IF: 44.7). 389, eadt7685 (2025).
2. C. K.-R. Wong, Y.-Y. Chun, T. Su, and L.-T. Sham. Leveraging the capsular polysaccharide synthesis pathway in Streptococcus pneumoniae as a genetic glycoengineering platform. ACS Bio & Med Chem Au (IF: 4.3). 5, 342-9 (2025). Invited review article in the “2024 Rising Stars in Biological, Medicinal, and Pharmaceutical Chemistry” issue.
3. W. Z. Chua, R. L. E. Wong, Y.-Y. Chun, N. C. S. Ng, T. Su, M. Maiwald, K. L. Chew, R. T. P. Lin, A. M. Hockenberry, M. Luo, L.-T. Sham, Massively parallel barcode sequencing revealed the interchangeability of capsule transporters in Streptococcus pneumoniae. Science Advances (IF: 13.6). 11, eadr0162 (2025).
4. L. Yu, X. Xu, W.-Z. Chua, H. Feng, Z. Ser, K. Shao, J. Shi, Y. Wang, Z. Li, R. M. Sobota, L.-T. Sham†, M. Luo†, Structural basis of peptide secretion for quorum sensing by ComA. Nature Communications (IF: 16.6). 14, 7178 (2023). †co-corresponding authors.
5. X. Xu, J. Li, W.-Z. Chua, M. A. Pages, J. Shi, J. A. Hermoso†, T. Bernhardt†, L.-T. Sham†, M. Luo†, Mechanistic insights into the regulation of cell wall hydrolysis by FtsEX and EnvC at the bacterial division site. Proceedings of the National Academy of Sciences of the United States of America (IF: 11.1). 120, e2301897120 (2023). †co-corresponding authors.
6. T. Su, W.-Z. Chua, Y. Liu, J. Fan, S.-Y. Tan, D.-W. Yang, L.-T. Sham, Rewiring the pneumococcal capsule pathway for investigating glycosyltransferase specificity and genetic glycoengineering. Science Advances (IF: 13.6). 9, eadi8157 (2023).
7. T. R. Nakamoto, S. Bamyaci, K. Blomqvist, S. Normark, B. Henriques-Normark, L.-T. Sham, The divisome but not the elongasome organizes capsule synthesis in Streptococcus pneumoniae. Nature Communications (IF: 16.6). 14, 3170 (2023).
8. Y.-Y. Chun, K. S. Tan, L. Yu, M. Pang, M. H. M. Wong, R. Nakamoto, W.-Z. Chua, A. Huee-Ping Wong, Z. Z. R. Lew, H. H. Ong, V. T. Chow, T. Tran, D. Yun Wang, L.-T. Sham, Influence of glycan structure on the colonization of Streptococcus pneumoniae on human respiratory epithelial cells. Proceedings of the National Academy of Sciences of the United States of America (IF: 11.1). 120, e2213584120 (2023).
9. T. Su, R. Nakamoto, Y.-Y. Chun, W.-Z. Chua, J.-H. Chen, J. J. Zik, L.-T. Sham, Decoding capsule synthesis in Streptococcus pneumoniae. FEMS Microbiology Reviews (IF: 11.3). 45, fuaa067 (2021). Review article.
10. R. Nakamoto, J. M. C. Kwan, J. F. L. Chin, H. T. Ong, J. Flores-Kim, C. Midonet, M. S. VanNieuwenhze, X. L. Guan, L.-T. Sham, The bacterial tyrosine kinase system CpsBCD governs the length of capsule polymers. Proceedings of the National Academy of Sciences of the United States of America (IF: 11.1). 118, e2103377118 (2021).

* Corresponding author; # Co-first author