Overview
Background
Biography
Jeffrey Mak (PhD) is an organic chemist at the Institute for Molecular Bioscience. His publications cover a range of disciplines such as biological and medicinal chemistry, total synthesis, and physical organic chemistry. Dr Mak was selected as a Rising Star of Chemistry by the Australian Journal of Chemistry (2022).
Jeffrey Mak was awarded the Harriett Marks Bursary and a UQ University Medal before undertaking doctorate studies in natural product total synthesis with Prof. Craig Williams. This culminated in the first total synthesis of two caged diterpenes, (−)-neovibsanin G and (−)-14-epi-neovibsanin G. Next, he joined Prof. David Fairlie's group at the Institute for Molecular Bioscience. He is currently active in the fields of chemical biology and drug development. He is recognised for his development of ligands that modulate mucosal associated invariant T (MAIT) cells, which are a newly characterised subset of immune cells important in antibacterial defence (Accounts of Chemical Research, 2021). In 2014, he was part of an Australian team that discovered the identity of the ligands that activate MAIT cells, as published in Nature, playing a key role in the chemical synthesis and characterisation of the unstable and structurally unprecedented ligands (Nature Communications, 2017). He was selected as a CAS SciFinder Future Leader by the Chemical Abstract Service (a division of the American Chemical Society, 2017). In 2018, Dr Mak was chief investigator on a UQ Early Career Researcher Grant for developing new drug leads that target MAIT cells. Other recent awards include RSC Twitter Poster Conference (Chemical Biology) 1st Prize (2018), and a CASS Travel Award (2018).
Dr Mak has lectured in the undergraduate course Advanced Organic Chemistry (CHEM3001, 2017-2023). He has also served as a member of the UQ Cultural Inclusion Council, and as an ACS Wikipedia Fellow to systematically improve the chemistry and scientific content on Wikipedia (2018).
Student projects
Projects in medicinal chemistry, synthesis, and chemical biology are available (depending on lab space) for enthusiastic organic chemistry students at all levels (PhD, Masters, Honours, Undergraduate). These include the design and synthesis of:
- Stable analogues of immunostimulating bacterial ligands towards vaccines and anti-cancer immunotherapies
- Chemical biology tools for exploring MAIT cell activation
- Highly selective histone deacetylase (HDAC) inhibitors as new drug leads
Previous student publications:
- Mak JYW* et al. (2024) Potent Immunomodulators Developed from an Unstable Bacterial Metabolite of Vitamin B2 Biosynthesis. Angewandte Chemie, e202400632.
- Mak JYW et al. (2021) HDAC7 inhibition by phenacetyl and phenylbenzoyl hydroxamates. Journal of Medicinal Chemistry, 64 (4), 2186-2204.
- Awad W, Ler GJM et al. (2020) The molecular basis underpinning the potency and specificity of MAIT cell antigens. Nature Immunology, 21 (4), 400-411.
- Ler GJM, Xu W, Mak JYW, Liu L et al. (2019) Computer modelling and synthesis of deoxy and monohydroxy analogues of a ribitylaminouracil bacterial metabolite that potently activates human T cells. Chemistry – A European Journal, 25 (68), 15594-15608.
Availability
- Dr Jeffrey Mak is:
- Available for supervision
- Media expert
Fields of research
Qualifications
- Bachelor (Honours) of Science (Advanced), The University of Queensland
- Doctor of Philosophy, The University of Queensland
Research interests
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Mucosal associated invariant T cell (MAIT cell) ligands
MAIT cells play an important role in antibacterial immune defence. Unlike other T cells, MAIT cells are activated by small heterocyclic molecules. I am interested in using small molecule synthetic chemistry to develop new compounds as research tools for studying MAIT cells. This includes the development of compounds that activate MAIT cells as potential immunostimulants, components of vaccines, and immunotherapeutic agents. However, uncontrolled MAIT cell activation has also been linked to disease, so I am also interested in developing inhibitors of MAIT cell activation as potential anti-inflammatory agents for diseases such as ulcerative colitis and inflammatory bowel disease. These activities contribute to my overall goal of uncovering the physiological roles and harnessing the therapeutic potential of MAIT cells.
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Drug design and development against GPCR and enzyme targets
I am interested in developing potent and selective ligands against GPCR and enzyme targets. These are highly collaborative and multidisciplinary projects involving computer aided design, chemical synthesis, in vitro bioassay, and experimental pharmacology. The aim is to use collective expertise to develop drugs as potential treatments for inflammatory disease. For example, recently, we developed best-in-class drug-like inhibitors of class IIa histone deacetylases, which are emerging targets for cancer and inflammatory disease.
Research impacts
Research tools
Dr Mak played the key role in the synthesis of the ligands 5-OP-RU and its functionally similar and stable analogue as MAIT cell research reagents (1 patent). These are currently used in twenty labs worldwide and have enabled >15 papers in the MAIT cell field.
Selected talks
- ACS National Meeting and Exposition (Rising Stars in Biochemistry and Chemical Biology), New Orleans, USA, 2024
- RACI National Congress, Brisbane, 2022
- Invited: ARC Centre of Excellence in Advanced Molecular Imaging Legacy and Scientific Summit, Yarra Valley, Australia, 2021
- Invited: 8th Heron Conference on Reactive Intermediates and Unusual Molecules, Uluru, Australia, 2019
- Invited: Griffith Institute for Drug Discovery, Brisbane, May, 2019
- IUPAC International Conference on Organic Synthesis, Florence, Italy, 2018 (sponsored by CASS Travel Award)
- 254th ACS National Meeting and Exposition, Washington D.C., USA, 2017 (sponsored by CAS SciFinder Future Leaders)
Selected awards
Dr Mak has received >10 awards/honours since 2007, including:
- Australian Journal of Chemistry - Rising Star of Chemistry (2022)
- Jo Underhill IMB Art Award (2019)
- CASS Travel Award (2018)
- RSC Twitter Poster Conference (Chemical Biology) 1st Prize (2018)
- CAS SciFinder Future Leader (2017)
- RACI Centenary Congress Best Science Communication Prize (2017)
- Brisbane Biological and Organic Chemistry Symposium Best Talk (2011)
- UQ University Medal (2007)
Works
Search Professor Jeffrey Mak’s works on UQ eSpace
2024
Journal Article
Potent immunomodulators developed from an unstable bacterial metabolite of vitamin B2 biosynthesis
Mak, Jeffrey Y. W., Rivero, Ryan J. D., Hoang, Huy N., Lim, Xin Yi, Deng, Jieru, McWilliam, Hamish E. G., Villadangos, Jose A., McCluskey, James, Corbett, Alexandra J. and Fairlie, David P. (2024). Potent immunomodulators developed from an unstable bacterial metabolite of vitamin B2 biosynthesis. Angewandte Chemie (International Edition), 63 (31) e202400632, e202400632. doi: 10.1002/anie.202400632
Featured
2021
Journal Article
Chemical modulators of mucosal associated Invariant T cells
Mak, Jeffrey Y.W., Liu, Ligong and Fairlie, David P. (2021). Chemical modulators of mucosal associated Invariant T cells. Accounts of Chemical Research, 54 (17) acs.accounts.1c00359, 3462-3475. doi: 10.1021/acs.accounts.1c00359
Featured
2021
Journal Article
HDAC7 inhibition by phenacetyl and phenylbenzoyl hydroxamates
Mak, Jeffrey Y. W., Wu, Kai-Chen, Gupta, Praveer K., Barbero, Sheila, McLaughlin, Maddison G., Lucke, Andrew J., Tng, Jiahui, Lim, Junxian, Loh, Zhixuan, Sweet, Matthew J, Reid, Robert C., Liu, Ligong and Fairlie, David P. (2021). HDAC7 inhibition by phenacetyl and phenylbenzoyl hydroxamates. Journal of Medicinal Chemistry, 64 (4), 2186-2204. doi: 10.1021/acs.jmedchem.0c01967
Featured
2020
Journal Article
Endoplasmic reticulum chaperones stabilize ligand-receptive MR1 molecules for efficient presentation of metabolite antigens
McWilliam, Hamish E. G., Mak, Jeffrey Y. W., Awad, Wael, Zorkau, Matthew, Cruz-Gomez, Sebastian, Lim, Hui Jing, Yan, Yuting, Wormald, Sam, Dagley, Laura F., Eckle, Sidonia B. G., Corbett, Alexandra J., Liu, Haiyin, Li, Shihan, Reddiex, Scott J. J., Mintern, Justine D., Liu, Ligong, McCluskey, James, Rossjohn, Jamie, Fairlie, David P. and Villadangos, Jose A. (2020). Endoplasmic reticulum chaperones stabilize ligand-receptive MR1 molecules for efficient presentation of metabolite antigens. Proceedings of the National Academy of Sciences, 117 (40), 1-12. doi: 10.1073/pnas.2011260117
2017
Journal Article
Stabilizing short-lived Schiff base derivatives of 5-aminouracils that activate mucosal-associated invariant T cells
Mak, Jeffrey Y. W., Xu, Weijun, Reid, Robert C., Corbett, Alexandra J., Meehan, Bronwyn S., Wang, Huimeng, Chen, Zhenjun, Rossjohn, Jamie, McCluskey, James, Liu, Ligong and Fairlie, David P. (2017). Stabilizing short-lived Schiff base derivatives of 5-aminouracils that activate mucosal-associated invariant T cells. Nature Communications, 8 (1) 14599, 14599. doi: 10.1038/ncomms14599
Featured
2014
Journal Article
Natural Products with Anti-Bredt and Bridgehead Double Bonds
Mak, Jeffrey Y. W., Pouwer, Rebecca H. and Williams, Craig M. (2014). Natural Products with Anti-Bredt and Bridgehead Double Bonds. Angewandte Chemie International Edition, 53 (50), 13664-13688. doi: 10.1002/anie.201400932
2014
Journal Article
T-cell activation by transitory neo-antigens derived from distinct microbial pathways
Corbett, Alexandra J., Eckle, Sidonia B. G., Birkinshaw, Richard W., Liu, Ligong, Patel, Onisha, Mahony, Jennifer, Chen, Zhenjun, Reantragoon, Rangsima, Meehan, Bronwyn, Cao, Hanwei, Williamson, Nicholas A., Strugnell, Richard A., Van Sinderen, Douwe, Mak, Jeffrey Y. W., Fairlie, David P., Kjer-Nielsen, Lars, Rossjohn, Jamie and McClusky, James (2014). T-cell activation by transitory neo-antigens derived from distinct microbial pathways. Nature, 509 (7500), 361-365. doi: 10.1038/nature13160
Featured
2012
Journal Article
Enantioselective total synthesis of (-)-neovibsanin G and (-)-14-epi-neovibsanin G
Mak, Jeffrey Y.W. and Williams, Craig M. (2012). Enantioselective total synthesis of (-)-neovibsanin G and (-)-14-epi-neovibsanin G. Chemical Communications, 48 (2), 287-289. doi: 10.1039/c1cc15995j
2024
Journal Article
MAIT cell heterogeneity across paired human tissues reveals specialization of distinct regulatory and enhanced effector profiles
Kammann, Tobias, Cai, Curtis, Sekine, Takuya, Mouchtaridi, Elli, Boulouis, Caroline, Nilsén, Vera, Ballesteros, Olga Rivera, Müller, Thomas R., Gao, Yu, Raineri, Elisa J. M., Mily, Akhirunnesa, Adamo, Sarah, Constantz, Christian, Niessl, Julia, Weigel, Whitney, Kokkinou, Efthymia, Stamper, Christopher, Marchalot, Anne, Bassett, John, Ferreira, Sabrina, Rødahl, Inga, Wild, Nicole, Brownlie, Demi, Tibbitt, Chris, Mak, Jeffrey Y. W., Fairlie, David P., Leeansyah, Edwin, Michaelsson, Jakob, Marquardt, Nicole ... Sandberg, Johan K. (2024). MAIT cell heterogeneity across paired human tissues reveals specialization of distinct regulatory and enhanced effector profiles. Science Immunology, 9 (99) eadn2362, eadn2362. doi: 10.1126/sciimmunol.adn2362
2024
Journal Article
Varicella Zoster Virus disrupts MAIT cell polyfunctional effector responses
Purohit, Shivam K., Stern, Lauren, Corbett, Alexandra J., Mak, Jeffrey Y.W., Fairlie, David P., Slobedman, Barry and Abendroth, Allison (2024). Varicella Zoster Virus disrupts MAIT cell polyfunctional effector responses. PLoS Pathogens, 20 (8 August) e1012372, e1012372. doi: 10.1371/journal.ppat.1012372
2024
Journal Article
Potent Immunomodulators Developed from an Unstable Bacterial Metabolite of Vitamin B2 Biosynthesis
Mak, Jeffrey Y. W., Rivero, Ryan J. D., Hoang, Huy N., Lim, Xin Yi, Deng, Jieru, McWilliam, Hamish E. G., Villadangos, Jose A., McCluskey, James, Corbett, Alexandra J. and Fairlie, David P. (2024). Potent Immunomodulators Developed from an Unstable Bacterial Metabolite of Vitamin B2 Biosynthesis. Angewandte Chemie, 136 (31). doi: 10.1002/ange.202400632
2024
Journal Article
MAIT cell activation and recruitment in inflammation and tissue damage in acute appendicitis
Zheng, Yichao, Han, Fei, Wu, Zhengyu, Wang, Bingjie, Chen, Xingchi, Boulouis, Caroline, Jiang, Yuebin, Ho, Amanda, He, Dan, Sia, Wan Rong, Mak, Jeffrey Y. W., Fairlie, David P., Wang, Lin-Fa, Sandberg, Johan K., Lobie, Peter E., Ma, Shaohua and Leeansyah, Edwin (2024). MAIT cell activation and recruitment in inflammation and tissue damage in acute appendicitis. Science Advances, 10 (24) eadn6331, eadn6331. doi: 10.1126/sciadv.adn6331
2024
Journal Article
MAIT cell-MR1 reactivity is highly conserved across multiple divergent species
Edmans, Matthew D., Connelley, Timothy K., Morgan, Sophie, Pediongco, Troi J., Jayaraman, Siddharth, Juno, Jennifer A., Meehan, Bronwyn S., Dewar, Phoebe M., Maze, Emmanuel A., Roos, Eduard O., Paudyal, Basu, Mak, Jeffrey YW., Liu, Ligong, Fairlie, David P., Wang, Huimeng, Corbett, Alexandra J., McCluskey, James, Benedictus, Lindert, Tchilian, Elma, Klenerman, Paul and Eckle, Sidonia BG. (2024). MAIT cell-MR1 reactivity is highly conserved across multiple divergent species. Journal of Biological Chemistry, 300 (6) 107338, 107338. doi: 10.1016/j.jbc.2024.107338
2024
Journal Article
Mouse mucosal-associated invariant T cell receptor recognition of MR1 presenting the vitamin B metabolite, 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil
Ciacchi, Lisa, Mak, Jeffrey Y.W., Le, Jeremy P., Fairlie, David P., McCluskey, James, Corbett, Alexandra J., Rossjohn, Jamie and Awad, Wael (2024). Mouse mucosal-associated invariant T cell receptor recognition of MR1 presenting the vitamin B metabolite, 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil. Journal of Biological Chemistry, 300 (5) 107229, 107229. doi: 10.1016/j.jbc.2024.107229
2024
Journal Article
Sulfated bile acid is a host-derived ligand for MAIT cells
Ito, Emi, Inuki, Shinsuke, Izumi, Yoshihiro, Takahashi, Masatomo, Dambayashi, Yuki, Ciacchi, Lisa, Awad, Wael, Takeyama, Ami, Shibata, Kensuke, Mori, Shotaro, Mak, Jeffrey Y. W., Fairlie, David P., Bamba, Takeshi, Ishikawa, Eri, Nagae, Masamichi, Rossjohn, Jamie and Yamasaki, Sho (2024). Sulfated bile acid is a host-derived ligand for MAIT cells. Science Immunology, 9 (91) ARTN eade6924, eade6924. doi: 10.1126/sciimmunol.ade6924
2023
Journal Article
Dynamic MAIT cell recovery after severe COVID-19 is transient with signs of heterogeneous functional anomalies
Kammann, Tobias, Gorin, Jean-Baptiste, Parrot, Tiphaine, Gao, Yu, Ponzetta, Andrea, Emgård, Johanna, Maleki, Kimia T., Sekine, Takuya, Rivera-Ballesteros, Olga, Gredmark-Russ, Sara, Rooyackers, Olav, Skagerberg, Magdalena, Eriksson, Lars I., Norrby-Teglund, Anna, Mak, Jeffrey Y. W., Fairlie, David P., Björkström, Niklas K., Klingström, Jonas, Ljunggren, Hans-Gustaf, Aleman, Soo, Buggert, Marcus, Strålin, Kristoffer, Sandberg, Johan K. and Karolinska COVID-19 Study Group (2023). Dynamic MAIT cell recovery after severe COVID-19 is transient with signs of heterogeneous functional anomalies. The Journal of Immunology, 212 (3), 389-396. doi: 10.4049/jimmunol.2300639
2023
Journal Article
Synthetic 5-amino-6-D-ribitylaminouracil paired with inflammatory stimuli facilitates MAIT cell expansion in vivo
Nelson, Adam G., Wang, Huimeng, Dewar, Phoebe M., Eddy, Eleanor M., Li, Songyi, Lim, Xin Yi, Patton, Timothy, Zhou, Yuchen, Pediongco, Troi J., Meehan, Lucy J., Meehan, Bronwyn S., Mak, Jeffrey Y. W., Fairlie, David P., Stent, Andrew W., Kjer-Nielsen, Lars, McCluskey, James, Eckle, Sidonia B. G., Corbett, Alexandra J., Souter, Michael N. T. and Chen, Zhenjun (2023). Synthetic 5-amino-6-D-ribitylaminouracil paired with inflammatory stimuli facilitates MAIT cell expansion in vivo. Frontiers in Immunology, 14 1109759, 1-15. doi: 10.3389/fimmu.2023.1109759
2023
Journal Article
Histone deacetylase 7: a signalling hub controlling development, inflammation, metabolism and disease
Wang, Yizhuo, Abrol, Rishika, Mak, Jeffrey Y. W., Das Gupta, Kaustav, Ramnath, Divya, Karunakaran, Denuja, Fairlie, David P. and Sweet, Matthew J. (2023). Histone deacetylase 7: a signalling hub controlling development, inflammation, metabolism and disease. The FEBS Journal, 290 (11), 2805-2832. doi: 10.1111/febs.16437
2022
Journal Article
Quantitative affinity measurement of small molecule ligand binding to Major Histocompatibility Complex class-I related protein 1 MR1
Wang, Carl J.H., Awad, Wael, Liu, Ligong, Mak, Jeffrey Y.W., Veerapen, Natacha, Illing, Patricia T., Purcell, Anthony W., Eckle, Sidonia B.G., McCluskey, James, Besra, Gurdyal S., Fairlie, David P., Rossjohn, Jamie and Le Nours, Jérôme (2022). Quantitative affinity measurement of small molecule ligand binding to Major Histocompatibility Complex class-I related protein 1 MR1. Journal of Biological Chemistry, 298 (12) 102714, 1-12. doi: 10.1016/j.jbc.2022.102714
2022
Journal Article
A specialized tyrosine-based endocytosis signal in MR1 controls antigen presentation to MAIT cells
Lim, Hui Jing, Wubben, Jacinta M., Garcia, Cristian Pinero, Cruz-Gomez, Sebastian, Deng, Jieru, Mak, Jeffrey Y.W., Hachani, Abderrahman, Anderson, Regan J., Painter, Gavin F., Goyette, Jesse, Amarasinghe, Shanika L., Ritchie, Matthew E., Roquilly, Antoine, Fairlie, David P., Gaus, Katharina, Rossjohn, Jamie, Villadangos, Jose A. and McWilliam, Hamish E.G. (2022). A specialized tyrosine-based endocytosis signal in MR1 controls antigen presentation to MAIT cells. Journal of Cell Biology, 221 (12) e202110125. doi: 10.1083/jcb.202110125
Funding
Past funding
Supervision
Availability
- Dr Jeffrey Mak is:
- Available for supervision
Before you email them, read our advice on how to contact a supervisor.
Supervision history
Current supervision
-
Doctor Philosophy
Design and synthesis of novel Major histocompatibility complex class I-Related protein ligands
Principal Advisor
Other advisors: Professor David Fairlie
-
Doctor Philosophy
Discovering novel anticancer drugs
Associate Advisor
Other advisors: Dr Tim Hill, Professor David Fairlie
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Doctor Philosophy
Novel activators and inhibitors of innate immune cells
Associate Advisor
Other advisors: Professor David Fairlie
-
Doctor Philosophy
Novel chemical approaches to drugs that selectively target immune cells
Associate Advisor
Other advisors: Professor David Fairlie
-
Doctor Philosophy
New strategies in heterocyclic chemistry for drug discovery
Associate Advisor
Other advisors: Professor David Fairlie
Completed supervision
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2020
Master Philosophy
Structure-function relationships of a ribityl uracil T-cell antigen
Associate Advisor
Other advisors: Professor David Fairlie
Media
Enquiries
Contact Dr Jeffrey Mak directly for media enquiries about:
- chemical bonds
- chemicals
- chemistry
- compounds
- drug design
- drug discovery
- drugs
- medicinal chemistry
- natural products
- organic chemistry
- reactions
- synthetic chemistry
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