Dr Jeffrey Mak

Research Officer

Institute for Molecular Bioscience
j.mak@imb.uq.edu.au
+61 7 334 62988

Overview

Jeffrey Mak (PhD) is an organic chemist at the Institute for Molecular Bioscience. In his research, he seeks to apply a mechanistic approach to scientific problem solving. His publications cover a range of disciplines such as biological and medicinal chemistry, total synthesis, and physical organic chemistry. In 2017, Dr Mak was selected as a CAS SciFinder Future Leader by the Chemical Abstract Service (a division of the American Chemical Society).

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. In recent years, his research has particularly focused on mucosal associated invariant T (MAIT) cells, which are a newly characterised subset of immune cells important in antibacterial defence. 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). In 2018, Dr Mak was chief investigator on a UQ Early Career Researcher Grant for developing new drug leads that target MAIT cells.

Dr Mak has co-supervised eight student projects, and contributes to the undergraduate courses Advanced Organic Chemistry (CHEM3001) and Experimental Chemistry (CHEM2054). He has also served as an ACS Wikipedia Fellow to systematically improve the chemistry and scientific content on Wikipedia (2018).

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. In the Fairlie group, we aim to use our collective expertise to develop drugs as potential treatments for 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 sixteen labs worldwide and have enabled >15 papers in the MAIT cell field.

Selected talks

  • 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)
  • Brisbane Life Science Symposium, Brisbane, Australia, 2016
  • Invited: ARC Centre of Excellence in Advanced Molecular Imaging Summit, Melbourne, Australia, 2015

Selected awards

Dr Mak has received ten awards/honours since 2007, including:

Qualifications

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

Publications

View all Publications

Grants

View all Grants

Supervision

  • Doctor Philosophy

View all Supervision

Publications

Featured Publications

Book Chapter

  • Mak, Jeffrey Y. W., Xu, Weijun and Fairlie, David P. (2017). Thiazoles in peptides and peptidomimetics. In William D. Lubell (Ed.), Peptidomimetics I (pp. 235-266) Cham, Switzerland: Springer. doi:10.1007/7081_2015_176

Journal Article

  • Juno, Jennifer A., Wragg, Kathleen M., Amarasena, Thakshila, Meehan, Bronwyn S., Mak, Jeffrey Y. W., Liu, Ligong, Fairlie, David P., McCluskey, James, Eckle, Sidonia B. G. and Kent, Stephen J. (2019) MAIT cells upregulate α4β7 in response to acute simian immunodeficiency virus/simian HIV infection but are resistant to peripheral depletion in pigtail macaques. The Journal of Immunology, 202 7: ji1801405-2120. doi:10.4049/jimmunol.1801405

  • Wang, Huimeng, D’Souza, Criselle, Lim, Xin Yi, Kostenko, Lyudmila, Pediongco, Troi J., Eckle, Sidonia B. G., Meehan, Bronwyn S., Shi, Mai, Wang, Nancy, Li, Shihan, Liu, Ligong, Mak, Jeffrey Y. W., Fairlie, David P., Iwakura, Yoichiro, Gunnersen, Jennifer M., Stent, Andrew W., Godfrey, Dale I., Rossjohn, Jamie, Westall, Glen P., Kjer-Nielsen, Lars, Strugnell, Richard A., McCluskey, James, Corbett, Alexandra J., Hinks, Timothy S. C. and Chen, Zhenjun (2018) MAIT cells protect against pulmonary Legionella longbeachae infection. Nature Communications, 9 1: 3350. doi:10.1038/s41467-018-05202-8

  • Kjer-Nielsen, Lars, Corbett, Alexandra J., Chen, Zhenjun, Liu, Ligong, Mak, Jeffrey Y. W., Godfrey, Dale I., Rossjohn, Jamie, Fairlie, David P., McCluskey, James and Eckle, Sidonia B. G. (2018) An overview on the identification of MAIT cell antigens. Immunology and Cell Biology, 96 6: 573-587. doi:10.1111/imcb.12057

  • Varelias, Antiopi, Bunting, Mark D., Ormerod, Kate L., Koyama, Motoko, Olver, Stuart D., Straube, Jasmin, Kuns, Rachel D., Robb, Renee J., Henden, Andrea S., Cooper, Leanne, Lachner, Nancy, Gartlan, Kate H., Lantz, Olivier, Kjer-Nielsen, Lars, Mak, Jeffrey Y. W., Fairlie, David P., Clouston, Andrew D., McCluskey, James, Rossjohn, Jamie, Lane, Steven W., Hugenholtz, Philip and Hill, Geoffrey R. (2018) Recipient mucosal-associated invariant T cells control GVHD within the colon. Journal of Clinical Investigation, 128 5: 1919-1936. doi:10.1172/JCI91646

  • D'Souza, Criselle, Pediongco, Troi, Wang, Huimeng, Scheerlinck, Jean-Pierre Y., Kostenko, Lyudmila, Esterbauer, Robyn, Stent, Andrew W., Eckle, Sidonia B. G., Meehan, Bronwyn S., Strugnell, Richard A., Cao, Hanwei, Liu, Ligong, Mak, Jeffrey Y. W., Lovrecz, George, Lu, Louis, Fairlie, David P., Rossjohn, Jamie, McCluskey, James, Every, Alison L., Chen, Zhenjun and Corbett, Alexandra J. (2018) Mucosal-Associated Invariant T Cells Augment Immunopathology and Gastritis in Chronic Helicobacter pylori Infection. Journal of Immunology, 200 5: 1901-1916. doi:10.4049/jimmunol.1701512

  • Stoermer, Martin J., Wickramasinghe, Wasantha A., Byriel, Karl A., Hockless, David C. R., Skelton, Brian W., Sobolev, Alexandre N., White, Allan H., Mak, Jeffrey Y. W. and Fairlie, David P. (2017) Stereoelectronic Effects on Dienophile Separation Influence the Diels–Alder Synthesis of Molecular Clefts. European Journal of Organic Chemistry, 2017 45: 6793-6796. doi:10.1002/ejoc.201701319

  • 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 14599. doi:10.1038/ncomms14599

  • Keller, Andrew N., Eckle, Sidonia B. G., Xu, Weijun, Liu, Ligong, Hughes, Victoria A., Mak, Jeffrey Y. W., Meehan, Bronwyn S., Pediongco, Troi, Birkinshaw, Richard W., Chen, Zhenjun, Wang, Huimeng, D'Souza, Criselle, Kjer-Nielsen, Lars, Gherardin, Nicholas A., Godfrey, Dale I., Kostenko, Lyudmila, Corbett, Alexandra J., Purcell, Anthony W., Fairlie, David P., McCluskey, James and Rossjohn, Jamie (2017) Drugs and drug-like molecules can modulate the function of mucosal-associated invariant T cells. Nature Immunology, 18 4: 402-411. doi:10.1038/ni.3679

  • Yau, Mei-Kwan, Liu, Ligong, Suen, Jacky Y., Lim, Junxian, Lohman, Rink-Jan, Jiang, Yuhong, Cotterell, Adam J., Barry, Grant D., Mak, Jeffrey Y. W., Vesey, David A., Reid, Robert C. and Fairlie, David P. (2016) PAR2 modulators derived from GB88. ACS Medicinal Chemistry Letters, 7 12: 1179-1184. doi:10.1021/acsmedchemlett.6b00306

  • Eckle, Sidonia B.G., Corbett, Alexandra J., Keller, Andrew, Chen, Zhenjun, Godfrey, Dale I., Liu, Ligong, Mak, Jeffrey Y. W., Fairlie, David P., Rossjohn, Jamie and McCluskey, James (2015) Recognition of Vitamin B precursors and byproducts by Mucosal Associated Invariant T cells. The Journal of Biological Chemistry, 290 51: 30204-30211. doi:10.1074/jbc.R115.685990

  • 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

  • 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

  • Mak, Jeffrey Y. W. and Williams, Craig M. (2012) Erratum: Enantioselective total synthesis of ()-neovibsanin G and ()-14-epi-neovibsanin G (Chemical Communications (2012) (287-289) DOI: 10.1039/c1cc15995j)). Chemical Communications, 48 100: . doi:10.1039/c2cc90426h

  • Mak, Jeffrey Y. W. and Williams, Craig M. (2012) Key achievements in the total synthesis of vibsane-type diterpenoids. Natural Product Reports, 29 4: 440-448. doi:10.1039/c2np00067a

  • Mak, Jeffrey Y. W. and Williams, Craig M. (2012) Total synthesis of (-)-neovibsanin G and (-)-14-epi-neovibsanin G: Towards the synthesis of 15-O-methylneovibsanin F and 14-epi-15-O-methylneovibsanin F. European Journal of Organic Chemistry, 2012 10: 2001-2012. doi:10.1002/ejoc.201101796

  • 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

  • McGeary, Ross P., Vella, Peter, Mak, Jeffery Y. W., Guddat, Luke W. and Schenk, Gerhard (2009) Inhibition of purple acid phosphatase with alpha-alkoxynaphthylmethylphosphonic acids. Bioorganic & Medicinal Chemistry Letters, 19 1: 163-166. doi:10.1016/j.bmcl.2008.10.125

Conference Publication

  • Varelias, Antiopi, Bunting, Mark, Ormerod, Kate, Koyama, Motoko, Olver, Stuart, Straube, Jasmin, Kuns, Rachel, Robb, Renee, Henden, Andrea, Cooper, Leanne, Lachner, Nancy, Gartlan, Kate, Lantz, Olivier J., Kjer-Nielsen, Lars, Mak, Jeffrey, Fairlie, David, Clouston, Andrew, McCluskey, James, Rossjohn, Jamie, Lane, Steven, Hugenholtz, Phil and Hill, Geoff (2018). Recipient mucosal-associated invariant T cells control graft-versus-host-disease within the colon. In: Immunology Meeting, Austin Tx, (). 4-8 May 2018.

  • Stoermer, Martin J., Wickramasinghe, Wasantha A., Byriel, Karl A., Hockless, David C. R., Skelton, Brian W., Sobolev, Alexandre N., White, Alan H., Mak, Jeffrey Y. W. and Fairlie, David P. (2018). Stereoelectronic effects on dienophile separation influence the Diels–Alder synthesis of molecular clefts. In: 2018 Royal Society of Chemistry Twitter Conference, London, United Kingdom (held online), (). 6-7 March 2018.

  • Mak, Jeffrey, Xu, Weijun, Reid, Robert, Corbett, Alexandra, Meehan, Bronwyn, Wang, Huimeng, Chen, Zhenjun, Rossjohn, Jamie, McCluskey, James, Liu, Ligong and Fairlie, David (2017). Vitamin B2 related molecules that activate T cells. In: 254th National Meeting and Exposition of the American-Chemical-Society (ACS) on Chemistry's Impact on the Global Economy, Washington DC, USA, (). 20-24 August 2017.

  • Keller, A. N., Eckle, S. B. G., Xu, W., Liu, L., Hughes, V. A., Mak, J., Meehan, B., Pediongco, T., Birkinshaw, R. W., Chen, Z., Wang, H., Souza, C., Kostenko, L., Corbett, A. J., Purcell, A. W., Fairlie, D. P., McCluskey, J. and Rossjohn, J. (2016). Common drugs modulate mucosal-associated invariant T cell function. In: International Congress of Immunology (ICI), Melbourne, VIC, Australia, (257-257). 21-26 August 2016. doi:10.1002/eji.201670200

  • Eckle, S. B. G., Keller, A. N., Xu, W., Meehan, B., Pediongco, T., Liu, L., Hughes, V. A., Mak, J. Y. W., Birkinshaw, R. W., Chen, Z., Wang, H., D'Souza, C., Kostenko, L., Corbett, A. J., Purcell, A. W., Fairlie, D. P., Rossjohn, J. and McCluskey, J. (2016). Drugs/drug analogues modulate MAIT cell function in an MR1-dependent manner. In: International Congress of Immunology (ICI), Melbourne, VIC, Australia, (587-587). 21-26 August 2016. doi:10.1002/eji.201670200

  • McCluskey, J., Corbett, A. J., Eckle, S. B. G., Chen, Z., Wang, H., Sun, S., D'Souza, C., Kostenko, L., Reantragoon, R., Meehan, B., Birkinshaw, R. W., Liu, L., Patel, O., Mahony, J., Cao, H., Jackson, D., Williamson, N. A., Strugnell, R. A., Mak, J. Y. W., Van Sinderen, D., Fairlie, D. P., Kjer-Nielsen, L., Godfrey, D., I and Rossjohn, J. (2016). MAIT cells: Friend or Foe in recognising microbial vitamin metabolites presented by the MHC-I-related molecule MR1. In: International Congress of Immunology (ICI), Melbourne, Australia, (796-797). August 21-26, 2016. doi:10.1002/eji.201670200

Grants (Administered at UQ)

PhD and MPhil Supervision

Current Supervision