Professor Wai-Hong Tham received her PhD from Princeton University. She is a Lab Head and co-Chair of the Biologics Initiative at WEHI.
Her lab has made fundamental discoveries in novel host-pathogen interactions and examined their molecular and structural mechanisms to drive rational design of new therapies against malaria. Her lab studies parasite adhesins required for entry into human red cells, parasite surface proteins that bind to human complement proteins for immune evasion and novel parasite proteins involved in fertilisation.
The overarching aim is to rationally design and generate new inhibitors or antibodies that block these interactions and stop recurrent malaria infection in humans and block transmission from mosquitoes. Our work intersects with the fields of structural biology, nanobody technology, immuno-epidemiology and molecular parasitology.
United States of America, Princeton University, PhD
United States of America, UC Berkeley, BA
Australian National University (Nov 2023)
2023 Victorian Honour Roll of Women, Change Agent
2023 Bancroft-Mackerras Medal for Excellence, Australian Society of Parasitology
2020 International Award, Biochemical Society, UK
2022 and 2018 Elizabeth Blackburn Biomedical Fellowship, NHMRC
2019 and 2011 Eureka Prize for Infectious Diseases Research (team prize)
2018 Burnet Prize
2017 David Syme Research Prize
2017 HHMI-Wellcome International Research Scholar
2023 mRNA Victoria Research Acceleration Fund
2023 Leadership 2, Investigator Grant
2022 Australia-India Strategic Research Fund
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
Scientific Advisory Group, mRNA Victoria
Scientific Advisory Committee, Victorian mRNA Innovation Hub (VMIH)
Scientific Advisory Board, Center of Structural Systems Biology, Germany
Editorial Board Member, Journal of Biological Chemistry
Editorial Board Member, FEMS Microbes
Dietrich MH, Gabriela M, Reaksudsan K, Dixon MWA, Chan LJ, Adair A, Trickey S, O’Neill MT, Tan LL, Lopaticki S, Healer J, Keremane S, Cowman A, Tham WH. Nanobodies against Pfs230 block Plasmodium falciparum transmission. Biochem J. 2022: BCJ20220554. PMID: 36520108
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
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.
Surface-associated proteins play critical roles in the Plasmodium parasite life cycle and are major targets for vaccine development. The 6-cysteine (6-cys) protein family is expressed in stage-specific manner throughout the parasite life cycle and conserved across Plasmodium species, but the precise function of many family members is still unknown.
The main aims of this project are to dissect the roles of 6-cys family during the parasite life cycle. We have nanobodies against several 6-cys proteins to examine the cellular localization, to identify interacting partners and neutralizing antibodies against parasite blood stage invasion and transmission studies.
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.
Nanobodies are single domain antibodies isolated from camelids or cartilaginous fish. They are the smallest naturally derived antigen-binding fragment and only one-tenth the size of conventional antibodies. Nanobodies are used as therapeutics and research tools due to their small size, high antigen binding affinity, solubility and increased stability across temperature and pH.
This project will involve characterization of nanobodies against malaria proteins to identify antibodies that effectively inhibit parasite fertilisation and subsequent transmission from mosquito to human. We will use a wide range of biochemical, structural and molecular techniques to characterize the mechanism of inhibition. The results from this project identify new potential therapeutics to block transmission.