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
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
2022
Journal Article
CD8 coreceptor engagement of MR1 enhances antigen responsiveness by human MAIT and other MR1-reactive T cells
Souter, Michael N.T., Awad, Wael, Li, Shihan, Pediongco, Troi J., Meehan, Bronwyn S., Meehan, Lucy J., Tian, Zehua, Zhao, Zhe, Wang, Huimeng, Nelson, Adam, Le Nours, Jérôme, Khandokar, Yogesh, Praveena, T., Wubben, Jacinta, Lin, Jie, Sullivan, Lucy C., Lovrecz, George O., Mak, Jeffrey Y.W., Liu, Ligong, Kostenko, Lyudmila, Kedzierska, Katherine, Corbett, Alexandra J., Fairlie, David P., Brooks, Andrew G., Gherardin, Nicholas A., Uldrich, Adam P., Chen, Zhenjun, Rossjohn, Jamie, Godfrey, Dale I. ... Eckle, Sidonia B.G. (2022). CD8 coreceptor engagement of MR1 enhances antigen responsiveness by human MAIT and other MR1-reactive T cells. Journal of Experimental Medicine, 219 (9) e20210828, 1-30. doi: 10.1084/jem.20210828
2022
Journal Article
Tuning electrostatic and hydrophobic surfaces of aromatic rings to enhance membrane association and cell uptake of peptides
de Araujo, Aline Dantes, Hoang, Huy N., Lim, Junxian, Mak, Jeffrey and Fairlie, David P. (2022). Tuning electrostatic and hydrophobic surfaces of aromatic rings to enhance membrane association and cell uptake of peptides. Angewandte Chemie International Edition, 61 (29) e202203995, e202203995. doi: 10.1002/anie.202203995
2022
Journal Article
Tuning Electrostatic and Hydrophobic Surfaces of Aromatic Rings to Enhance Membrane Association and Cell Uptake of Peptides
de Araujo, Aline D., Hoang, Huy N., Lim, Junxian, Mak, Jeffrey Y. W. and Fairlie, David P. (2022). Tuning Electrostatic and Hydrophobic Surfaces of Aromatic Rings to Enhance Membrane Association and Cell Uptake of Peptides. Angewandte Chemie, 134 (29). doi: 10.1002/ange.202203995
2022
Journal Article
The balance of IL ‐12 and IL ‐23 determines the bias of MAIT1 versus MAIT17 responses during bacterial infection
Wang, Huimeng, Nelson, Adam G., Wang, Bingjie, Zhao, Zhe, Lim, Xin Yi, Shi, Mai, Meehan, Lucy J., Jia, Xiaoxiao, Kedzierska, Katherine, Meehan, Bronwyn S., Eckle, Sidonia B. G., Souter, Michael N. T., Pediongco, Troi J., Mak, Jeffrey Y. W., Fairlie, David P., McCluskey, James, Wang, Zhongfang, Corbett, Alexandra J. and Chen, Zhenjun (2022). The balance of IL ‐12 and IL ‐23 determines the bias of MAIT1 versus MAIT17 responses during bacterial infection. Immunology & Cell Biology, 100 (7), 547-561. doi: 10.1111/imcb.12556
2022
Journal Article
Differential location of NKT and MAIT cells within lymphoid tissue
Johnson, Darryl N., Ruan, Zheng, Petley, Emma V., Devi, Sapna, Holz, Lauren E., Uldrich, Adam P., Mak, Jeffrey Y. W., Hor, Jyh Liang, Mueller, Scott N., McCluskey, James, Fairlie, David P., Darcy, Phillip K., Beavis, Paul A., Heath, William R. and Godfrey, Dale I. (2022). Differential location of NKT and MAIT cells within lymphoid tissue. Scientific Reports, 12 (1) 4034, 4034. doi: 10.1038/s41598-022-07704-4
2022
Journal Article
Inhibition of the master regulator of Listeria monocytogenes virulence enables bacterial clearance from spacious replication vacuoles in infected macrophages
Tran, Thao Thanh, Mathmann, Carmen D., Gatica-Andrades, Marcela, Rollo, Rachel F., Oelker, Melanie, Ljungberg, Johanna K., Nguyen, Tam T. K., Zamoshnikova, Alina, Kummari, Lalith K., Wyer, Orry J. K., Irvine, Katharine M., Melo-Bolívar, Javier, Gross, Annette, Brown, Darren, Mak, Jeffrey Y. W., Fairlie, David P., Hansford, Karl A., Cooper, Matthew A., Giri, Rabina, Schreiber, Veronika, Joseph, Shannon R., Simpson, Fiona, Barnett, Timothy C., Johansson, Jörgen, Dankers, Wendy, Harris, James, Wells, Timothy J., Kapetanovic, Ronan, Sweet, Matthew J. ... Blumenthal, Antje (2022). Inhibition of the master regulator of Listeria monocytogenes virulence enables bacterial clearance from spacious replication vacuoles in infected macrophages. PLoS Pathogens, 18 (1) e1010166, e1010166. doi: 10.1371/journal.ppat.1010166
2021
Journal Article
Human MAIT cells respond to and suppress HIV-1
Phetsouphanh, Chansavath, Phalora, Prabhjeet, Hackstein, Carl-Philipp, Thornhill, John, Munier, Mee Ling, Meyerowitz, Jodi, Murray, Lyle, VanVuuren, Cloete, Goedhals, Dominique, Drexhage, Linnea, Moore, Rebecca, Sattentau, Quentin J, Mak, Jeffrey YW, Fairlie, David P, Fidler, Sarah, Kelleher, Anthony, Frater, John and Klenerman, Paul (2021). Human MAIT cells respond to and suppress HIV-1. eLife, 10 e50324. doi: 10.7554/elife.50324
2021
Journal Article
MAIT cells regulate NK cell-mediated tumor immunity
Petley, Emma V., Koay, Hui-Fern, Henderson, Melissa A., Sek, Kevin, Todd, Kirsten L., Keam, Simon P., Lai, Junyun, House, Imran G., Li, Jasmine, Zethoven, Magnus, Chen, Amanda X. Y., Oliver, Amanda J., Michie, Jessica, Freeman, Andrew J., Giuffrida, Lauren, Chan, Jack D., Pizzolla, Angela, Mak, Jeffrey Y. W., McCulloch, Timothy R., Souza-Fonseca-Guimaraes, Fernando, Kearney, Conor J., Millen, Rosemary, Ramsay, Robert G., Huntington, Nicholas D., McCluskey, James, Oliaro, Jane, Fairlie, David P., Neeson, Paul J., Godfrey, Dale I. ... Darcy, Phillip K. (2021). MAIT cells regulate NK cell-mediated tumor immunity. Nature Communications, 12 (1) 4746, 1-15. doi: 10.1038/s41467-021-25009-4
2021
Journal Article
Francisella tularensis induces Th1 like MAIT cells conferring protection against systemic and local infection
Zhao, Zhe, Wang, Huimeng, Shi, Mai, Zhu, Tianyuan, Pediongco, Troi, Lim, Xin Yi, Meehan, Bronwyn S., Nelson, Adam G., Fairlie, David P., Mak, Jeffrey Y. W., Eckle, Sidonia B. G., de Lima Moreira, Marcela, Tumpach, Carolin, Bramhall, Michael, Williams, Cameron G., Lee, Hyun Jae, Haque, Ashraful, Evrard, Maximilien, Rossjohn, Jamie, McCluskey, James, Corbett, Alexandra J. and Chen, Zhenjun (2021). Francisella tularensis induces Th1 like MAIT cells conferring protection against systemic and local infection. Nature Communications, 12 (1) 4355, 1-15. doi: 10.1038/s41467-021-24570-2
2021
Journal Article
Identification and phenotype of MAIT cells in cattle and their response to bacterial infections
Edmans, Matthew D., Connelley, Timothy K., Jayaraman, Siddharth, Vrettou, Christina, Vordermeier, Martin, Mak, Jeffrey Y. W., Liu, Ligong, Fairlie, David P., Maze, Emmanuel Atangana, Chrun, Tiphany, Klenerman, Paul, Eckle, Sidonia B. G., Tchilian, Elma and Benedictus, Lindert (2021). Identification and phenotype of MAIT cells in cattle and their response to bacterial infections. Frontiers in Immunology, 12 627173, 627173. doi: 10.3389/fimmu.2021.627173
2021
Journal Article
Mucosal-associated invariant t cell effector function is an intrinsic cell property that can be augmented by the metabolic cofactor α-ketoglutarate
Howson, Lauren J., Li, Jasmine, von Borstel, Anouk, Barugahare, Adele, Mak, Jeffrey Y. W., Fairlie, David P., McCluskey, James, Turner, Stephen J., Davey, Martin S. and Rossjohn, Jamie (2021). Mucosal-associated invariant t cell effector function is an intrinsic cell property that can be augmented by the metabolic cofactor α-ketoglutarate. The Journal of Immunology, 206 (7) ji2001048, 1425-1435. doi: 10.4049/jimmunol.2001048
2021
Journal Article
Determination of sample concentrations by PULCON NMR spectroscopy
Mak, Jeffrey Y. W. (2021). Determination of sample concentrations by PULCON NMR spectroscopy. Australian Journal of Chemistry, 75 (2), 160-164. doi: 10.1071/ch21149
2020
Journal Article
MR1-restricted T cells with MAIT-like characteristics are functionally conserved in the Pteropid Bat Pteropus alecto
Leeansyah, Edwin, Hey, Ying Ying, Sia, Wan Rong, Ng, Justin Han Jia, Gulam, Muhammad Yaaseen, Boulouis, Caroline, Zhu, Feng, Ahn, Matae, Mak, Jeffrey Y.W., Fairlie, David P., Kwa, Andrea Lay Hoon, Sandberg, Johan K. and Wang, Lin-Fa (2020). MR1-restricted T cells with MAIT-like characteristics are functionally conserved in the Pteropid Bat Pteropus alecto. iScience, 23 (12) 101876, 101876. doi: 10.1016/j.isci.2020.101876
2020
Journal Article
Artificially induced MAIT cells inhibit M. bovis BCG but not M. tuberculosis during in vivo pulmonary infection
Yu, Huifeng, Yang, Amy, Derrick, Steven, Mak, Jeffrey Y. W., Liu, Ligong, Fairlie, David P. and Cowley, Siobhan (2020). Artificially induced MAIT cells inhibit M. bovis BCG but not M. tuberculosis during in vivo pulmonary infection. Scientific Reports, 10 (1) 13579, 13579. doi: 10.1038/s41598-020-70615-9
2020
Journal Article
CXCL16 stimulates antigen-induced MAIT cell accumulation but trafficking during lung infection is CXCR6-independent
Yu, Huifeng, Yang, Amy, Liu, Ligong, Mak, Jeffrey Y. W., Fairlie, David P. and Cowley, Siobhan (2020). CXCL16 stimulates antigen-induced MAIT cell accumulation but trafficking during lung infection is CXCR6-independent. Frontiers in Immunology, 11 1773, 1773. doi: 10.3389/fimmu.2020.01773
2020
Journal Article
Absence of mucosal-associated invariant T cells in a person with a homozygous point mutation in MR1
Howson, Lauren J., Awad, Wael, von Borstel, Anouk, Lim, Hui Jing, McWilliam, Hamish E. G., Sandoval-Romero, Maria L., Majumdar, Shamik, Hamzeh, Abdul Rezzak, Andrews, Thomas D., McDermott, David H., Murphy, Philip M., Le Nours, Jérôme, Mak, Jeffrey Y. W., Liu, Ligong, Fairlie, David P., McCluskey, James, Villadangos, Jose A., Cook, Matthew C., Turner, Stephen J., Davey, Martin S., Ojaimi, Samar and Rossjohn, Jamie (2020). Absence of mucosal-associated invariant T cells in a person with a homozygous point mutation in MR1. Science Immunology, 5 (49) 9492, eabc9492. doi: 10.1126/sciimmunol.abc9492
2020
Journal Article
Human MAIT cell cytolytic effector proteins synergize to overcome carbapenem resistance in Escherichia coli
Boulouis, Caroline, Sia, Wan Rong, Gulam, Muhammad Yaaseen, Teo, Jocelyn Qi Min, Png, Yi Tian, Phan, Thanh Kha, Mak, Jeffrey Y. W., Fairlie, David P., Poon, Ivan K. H., Koh, Tse Hsien, Bergman, Peter, Lim, Chwee Ming, Wang, Lin-Fa, Kwa, Andrea Lay Hoon, Sandberg, Johan K. and Leeansyah, Edwin (2020). Human MAIT cell cytolytic effector proteins synergize to overcome carbapenem resistance in Escherichia coli. PLoS Biology, 18 (6) e3000644, e3000644. doi: 10.1371/journal.pbio.3000644
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
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Doctor Philosophy
Design and synthesis of novel Major histocompatibility complex class I-Related protein ligands
Principal Advisor
Other advisors: Professor David Fairlie
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Doctor Philosophy
Novel chemical approaches to drugs that selectively target immune cells
Associate Advisor
Other advisors: Professor David Fairlie
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Doctor Philosophy
Novel activators and inhibitors of innate immune cells
Associate Advisor
Other advisors: Professor David Fairlie
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Doctor Philosophy
Towards Selective Inhibitors and PROTACs of HDAC7
Associate Advisor
Other advisors: Professor David Fairlie
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Doctor Philosophy
New strategies in heterocyclic chemistry for drug discovery
Associate Advisor
Other advisors: Professor David Fairlie
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Doctor Philosophy
Discovering novel anticancer drugs
Associate Advisor
Other advisors: Dr Tim Hill, 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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