Wai-Hong Tham

Academic Lead, ANU Nanobody Facility (BRF)

Group membership

Group Leader, Tham Group

Wai-Hong Tham received her PhD from Princeton University and her B.A. from University of California, Berkeley. She also holds a joint appointment at WEHI as a Lab Head in the Infectious Diseases and Immune Defense Division and is co-Chair of the WEHI Biologics Initiative.

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.

Research interests

To understand mechanisms of malaria parasite entry and fertilisation for the development of novel interventions to stop infection and transmission of the malaria parasites.

Selected publications:

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.

Link to ORCID Profile: https://orcid.org/0000-0001-7950-8699