Prof Wai-Hong Tham, Lab Head | WEHI Researcher Profile

Q: Complement evasion strategies of malaria parasites

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.

Q: Pathways of entry for malaria parasite into human blood

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.

Q: Human monoclonal antibodies against malaria infection

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.

About

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.

Education

Joint appointments

Grants and funding

Publications

Selected publications from Prof Wai-Hong Tham

D J, Krauss L, Smith L, D’Andrea L, Chan L-J, Abraham A, Kiernan-Walker N, Mazhari R, Lamont M, Lim PS, Sattabongkot J, Lacerda MV, Wini L, Mueller I, Longley RJ, Pymm P, Fleishman SJ, Tham W-H. Stabilized designs of the malaria adhesin protein PvRBP2b for use as a potential diagnostic for Plasmodium vivax. Journal of Biological Chemistry. 2025;301(3):10.1016/j.jbc.2025.108290

Winnicki AC, Dietrich MH, Yeoh LM, Carias LL, Roobsoong W, Drago CL, Malachin AN, Redinger KR, Feufack-Donfack LB, Baldor L, Jung NC, McLaine OS, Skomorovska-Prokvolit Y, Orban A, Opi DH, Kirtley P, Nielson K, Aleshnick M, Zanghi G, Rezakhani N, Vaughan AM, Wilder BK, Sattabongkot J, Tham W-H, Popovici J, Beeson JG, Bosch J, King CL. Potent AMA1-specific human monoclonal antibody against Plasmodium vivax Pre-erythrocytic and Blood Stages. Nature Communications. 2024;15(1):10.1038/s41467-024-53848-4

Dans MG, Boulet C, Watson GM, Nguyen W, Dziekan JM, Evelyn C, Reaksudsan K, Mehra S, Razook Z, Geoghegan ND, Mlodzianoski MJ, Goodman CD, Ling DB, Jonsdottir TK, Tong J, Famodimu MT, Kristan M, Pollard H, Stewart LB, Brandner-Garrod L, Sutherland CJ, Delves MJ, McFadden GI, Barry AE, Crabb BS, de Koning-Ward TF, Rogers KL, Cowman AF, Tham W-H, Sleebs BE, Gilson PR. Author Correction: Aryl amino acetamides prevent Plasmodium falciparum ring development via targeting the lipid-transfer protein PfSTART1. Nature Communications. 2024;15(1):10.1038/s41467-024-52849-7

Winnicki AC, Dietrich MH, Yeoh LM, Carias LL, Roobsoong W, Drago CL, Malachin AN, Redinger KR, Feufack-Donfack LB, Baldor L, Jung NC, McLaine OS, Skomorovska-Prokvolit Y, Orban A, Opi DH, Kirtley P, Nielson K, Aleshnick M, Zanghi G, Rezakhani N, Vaughan AM, Wilder BK, Sattabongkot J, Tham W-H, Popovici J, Beeson JG, Bosch J, King CL. Potent AMA1-specific human monoclonal antibody against P. vivax Pre-erythrocytic and Blood Stages. 2024;5(02-16):10.1101/2024.02.07.579302

Anstey NM, Tham W-H, Shanks GD, Poespoprodjo JR, Russell BM, Kho S. The biology and pathogenesis of vivax malaria. Trends in Parasitology. 2024;40(7):10.1016/j.pt.2024.04.015

Dans MG, Boulet C, Watson GM, Nguyen W, Dziekan JM, Evelyn C, Reaksudsan K, Mehra S, Razook Z, Geoghegan ND, Mlodzianoski MJ, Goodman CD, Ling DB, Jonsdottir TK, Tong J, Famodimu MT, Kristan M, Pollard H, Stewart LB, Brandner-Garrod L, Sutherland CJ, Delves MJ, McFadden GI, Barry AE, Crabb BS, de Koning-Ward TF, Rogers KL, Cowman AF, Tham W-H, Sleebs BE, Gilson PR. Aryl amino acetamides prevent Plasmodium falciparum ring development via targeting the lipid-transfer protein PfSTART1. Nature Communications. 2024;15(1):10.1038/s41467-024-49491-8

Adair A, Tan LL, Feng J, Girkin J, Bryant N, Wang M, Mordant F, Chan L-J, Bartlett NW, Subbarao K, Pymm P, Tham W-H. Human coronavirus OC43 nanobody neutralizes virus and protects mice from infection. Journal of Virology. 2024;98(6):10.1128/jvi.00531-24

Nguyen W, Boulet C, Dans MG, Loi K, Jarman KE, Watson GM, Tham W-H, Fairhurst KJ, Yeo T, Fidock DA, Wittlin S, Chowdury M, de Koning-Ward TF, Chen G, Yan D, Charman SA, Baud D, Brand S, Jackson PF, Cowman AF, Gilson PR, Sleebs BE. Activity refinement of aryl amino acetamides that target the P. falciparum STAR-related lipid transfer 1 protein. European Journal of Medicinal Chemistry. 2024;270:10.1016/j.ejmech.2024.116354

Chen J, Neil JA, Tan JP, Rudraraju R, Mohenska M, Sun YBY, Walters E, Bediaga NG, Sun G, Zhou Y, Li Y, Drew D, Pymm P, Tham WH, Wang Y, Rossello FJ, Nie G, Liu X, Subbarao K, Polo JM. A placental model of SARS-CoV-2 infection reveals ACE2-dependent susceptibility and differentiation impairment in syncytiotrophoblasts. Nature Cell Biology. 2023;25(8):10.1038/s41556-023-01182-0

Haycroft ER, Davis SK, Ramanathan P, Lopez E, Purcell RA, Tan LL, Pymm P, Wines BD, Hogarth PM, Wheatley AK, Juno JA, Redmond SJ, Gherardin NA, Godfrey DI, Tham W-H, Selva KJ, Kent SJ, Chung AW. Antibody Fc-binding profiles and ACE2 affinity to SARS-CoV-2 RBD variants. Medical Microbiology and Immunology. 2023;212(4):10.1007/s00430-023-00773-w