Wai-Hong Tham

Wai-Hong Tham is a Malaysian associate professor at the University of Melbourne and the Walter and Eliza Hall Institute of Medical Research (WEHI), and joint head of the division of Infectious Disease and Immune Defense.[1][2] She researches the molecular biology of the malaria parasite Plasmodium vivax.

Education

Tham was involved in work in 2000 with the lab of Barbara Baker on the tobacco mosaic virus resistance gene N in tobacco plants at University of California, Berkeley, using deletion studies to identify important amino acids in the structure of the protein to fight off the virus.[3] Tham was awarded her BA at University of California, Berkeley and her PhD at Princeton University with Virginia Zakian.[1][4] During her PhD Tham studied telomeres of yeast, showing that the localisation of the left telomere of chromosome IV at the periphery of the nuclear membrane was essential for, but not sufficient, to prevent gene expression.[5]

Career

Tham continued to work on yeast for her next project in the lab of Angelika Amon; using strains with individual genes deleted to identify genes involved in the separation of chromosomes during meiosis. Disruption of these genes in the deletion strains led to nondisjunction.[6] Tham also participated in identifying the protein FPR3 as a member of the recombination checkpoint program during meiosis.[7]

Tham first started working on malaria in the lab of Alan Cowman at WEHI. Here she identified the human red blood cell protein complement-receptor 1 (CR1) as the binding partner for the Plasmodium falciparum (the major human malaria) invasion protein Rh4.[8] Her further work in the same lab found the binding sites on the CR1 peptide for Rh4, and proved that phosphorylation of the cytoplasmic tails of Rh4 and other invasion proteins (sections of surface membrane proteins inside the cell) were essential for the malaria parasite to be able to penetrate red blood cells.[9][10]

In 2018, Tham's lab proved that the P. vivax reticulocyte-binding protein binds the human transferrin receptor 1 protein in order to invade early red blood cells (reticulocytes).[11][12][13] The same year, following on from this work, Tham's lab published a cryo-EM structure of the two proteins complexed together.[14][15][16] This structure showed where antibody binding sites can obstruct the interaction and prevent host cell invasion.[14][15]

Awards and accolades

Tham was named a Howard Hughes Medical Institute-Wellcome Trust International Research scholar in 2017.[4][17][18] In 2018 the WEHI institute awarded Tham the Burnet Prize for work on the binding of P. vivax parasites and red blood cells, and the University of Melbourne awarded her the David Syme Research Prize.[2][19] In 2019 Tham was a member of a team of P. vivax researchers from WEHI awarded the Australian Museum Eureka Prize.[20][21] The 2020 International Prize from the Biochemical Society was awarded to Tham.[22]

References
  1. "People: Wai-Hong Tham". WEHI. 15 July 2019. Retrieved 10 Dec 2019.
  2. Holland, Daryl (2018-09-13). "Associate Professor Wai-Hong Tham wins 2018 David Syme Research Prize". Faculty of Science. Retrieved 2019-12-10.
  3. Dinesh-Kumar, S. P.; Tham, Wai-Hong; Baker, Barbara J. (2000-12-19). "Structure–function analysis of the tobacco mosaic virus resistance gene N". Proceedings of the National Academy of Sciences. 97 (26): 14789–14794. doi:10.1073/pnas.97.26.14789. ISSN 0027-8424. PMC 18997. PMID 11121079.
  4. epaine (2017-05-19). "Former graduate student Wai-Hong Tham named International Research Scholar". molbio.princeton.edu. Retrieved 2019-12-10.
  5. Tham, Wai-Hong; Wyithe, J. Stuart B.; Ferrigno, Paul Ko; Silver, Pamela A.; Zakian, Virginia A. (2001-07-01). "Localization of Yeast Telomeres to the Nuclear Periphery Is Separable from Transcriptional Repression and Telomere Stability Functions". Molecular Cell. 8 (1): 189–199. doi:10.1016/S1097-2765(01)00287-8. ISSN 1097-2765. PMID 11511372.
  6. Marston, Adele L.; Tham, Wai-Hong; Shah, Hiral; Amon, Angelika (2004-02-27). "A Genome-Wide Screen Identifies Genes Required for Centromeric Cohesion". Science. 303 (5662): 1367–1370. doi:10.1126/science.1094220. ISSN 0036-8075. PMID 14752166.
  7. Hochwagen, Andreas; Tham, Wai-Hong; Brar, Gloria A.; Amon, Angelika (2005-09-23). "The FK506 Binding Protein Fpr3 Counteracts Protein Phosphatase 1 to Maintain Meiotic Recombination Checkpoint Activity". Cell. 122 (6): 861–873. doi:10.1016/j.cell.2005.07.010. ISSN 0092-8674. PMID 16179256.
  8. Tham, Wai-Hong; Wilson, Danny W.; Lopaticki, Sash; Schmidt, Christoph Q.; Tetteh-Quarcoo, Patience B.; Barlow, Paul N.; Richard, Dave; Corbin, Jason E.; Beeson, James G.; Cowman, Alan F. (2010-10-05). "Complement receptor 1 is the host erythrocyte receptor for Plasmodium falciparum PfRh4 invasion ligand". Proceedings of the National Academy of Sciences. 107 (40): 17327–17332. doi:10.1073/pnas.1008151107. ISSN 0027-8424. PMC 2951459. PMID 20855594.
  9. Tham, Wai-Hong; Schmidt, Christoph Q.; Hauhart, Richard E.; Guariento, Mara; Tetteh-Quarcoo, Patience B.; Lopaticki, Sash; Atkinson, John P.; Barlow, Paul N.; Cowman, Alan F. (2011-08-18). "Plasmodium falciparum uses a key functional site in complement receptor type-1 for invasion of human erythrocytes". Blood. 118 (7): 1923–1933. doi:10.1182/blood-2011-03-341305. ISSN 0006-4971. PMC 3158720. PMID 21685372.
  10. Tham, Wai-Hong; Lim, Nicholas T. Y.; Weiss, Greta E.; Lopaticki, Sash; Ansell, Brendan R. E.; Bird, Megan; Lucet, Isabelle; Dorin-Semblat, Dominique; Doerig, Christian; Gilson, Paul R.; Crabb, Brendan S. (2015-12-22). "Plasmodium falciparum Adhesins Play an Essential Role in Signalling and Activation of Invasion into Human Erythrocytes". PLOS Pathogens. 11 (12): e1005343. doi:10.1371/journal.ppat.1005343. ISSN 1553-7374. PMC 4687929. PMID 26694741.
  11. Gruszczyk, Jakub; Kanjee, Usheer; Chan, Li-Jin; Menant, Sébastien; Malleret, Benoit; Lim, Nicholas T. Y.; Schmidt, Christoph Q.; Mok, Yee-Foong; Lin, Kai-Min; Pearson, Richard D.; Rangel, Gabriel (2018-01-05). "Transferrin receptor 1 is a reticulocyte-specific receptor for Plasmodium vivax". Science. 359 (6371): 48–55. doi:10.1126/science.aan1078. ISSN 0036-8075. PMC 5788258. PMID 29302006.
  12. "Aussies solve malaria mystery". www.theaustralian.com.au. 2018-01-04. Retrieved 2019-12-10.
  13. "Aussie breakthrough could lead to malaria vaccine - 9News". www.9news.com.au. Retrieved 2019-12-10.
  14. Gruszczyk, Jakub; Huang, Rick K.; Chan, Li-Jin; Menant, Sébastien; Hong, Chuan; Murphy, James M.; Mok, Yee-Foong; Griffin, Michael D. W.; Pearson, Richard D.; Wong, Wilson; Cowman, Alan F. (July 2018). "Cryo-EM structure of an essential Plasmodium vivax invasion complex". Nature. 559 (7712): 135–139. doi:10.1038/s41586-018-0249-1. ISSN 1476-4687. PMID 29950717.
  15. First malaria-human contact mapped with Nobel Prize-winning technology, retrieved 2019-12-10
  16. Melbourne, Andrew Trounson, University of (2018-06-28). "Exposing malaria's atomic machinery". Pursuit. Retrieved 2019-12-10.
  17. "Philanthropies Select 41 Scientists as International Research Scholars". HHMI.org. Retrieved 2019-12-10.
  18. "Health Victoria News - Department of Health Victoria Australia". www.health.vic.gov.au. Retrieved 2019-12-10.
  19. "Celebrating Discovery 2018". WEHI. Dec 2018. Retrieved 10 Dec 2019.
  20. "Malaria team named 2019 Eureka Prize winner". WEHI - Illuminate. Retrieved 10 Dec 2019.
  21. "Eureka Prize for Institute malaria team". Mirage News. 2019-08-28. Retrieved 2019-12-10.
  22. "2020 Awards Winners". Biochemistry Society. Retrieved 10 Dec 2019.
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