We have a strong interest in host-parasite interactions that govern successful malaria infection. In particular we study parasite proteins that are required for entry into red blood cells that are completely exposed to human immune system.
My lab combines molecular, cellular and structural biology methods with parasitology to study the mechanisms by which parasite proteins recognise and bind to human proteins. Using this information, we design and generate new inhibitors or antibodies that is able to block the interaction and hence, stop the recurrent infection in the host.
We work closely with partners in malaria endemic regions to ensure that our research remains relevant in combating this disease.
United States of America, Princeton University, PhD
United States of America, UC Berkeley, BA
2020 International Award, Biochemical Society, UK
2018 Elizabeth Blackburn Biomedical Fellowship, NHMRC
2018 Burnet Prize
2017 David Syme Research Prize
2017 HHMI-Wellcome International Research Scholar
2020 Anti-Viral Grant, Medical Research Future Fund
2020 Ideas Grant, National Health and Medical Research Council
2019 Project Grant, National Health and Medical Research Council
2018 Project Grant, National Health and Medical Research Council
2016 Project Grant, CIC National Health and Medical Research Council
Scientific Advisory Board, Center of Structural Systems Biology, Germany
Editorial Board Member, FEMS Microbes
2020 Chair, Malaria Gordon Research Conference
Scientific Advisory Board, Institut Pasteur du Cambodge
Independent Scientific Advisory Committee, MultiViVax
2016, 2017, 2018 Grant Review Panel member, National Health and Medical Research Council
2016, 2017 Editorial Board, Frontiers in Microbial Immunology
Pymm P, Adair A, Chan LJ, Cooney JP, Mordant FL, Allison CC, Lopez E, Haycroft ER, O’Neill MT, Tan LL, Dietrich MH, Drew D, Doerflinger M, Dengler MA, Scott NE, Wheatley AK, Gherardin NA, Venugopal H, Cromer D, Davenport MP, Pickering R, Godfrey DI, Purcell DFJ, Kent SJ, Chung AW, Subbarao K, Pellegrini M, Glukhova A, Tham WH. Nanobody cocktails potently neutralize SARS-CoV-2 D614G N501Y variant and protect mice. Proc Natl Acad Sci U S A. 2021; 118(19): e2101918118. PMID: 33893175
Chan LJ, Gandhirajan A, Carias LL, Dietrich MH, Vadas O, Visentin R, França CT, Menant S, Soldati-Favre D, Mueller I, King CL#, Tham WH#. Naturally acquired blocking human monoclonal antibodies to Plasmodium vivax reticulocyte binding protein 2b. Nat Commun. 2021;12(1):1538. PMID: 33750786
Dietrich MH, Chan LJ, Adair A, Keremane S, Pymm P, Lo AW, Cao YC, Tham WH. Nanobody generation and structural characterization of Plasmodium falciparum 6-cysteine protein Pf12p. Biochem J. 2021;478(3):579-595. PMID: 33480416
Gruszczyk J, Huang RK, Chan LJ, Menant S, Hong C, Murphy JM, Mok YF, Griffin MDW, Pearson RD, Wong W, Cowman AF, Yu Z, Tham WH. Cryo-EM structure of an essential Plasmodium vivax invasion complex. Nature. 2018 Jul;559(7712):135-139. doi: 10.1038/s41586-018-0249-1. Epub 2018 Jun 27. PubMed PMID: 29950717.
Gruszczyk J, Kanjee U, Chan LJ, Menant S, Malleret B, Lim NTY, Schmidt CQ, Mok YF, Lin KM, Pearson RD, Rangel G, Smith BJ, Call MJ, Weekes MP, Griffin MDW, Murphy JM, Abraham J, Sriprawat K, Menezes MJ, Ferreira MU, Russell B, Renia L, Duraisingh MT, Tham WH. Transferrin receptor 1 is a reticulocyte-specific receptor for Plasmodium vivax. Science. 2018 Jan 5;359(6371):48-55. doi:10.1126/science.aan1078. PubMed PMID: 29302006 | Read full text [http://science.sciencemag.org/cgi/content/full/359/6371/48?ijkey=lxl5gAQCnlUuA&keytype=ref&siteid=sci]
Gruszczyk J, Lim NT, Arnott A, He WQ, Nguitragool W, Roobsoong W, Mok YF, Murphy JM, Smith KR, Lee S, Bahlo M, Mueller I, Barry AE, Tham WH. Structurally conserved erythrocyte-binding domain in Plasmodium provides a versatile scaffold for alternate receptor engagement. Proc Natl Acad Sci U S A. 2016 Jan 12;113(2):E191-200. doi: 10.1073/pnas.1516512113. Epub 2015 Dec 29. PubMed PMID: 26715754; PubMed Central PMCID: PMC4720341.
Kennedy AT, Schmidt CQ, Thompson JK, Weiss GE, Taechalertpaisarn T, Gilson PR, Barlow PN, Crabb BS, Cowman AF, Tham WH. Recruitment of Factor H as a Novel Complement Evasion Strategy for Blood-Stage Plasmodium falciparum Infection. J Immunol. 2016 Feb 1;196(3):1239-48. doi: 10.4049/jimmunol.1501581. Epub 2015 Dec 23. PubMed PMID: 26700768.
Tham WH, Lim NT, Weiss GE, Lopaticki S, Ansell BR, Bird M, Lucet I, Dorin-Semblat D, Doerig C, Gilson PR, Crabb BS, Cowman AF. Plasmodium falciparum Adhesins Play an Essential Role in Signalling and Activation of Invasion into Human Erythrocytes. PLoS Pathog. 2015 Dec 22;11(12):e1005343. doi: 10.1371/journal.ppat.1005343. eCollection 2015 Dec. PubMed PMID: 26694741; PubMed Central PMCID: PMC4687929.
Tham WH, Kennedy AT. Malaria: a master lock for deadly parasites. Nature. 2015 Jun 11;522(7555):158-9. doi: 10.1038/522158a. PubMed PMID: 26062503.
Schmidt CQ, Kennedy AT, Tham WH. More than just immune evasion: Hijacking complement by Plasmodium falciparum. Mol Immunol. 2015 Sep;67(1):71-84. doi: 10.1016/j.molimm.2015.03.006. Epub 2015 Mar 26. Review. PubMed PMID: 25816986.
In the human host, complement regulators modulate the complement cascade to protect self-tissue from indiscriminate complement attack. Pathogens, on the other hand actively recruit host regulators with the foremost intention of inhibiting the complement cascade to prevent pathogen destruction. The acquisition of host complement regulators is the most widely used strategy for complement evasion among viruses, bacteria, fungi and parasites. This project will involve identifying which complement regulators are recruited by malaria parasites and how this prevents killing. It will also investigate the role of parasite surface proteins in recruitment of human complement regulators. This project will provide the first identification of complement evasion strategies employed by the malaria parasite.
Being an obligate intracellular parasite, malaria parasites have to invade red blood cells in order to survive within the human host. One essential step within invasion is the recognition of human red blood cells by malaria parasites, a process involving an intimate interaction between parasite adhesins and red blood cells receptors. This project will identify novel parasite adhesins involved in red blood cell recognition and how they function in the dynamic process of entry. We can exploit this information to rationally design inhibitors or antibodies to prevent malaria parasite invasion into human red blood cells.
Our lab is interested in identifying novel parasite adhesins involved in red blood cell recognition and how they function in the dynamic process of parasite entry.
This project will involve characterisation of human monoclonal antibodies to identify neutralising antibodies that effectively inhibit parasite invasion. We will use a wide range of biochemical, structural and molecular techniques to characterise the mechanism of inhibition. We can exploit this crucial information to rationally design a potential vaccine to prevent malaria parasite invasion into human red blood cells.