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Diseases
  • Infection and Immunity

About

Our research is aimed at understanding the unique biology of the malaria parasite Plasmodium falciparum, with a particular focus on virulence and transmission.

We are investigating:
– How parasites renovate their RBC home to drive virulence and transmission
– How the parasite makes the banana-shaped sexual blood stage gametocyte
– How this shape helps them survive in the host and be efficiently transmitted
– How parasites behave inside the human host in vivo
– How effective specific drugs and vaccines are at blocking transmission of gametocytes from infected humans to Anopheles mosquitos.
– In these projects, we will use CRISPR gene editing to create transgenic malaria parasites, which we will study by combing proteomics, molecular and cellular biology techniques with super resolution microscopy to define the molecular players driving gametocyte development and transmission.

This in vitro work will be complimented by ex vivo examination of samples from experimental human malaria infection studies, which are focused on identifying and confirming the activity of candidate transmission blocking drugs and vaccines.

A combined in vitro and in vivo approach to understanding how gametocytes mature will inform the development of effective means of combating this debilitating disease.

Professor McCarthy holds a joint appointment as Director of the Victorian Infectious Diseases Service at the Royal Melbourne Hospital, and Professor of Medicine at the Doherty Institute where he leads the Translational Models of Infectious Diseases group that focusses on human infection challenge models to develop drugs and vaccines.

Publications

Selected publications from Prof James McCarthy

Williams E, Hocking JS, Fairley CK, Chen MY, Williamson DA, McCarthy JS, Jamrozik E. Rationale and Ethical Assessment of an Oropharyngeal Gonorrhoea Controlled Human Infection Model. The Journal of Infectious Diseases. 2025;:10.1093/infdis/jiaf029

Abd-Rahman AN, Kaschek D, Kümmel A, Webster R, Potter AJ, Odedra A, Woolley SD, Llewellyn S, Webb L, Marquart L, Chalon S, Gaaloul ME, McCarthy JS, Möhrle JJ, Barber BE. Characterizing the pharmacological interaction of the antimalarial combination artefenomel-piperaquine in healthy volunteers with induced blood-stage Plasmodium falciparum to predict efficacy in patients with malaria. BMC Medicine. 2024;22(1):10.1186/s12916-024-03787-0

Mukhiya R, Fleischmann WA, Loughland JR, Chan J-A, de Labastida Rivera F, Andrew D, Beeson JG, McCarthy JS, Barber BE, Lopez JA, Engwerda C, Thomson-Luque R, Boyle MJ. Heterogeneity of the human immune response to malaria infection and vaccination driven by latent cytomegalovirus infection. EBioMedicine. 2024;109:10.1016/j.ebiom.2024.105419

Persson KEM, Horton JL, Kurtovic L, McCarthy JS, Anders RF, Beeson JG. Declining Antibody Affinity Over Time After Human Vaccination With a Plasmodium falciparum Merozoite Vaccine Candidate. The Journal of Infectious Diseases. 2024;230(3):10.1093/infdis/jiae259

Tully MK, Dini S, Flegg JA, McCarthy JS, Price DJ, Simpson JA. Evaluation of a Bayesian hierarchical pharmacokinetic–pharmacodynamic model for predicting parasitological outcomes in Phase 2 studies of new antimalarial drugs. Antimicrobial Agents and Chemotherapy. 2024;68(9):10.1128/aac.00863-24

Puchner KP, Bottazzi ME, Periago V, Grobusch M, Maizels R, McCarthy J, Lee B, Gaspari E, Diemert D, Hotez P. Vaccine value profile for Hookworm. Vaccine. 2024;42(19):10.1016/j.vaccine.2023.05.013

Woolley SD, Grigg MJ, Marquart L, Gower JSE, Piera K, Nair AS, Amante FM, Rajahram GS, William T, Frazer DM, Chalon S, McCarthy JS, Anstey NM, Barber BE. Longitudinal changes in iron homeostasis in human experimental and clinical malaria. EBioMedicine. 2024;105:10.1016/j.ebiom.2024.105189

Muhi S, Buultjens AH, Porter JL, Marshall JL, Doerflinger M, Pidot SJ, O’Brien DP, Johnson PDR, Lavender CJ, Globan M, McCarthy J, Osowicki J, Stinear TP. Mycobacterium ulcerans challenge strain selection for a Buruli ulcer controlled human infection model. PLOS Neglected Tropical Diseases. 2024;18(5):10.1371/journal.pntd.0011979

Cao P, Kho S, Grigg MJ, Barber BE, Piera KA, William T, Poespoprodjo JR, Jang IK, Simpson JA, McCaw JM, Anstey NM, McCarthy JS, Britton S. Characterisation of Plasmodium vivax lactate dehydrogenase dynamics in P. vivax infections. Communications Biology. 2024;7(1):10.1038/s42003-024-05956-6

Williams E, Seib KL, Fairley CK, Pollock GL, Hocking JS, McCarthy JS, Williamson DA. Neisseria gonorrhoeae vaccines: a contemporary overview. Clinical Microbiology Reviews. 2024;37(1):10.1128/cmr.00094-23

Lab research projects

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