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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

21 - 40 of 64 works

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

Tuning electrostatic and hydrophobic surfaces of aromatic rings to enhance membrane association and cell uptake of peptides

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

Tuning Electrostatic and Hydrophobic Surfaces of Aromatic Rings to Enhance Membrane Association and Cell Uptake of Peptides

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

The balance of IL ‐12 and IL ‐23 determines the bias of MAIT1 versus MAIT17 responses during bacterial infection

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

Differential location of NKT and MAIT cells within lymphoid tissue

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

Inhibition of the master regulator of Listeria monocytogenes virulence enables bacterial clearance from spacious replication vacuoles in infected macrophages

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

Human MAIT cells respond to and suppress HIV-1

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

MAIT cells regulate NK cell-mediated tumor immunity

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

Francisella tularensis induces Th1 like MAIT cells conferring protection against systemic and local infection

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

Identification and phenotype of MAIT cells in cattle and their response to bacterial infections

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

Mucosal-associated invariant t cell effector function is an intrinsic cell property that can be augmented by the metabolic cofactor α-ketoglutarate

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

Determination of sample concentrations by PULCON NMR spectroscopy

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

MR1-restricted T cells with MAIT-like characteristics are functionally conserved in the Pteropid Bat Pteropus alecto

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

Artificially induced MAIT cells inhibit M. bovis BCG but not M. tuberculosis during in vivo pulmonary infection

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

CXCL16 stimulates antigen-induced MAIT cell accumulation but trafficking during lung infection is CXCR6-independent

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

Absence of mucosal-associated invariant T cells in a person with a homozygous point mutation in MR1

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

Human MAIT cell cytolytic effector proteins synergize to overcome carbapenem resistance in Escherichia coli

2020

Journal Article

A divergent transcriptional landscape underpins the development and functional branching of MAIT cells

Koay, Hui Fern, Su, Shian, Amann-Zalcenstein, Daniela, Daley, Stephen R, Comerford, Iain, Whyte, Carly E, Konstantinov, Igor E, d’Udekem, Yves, Baldwin, Tracey, Hickey, Peter F, Berzins, Stuart P, Mak, Jeffrey Y.W., Kallies, Axel, Chen, Zhenjun, Nussing, Simone, Kedzierska, Katherine, Mackay, Laura K, McColl, Shaun R, Deenick, Elissa K, Fairlie, David P, McCluskey, James, Goodnow, Christopher C, Ritchie, Matthew E, Belz, Gabrielle T, Naik, Shalin H, Pellicci, Daniel G and Godfrey, Dale I (2020). A divergent transcriptional landscape underpins the development and functional branching of MAIT cells. The Journal of Immunology, 204 (1_Supplement), 223.8-223.8. doi: 10.4049/jimmunol.204.supp.223.8

A divergent transcriptional landscape underpins the development and functional branching of MAIT cells

2020

Journal Article

The molecular basis underpinning the potency and specificity of MAIT cell antigens

Awad, Wael, Ler, Geraldine J. M., Xu, Weijun, Keller, Andrew N., Mak, Jeffrey Y. W., Lim, Xin Yi, Liu, Ligong, Eckle, Sidonia B. G., Le Nours, Jérôme, McCluskey, James, Corbett, Alexandra J., Fairlie, David P. and Rossjohn, Jamie (2020). The molecular basis underpinning the potency and specificity of MAIT cell antigens. Nature Immunology, 21 (4), 400-411. doi: 10.1038/s41590-020-0616-6

The molecular basis underpinning the potency and specificity of MAIT cell antigens

2020

Journal Article

MAIT cells promote tumor initiation, growth and metastases via tumor MR1

Yan, Juming, Allen, Stacey, McDonald, Elizabeth, Das, Indrajit, Mak, Jeffrey Y. W., Liu, Ligong, Fairlie, David P., Meehan, Bronwyn S., Chen, Zhenjun, Corbett, Alexandra J., Varelias, Antiopi, Smyth, Mark J. and Teng, Michele W. L. (2020). MAIT cells promote tumor initiation, growth and metastases via tumor MR1. Cancer Discovery, 10 (1), 124-141. doi: 10.1158/2159-8290.cd-19-0569

MAIT cells promote tumor initiation, growth and metastases via tumor MR1

2019

Journal Article

A divergent transcriptional landscape underpins the development and functional branching of MAIT cells

Koay, H-. F., Su, S., Amann-Zalcenstein, D., Daley, S. R., Comerford, I., Miosge, L., Whyte, C. E., Konstantinov, I. E., d'Udekem, Y., Baldwin, T., Hickey, P. F., Berzins, S. P., Mak, J. Y. W., Sontani, Y., Roots, C. M., Sidwell, T., Kallies, A., Chen, Z., Nüssing, S., Kedzierska, K., Mackay, L. K., McColl, S. R., Deenick, E. K., Fairlie, D. P., McCluskey, J., Goodnow, C. C., Ritchie, M. E., Belz, G. T., Naik, S. H. ... Godfrey, D. I. (2019). A divergent transcriptional landscape underpins the development and functional branching of MAIT cells. Science Immunology, 4 (41) eaay6039, eaay6039. doi: 10.1126/sciimmunol.aay6039

A divergent transcriptional landscape underpins the development and functional branching of MAIT 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

    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

  • 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

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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