Professor Christian Engwerda studies the behaviour of T cells during parasitic infections. His group investigates how T cell responses are regulated during infection and uses this knowledge to develop new approaches to treat disease. Professor Engwerda established his laboratory at QIMR Berghofer in 2003 as a NHMRC career Development Fellow, after spending 8 years at the London School of Hygiene and Tropical Medicine. He is a NHMRC Senior Research Fellow and works with experimental models of malaria and leishmaniasis. In recent years, his group’s research has increasingly focused on studying samples from volunteers deliberately infected with parasites, as well as from malaria and leishmaniasis patients. The goal of his research is to improve anti-parasitic immunity using host-directed treatments in combination with vaccines and/or anti-parasitic drugs. He is also using his discoveries in parasitic diseases to guide development of new treatments for chronic inflammatory diseases.
Our goal is to understand the immunoregulatory mechanisms employed by CD4+ T cells during parasitic diseases so that we can manipulate them for clinical advantage. We use pre-clinical and clinical malaria and visceral leishmaniasis (VL) samples to generate unique data sets to identify novel immune molecules that can be targeted to improve human health. We have identified new clinical targets that can be directed for therapeutic advantage during infection, cancer and autoimmunity. We also investigate whether we can re-purpose existing drugs to target the molecules we have discovered, as well as generating and testing new therapeutics. We will identify drugs to improve disease outcomes in a broad range of inflammatory disease, as well as continue to test if these drugs can be employed to improve vaccines and/or drug treatment in malaria or leishmaniasis. We continue to collaborate with colleagues in disease endemic countries – most notably with researchers based at Banaras Hindu University in Varanasi, India and train students and postdoctoral fellows from these groups.
Discovery: LTα, and not TNF, is the principal mediator of experimental cerebral malaria: Engwerda, C. R., T. L. Mynott, S. Sawhney, J. B. De Souza, Q. Bickle and P. M. Kaye. Lymphotoxin-alpha, not Tumor Necrosis Factor-alpha, is the principle mediator in murine cerebral malaria. J Exp Med 2002, 195: 1371; cited 242 times
Discovery: critical roles for regulatory T (Treg) cells in malaria: Amante, F. H., A. C. Stanley, L. M. Randall, Y. Zhou, A. P. Waters, C. J. Janse, M. F. Good, G. R. Hill and C. R. Engwerda. A role for natural regulatory T cells in the pathogenesis of experimental cerebral malaria. Am J Path 2007, 171: 548
Discovery: how host immune factors allow malaria parasites to accumulate in tissues and cause disease:Amante, F. H., A. Haque, A. C. Stanley, F. Rivera, L. M. Randall, Y. A. Wilson, G. Yeo, C. Pieper, B. S. Crabb, T. F. de Koning-Ward, R. J. Lundie, M. F. Good, A. Pinzon-Charry, M. S. Pearson, M. G. Duke, D. P. McManus, A. Loukas, G. R. Hill and C. R. Engwerda. Immune-mediated mechanisms of parasite tissue sequestration during experimental cerebral malaria. J Immunol 2010, 185: 3632
Discovery: identified the molecular and cellular mechanisms by which type I interferons suppress anti-parasitic immunity: Haque, A., S. E. Best, M. Montes de Oca, K. R. James, A. Ammerdorffer, C. L. Edwards, F. de Labastida Rivera, F. H. Amante, P. T. Bunn, M. Sheel, I. Sebina, M. Koyama, A. Varelias, P. J. Hertzog, U. Kalinke, L. Rénia, C. Ruedl, K. P. A. MacDonald, G. R. Hill and C. R. Engwerda. 2014. Type I IFN signaling in CD8- DC’s impairs Th1-dependent malaria immunity. J Clin Invest 124:2483.
Identification: a major immunoregulatory pathway in malaria and leishmaniasis: Montes de Oca, M., R. Kumar, F. de Labastida Rivera, F. H. Amante, M. Sheel, R. J. Faleiro, P. T. Bunn, S. E. Best, L. Beattie, S. S. Ng, C. L. Edwards, W. Muller, E. Cretney, S. L. Nutt, M. J. Smyth, A. Haque, G. R. Hill, S. Sundar, A. Kallies and C. R. Engwerda. 2016. Blimp-1-dependent IL-10 production by Tr1 cells regulates TNF-mediated tissue pathology. PLoS Pathog 12: e1005398
Discovery: type I IFNs promote the development of above immunoregulatory pathways in humans: Montes de Oca, M., R. Kumar, F. L. Rivera, F. H. Amante, M. Sheel, R. J. Faleiro, P. T. Bunn, S. E. Best, L. Beattie, S. S. Ng, C. L. Edwards, G. M. Boyle, R. N. Price, N. M. Anstey, J. R. Loughland, J. Burel, D. L. Doolan, A. Haque, J. S. McCarthy and C. R. Engwerda. 2016. Type I interferons regulate immune responses in humans with blood-stage Plasmodium falciparum infection. Cell Rep 17: 399
Demonstration: type I IFNs can be modulated for therapeutic advantage in mice and humans: Kumar, R., P. T. Bunn, S. S. Singh, S. S. Ng, M. Montes de Oca, F. De Labastida Rivera, S. Bhushan Chauhan, N. Singh, R. J. Faleiro, C. L. Edwards, T. C. M. Frame, M. Sheel, R. J. Austin, S. W. Lane, T. Bald, M. J. Smyth, G. R. Hill, S. E. Best, A. Haque, D. Corvino, N. Waddell, L. Koufariotis, P. Mukhopadhay, M. Rai, J. Chakravarty, O. P. Singh, D. Sacks, S. Nylen, J. Uzonna, S. Sundar and C. R. Engwerda. 2020. Type I interferons suppress anti-parasitic immunity and can be targeted to improve treatment of visceral leishmaniasis. Cell Rep 30: 2512
Summary: major immunoregulatory pathways and their impact on disease outcome: Kumar, R., J. R. Loughland, S. S. Ng, M. J. Boyle and C. R. Engwerda. The regulation of CD4+ T cells during malaria. Immunol Rev 293: 70
Discovery: identifying NKG7 as a novel mediator of inflammation: Ng, S. S., F. de Labastida Rivera, J. Yan, D. Corvino, I. Das, P. Zhang, R. Kuns, S. B. Chauhan, J. Hou, X-Y Li, T. C. M. Frame, B. A. McEnroe, E. Moore, J. Na, J. A. Engel, M. S. F. Soon, B. Singh, A. J. Kueh, M. J. Herold, M. Montes de Oca, S. S. Singh, P. T. Bunn, A. R. Aguilera, M. Casey, M. Braun, N. Ghazanfari, S. Wani, Y. Wang, F. H. Amante, C. L. Edwards, A. Haque, W. C. Dougall, O. P. Singh, A. G. Baxter, M. W. L. Teng, A. Loukas, N. L. Daly, N. Cloonan, M. Degli-Esposti, J. Uzonna, W. R. Heath, T. Bald, S-K. Tey, K. Nakamura, G. R. Hill, R. Kumar, S. Sundar, M. J. Smyth and C. R. Engwerda. 2020. The Natural Killer cell granule protein NKG7 regulates cytotoxic granule exocytosis and inflammation. Nat Immunol In press
Discovery: from study with applications for a broad range of inflammatory diseases: Ng, S. S. and C. R. Engwerda. 2019. PCT/AU2019/050049. Modulating Immune Response
2019-current: Section Editor, PLoS Pathogens
2019-2020: Member, NHMRC Synergy Grant Assessment Panel
2016-2019: Associate Editor, PLoS Pathogens
2012-2015: Associate Editor, Journal of Immunology
2010-current: Member of the Specialist Editorial Board, International Journal for Parasitology
2007-current: Editorial Board, Infection and Immunity