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Dr Jeffrey Mak
Dr

Jeffrey Mak

Email: 
Phone: 
+61 7 334 62988

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:

  1. Stable analogues of immunostimulating bacterial ligands towards vaccines and anti-cancer immunotherapies
  2. Chemical biology tools for exploring MAIT cell activation
  3. Highly selective histone deacetylase (HDAC) inhibitors as new drug leads

Previous student publications:

  1. Mak JYW* et al. (2024) Potent Immunomodulators Developed from an Unstable Bacterial Metabolite of Vitamin B2 Biosynthesis. Angewandte Chemie, e202400632.
  2. Mak JYW et al. (2021) HDAC7 inhibition by phenacetyl and phenylbenzoyl hydroxamates. Journal of Medicinal Chemistry, 64 (4), 2186-2204.
  3. 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.
  4. 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

Qualifications

  • Bachelor (Honours) of Science (Advanced), The University of Queensland
  • Doctor of Philosophy, The University of Queensland

Research interests

  • 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.

  • 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:

Works

Search Professor Jeffrey Mak’s works on UQ eSpace

64 works between 2009 and 2024

1 - 20 of 64 works

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

Potent immunomodulators developed from an unstable bacterial metabolite of vitamin B2 biosynthesis

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

Chemical modulators of mucosal associated Invariant T cells

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

HDAC7 inhibition by phenacetyl and phenylbenzoyl hydroxamates

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

Endoplasmic reticulum chaperones stabilize ligand-receptive MR1 molecules for efficient presentation of metabolite antigens

Featured

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

Stabilizing short-lived Schiff base derivatives of 5-aminouracils that activate mucosal-associated invariant T cells

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

Natural Products with Anti-Bredt and Bridgehead Double Bonds

Featured

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

T-cell activation by transitory neo-antigens derived from distinct microbial pathways

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

Enantioselective total synthesis of (-)-neovibsanin G and (-)-14-epi-neovibsanin G

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

Varicella Zoster Virus disrupts MAIT cell polyfunctional effector responses

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

Potent Immunomodulators Developed from an Unstable Bacterial Metabolite of Vitamin B2 Biosynthesis

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

MAIT cell activation and recruitment in inflammation and tissue damage in acute appendicitis

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

MAIT cell-MR1 reactivity is highly conserved across multiple divergent species

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

Mouse mucosal-associated invariant T cell receptor recognition of MR1 presenting the vitamin B metabolite, 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil

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

Sulfated bile acid is a host-derived ligand for MAIT cells

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

Dynamic MAIT cell recovery after severe COVID-19 is transient with signs of heterogeneous functional anomalies

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

Synthetic 5-amino-6-D-ribitylaminouracil paired with inflammatory stimuli facilitates MAIT cell expansion in vivo

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

Histone deacetylase 7: a signalling hub controlling development, inflammation, metabolism and disease

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

Quantitative affinity measurement of small molecule ligand binding to Major Histocompatibility Complex class-I related protein 1 MR1

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

A specialized tyrosine-based endocytosis signal in MR1 controls antigen presentation to MAIT cells

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

CD8 coreceptor engagement of MR1 enhances antigen responsiveness by human MAIT and other MR1-reactive T cells

Funding

Past funding

  • 2018
    Developing a drug lead to target a new and abundant immune cell
    UQ Early Career Researcher
    Open grant
  • 2014
    Continuous-Flow Hydrogenation Reactor (H-Cube Pro)
    UQ Major Equipment and Infrastructure
    Open grant

Supervision

Availability

Dr Jeffrey Mak is:
Available for supervision

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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

    Novel chemical approaches to drugs that selectively target immune cells

    Associate Advisor

    Other advisors: Professor David Fairlie

  • Doctor Philosophy

    Novel activators and inhibitors of innate 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

  • Doctor Philosophy

    Discovering novel anticancer drugs

    Associate Advisor

    Other advisors: Dr Tim Hill, Professor David Fairlie

Completed supervision

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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