Our research is aimed at understanding how Plasmodium falciparum, the parasite that causes the most severe form of malaria, infects humans and causes disease.
We focus on three major aspects of malaria:
Australia, Griffith University, AC BSc (Hons), 1979
Australia, University of Melbourne, PhD, 1983
2001 Fellow, Australian Academy of Science
2002 Royal Society of Victoria 2001 Medallist for Scientific Research
2002 Commonwealth of Australia Centenary Medal
2006 ASBMB Lemberg Medal
2007-12 NHMRC Australia Fellowship
2010 Howard Taylor Ricketts Award from University of Chicago
2011 Fellow of Australian Society of Parasitology (FASP)
2011 Fellow of Australian Society of Microbiology (FASM)
2011 Fellow, The Royal Society (United Kingdom) (FRS)
2011 Eureka Prize for Infectious Diseases Research
2011 Research Excellence Award from National Health and Medical Research Council of Australia, Top ranked Research Fellow for 2010
2013 10 of the best National Health and Medical Research grants, Australia
2013 Victoria Prize, Victorian State Government
2014 Mahathir Prize, Mahathir Science Award Foundation, Malaysia
2014 Federation of Asian and Oceanian Biochemists and Molecular Biologists (FAOBMB) Award for Research Excellence
2014 Sornchai Looareesuwan Medal, Thailand
2015 The Alice and C. C. Wang Award in Molecular Parasitology from the American Society for Biochemistry and Molecular Biology (ASBMB)
2015 Research Excellence Award from National Health and Medical Research Council of Australia, Top ranked Program Grant for 2014
2016 Research Excellence Award from National Health and Medical Research Council of Australia, Top ranked Fellow for 2016
2017 Lifetime Achievement Award (BioMalPar, Europe)
2019 Companion of the Order of Australia
2020 communicating Fellow of the Royal Society of Edinburgh (commFRSE)
2021 CSL Florey Medal
2000 -05 Howard Hughes International Research Scholarship (USA),
2001-05 National Institutes of Health (USA), Principal Investigator,
2002 WHO/TDR, UNDP/World Bank/WHO (TDR),
2002-06 NHMRC Program Grant, Chief Investigator,
2002-06 The Wellcome Trust, Co-Investigator,
2005-07 Atlantic Philanthropies, Principal Investigator,
2005-07 European Commission 6th Framework Programme, Consortium Partner,
2005 WHO/TDR, EMBO, Howard Hughes Medical Institute,
2005-10 Grand Challenges for Global Health, Co-Investigator,
2006-10 Howard Hughes International Research Scholarship (USA),
2005-10 National Institutes of Health (USA), Principal Investigator,
2007-11 Australia Fellowship, Principal Investigator,
2008-10 NHMRC Project Grant, Chief Investigator
2007-11 Bill & Melinda Gates Foundation, Chief Investigator
2011-15 NHMRC Program Grant, Chief Investigator
2016-20 NHMRC Program Grant, Chief Investigator
2020-24 NHMRC L3 Investigator Grant
2015-16 WEHI Business Development Office Catalyst Fund
2016-17 Wellcome Trust Pathfinder Award,
2017-19 Wellcome Trust Seed Discovery Grant
2020-22 Wellcome Trust Drug Discovery Grant
2022-23 Wellcome Trust Drug Discovery Grant
2023 WEHI Ignition Fund
2001-2005, 2006-2010, 2010-2012, 2013-2017, Howard Hughes Medical Institute Fellowship
2007-2011, Bill and Melinda Gates Foundation
2002-2006,2006-2010,2011-2015,2016-2020, Program Grant, National Health and Medical Research Council
2005-2010 Principal Investigator, National Institutes of Health
2007-2011,Principal Investigator, Austrlia Fellowship
2009-2015, Program for Appropriate Technology in Heal/Malaria Vaccine Initiative/USAID
2011-2016, Program Grant, National Health and Medical Research Council
2016-2023 Wellcome Trust Seed Discovery Grants
2020-2024 L3 Investigator Grant, National Health and Medical Research Council
2010-2014, President, World Federation of Parasitology
Early Career Scientific Selection Committee, Howard Hughes Medical Institute
Advisory Board, Griffith University
Board of Review, Science journal
Promotions Board, QIMR Berghofer Institute
Rotarians Against Malaria: Rotary Australia World Community Service Ltd
Favuzza P, de Lera Ruiz M, Thompson JK, Triglia T, Ngo A, Steel RWJ, Vavrek M, Christensen J, Healer J, Boyce C, Guo Z, Hu M, Khan T, Murgolo N, Zhao L, Penington JS, Reaksudsan K, Jarman K, Dietrich MH, Richardson L, Guo KY, Lopaticki S, Tham WH, Rottmann M, Papenfuss T, Robbins JA, Boddey JA, Sleebs BE, Sabroux HJ, McCauley JA, Olsen DB, Cowman AF. Dual Plasmepsin-Targeting Antimalarial Agents Disrupt Multiple Stages of the Malaria Parasite Life Cycle. Cell Host Microbe. 2020 Feb 27. 27(4):642-658. (Citations 72; FWCI 4.75).
Wong W, Huang R, Menant S, Hong C, Sandow JJ, Birkinshaw RW, Healer J, Hodder AN, Kanjee U, Tonkin CJ, Heckmann D, Soroka V, Søgaard TMM, Jørgensen T, Duraisingh MT, Czabotar PE, de Jongh WA, Tham WH, Webb AI, Yu Z, Cowman AF. Structure of Plasmodium falciparum Rh5-CyRPA-Ripr invasion complex. Nature 2019 Jan;565(7737):118-121 (Citations 68; FWCI 3.49).
Regev-Rudzki N, Wilson DW, Carvalho TG, Sisquella X, Coleman BM, Rug M, Bursac D, Angrisano F, Gee M, Hill AF, Baum J, COWMAN AF. (2013). Cell-Cell Communication between Malaria-Infected Red Blood Cells via Exosome-like Vesicles. Cell. 153(5):1120-33 (Citations 530; FWCI 10.72).
Boddey JA, Hodder AN, Günther S, Gilson PR, Patsiouras H, Kapp EA, Pearce JA, de Koning-Ward TF, Simpson RJ, Crabb BS, COWMAN AF. (2010). An aspartyl protease directs malaria effector proteins to the host cell. Nature. 463:627-31 (Citations 352; FWCI 3.34).
Maier AG, Rug M, O’Neill MT, Brown M, Chakravorty S, Szestak T, Chesson J, Wu Y, Hughes K, Coppel RL, Newbold C, Beeson JG, Craig A, Crabb BS, COWMAN AF. (2008). Exported proteins required for virulence and rigidity of Plasmodium falciparum-infected human erythrocytes. Cell. 134(1):48-61 (Citations 554; FWCI 6.59).
Voss TS, Healer J, Marty AJ, Duffy MF, Thompson JK, Beeson JG, Reeder JC, Crabb BS, and COWMAN AF. (2006) A var gene promoter controls allelic exclusion of virulence genes in Plasmodium falciparum malaria. Nature 439:1004-1008 (Citations 323; FWCI 3.26).
Marti M, Good RT, Rug M, Knuepfer E, and COWMAN AF. (2004) Targeting malaria virulence and remodelling proteins to the host erythrocyte. Science 306:1930-1933 (Citations 1039; FWCI 5.54).
Reed MB, Saliba KJ, Caruana SR, Kirk K, and COWMAN AF. (2000) Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium falciparum. Nature 403:906-909 (Citations 1,076; FWCI 6.22).
Crabb BS, Cooke BM, Reeder JC, Waller RF, Caruana SR, Davern KM, Wickham ME, Brown GV, Coppel RL, and COWMAN AF. (1997) Targeted gene disruption shows that knobs enable malaria-infected cells to cytoadhere under physiological shear stresses. Cell 89:287-296 (Citations 554; FWCI 6.73).
Foote SJ, Kyle DE, Martin RK, Oduola AMJ, Forsyth KP, Kemp DJ, and COWMAN AF. (1990) Several alleles of the multidrug-resistance gene are closely linked to chloroquine resistance in Plasmodium falciparum. Nature 345:255-258 (Citations 738; FWCI not available)
Plasmodium falciparum, the deadliest malaria-causing parasite, invades and multiplies within human red blood cells. The parasite first attaches to the red blood cell and its proteins bind to the receptors on the red blood cell surface.
We try to understand the interactions between the parasite and the host cell that lead to successful invasion. Targeted protein depletion or antibody-mediated blocking of these interactions prevents the parasite from entering the red blood cell. Hence, it provides an attractive target for vaccine development.
Video of malaria parasites (blue) invading red blood cells (purple) and a Ca2+ signalling event (yellow), captured by lattice light sheet microscopy. Credit: Cindy Evelyn.
Team members: Stephen Scally, Pailene Lim, Benjamin Seager, Xiao Xiao
Once inside the red blood cell, the parasite modifies it so that the cell can provide a safe environment for parasite growth and replication.
To achieve this, the parasite produces a huge number of proteins which are then delivered to various destinations within the red blood cell. Inhibition of this protein trafficking kills the parasite, so we try to understand the mechanisms of this process and how we can stop it.
Team members: Danushka Marapana, Michał Pasternak, Julie Verhoef
New treatments for malaria are urgently needed due to rapidly developing resistance to existing medications. Our research team, in collaboration with Merck & Co., Inc., has identified a novel class of drug-like molecules that prevent malaria parasites growing in human red blood cells, known as dual plasmepsin IX/X inhibitors. With the support of a $4.6 million grant from the Wellcome Trust we have been working to improve these molecules and to test them against all parasite lifecycle stages. By characterising the drug targets, identifying their mode of action at all stages of the parasite lifecycle and studying their resistance profile, we can better understand the biology of the malaria parasite and how to kill it effectively with these new treatments.
Our dual plasmepsin inhibitors have been shown to robustly kill parasites at multiple stages of the parasite lifecycle and have a high barrier to resistance, making them ideal antimalarial drug candidates. As a result, our lead drug candidate is currently undergoing Phase I clinical trials in humans, and has the potential to become a new antimalarial drug, with the hope of contributing to the eradication of malaria.
Team members:Paola Favuzza, Tony Hodder, Josephine Palandri, Tup Reaksudsan, Tony Triglia
Malaria-causing parasites are transmitted by mosquitoes that have fed on the blood of infected individuals. The mosquito is infected with parasite gametocytes, which undergo sexual reproduction inside the mosquito and give rise to sporozoites. Sporozoites reside in the salivary gland of the mosquito and are able to invade human hepatocytes when the mosquito feeds again.
Our lab tries to understand these processes and how to block them.
We have identified enzymes required for sporozoite formation and are now trying to understand their function. We are also interested in innovative ways to limit malaria transmission.
WEHI’s mosquito insectary enables us to conduct research on malaria transmission.
Team members: Tup Reaksudsan, Julie Healer, Melissa Hobbs
Protein degradation, rather than inhibition, is a potent strategy for disrupting protein function. PROTACs are drugs that hijack the cell’s own ubiquitination machinery to degrade pathogenic proteins.
Using malaria parasite-specific PROTACs and by improving our understanding of the parasites own protein degradation system, we aim to destabilise functions essential for parasite survival in humans. By their unique mechanism of action, PROTACs can also bypass traditional drug resistance pathways.
To achieve these aims we will be using a combination of cutting-edge CRISPR/Cas9 mediated gene-editing of human malaria parasites, chemical biology, and structural biology.
Team members: Danushka Marapana, Sachin Khurana, Cary Lang
To better understand core processes regulating malaria parasite transmission to mosquitoes and its development at the host-vector interface we use functional proteomics approaches, including Thermal Proteome Profiling (TPP) and Limited Proteolysis Mass Spectrometry (Lip-MS). TPP and Lip-MS allow proteome-wide readout of protein stability, which is influenced by protein interactions with diverse physiological ligands, other proteins or structural modifications. We further leverage these orthogonal approaches for drug target-identification studies and characterisation of the mechanism of action of transmission-blocking antimalarials.
Team members: Jerzy Dziekan