Infectious Diseases and Immunology
2705, boulevard Laurier, RC-709
CANADA G1V 4G2
Malaria is one of the world’s most common infectious diseases, with approximately 500 million cases each year and 2 million deaths, and thus represents one of the most devastating global public health problems. The lack of an effective vaccine, the emergence of resistance to first-line drugs like chloroquine and antifolates and recent reports of clinical cases of reduced susceptibility to artemisinine in Cambodia, combined with the small number of suitable new drugs against the malaria parasite demonstrate the urgent need for the development and implementation of novel intervention strategies in the form of drugs, vector control measures and an effective vaccine. Indeed, it is expected that if the trend in malaria prevalence stays on its current upwards course, the death rate could double in the next twenty years.
Invasion of a red blood cell by Plasmodium falciparum merozoites is an essential step in the malaria lifecycle and host response to merozoite antigens are an important component of human malarial immunity. Consequently, the molecular players involved in erythrocyte invasion are key targets for both therapeutic and vaccine-based strategies to block parasite development. Several of these invasion proteins are stored in the apical complex of the merozoite, a structure containing secretory organelles called dense granules, micronemes and rhoptries, and are released at different times during invasion. Because of its essential role, interfering with the generation of the apical complex represents a very attractive target for the design of a new kind of antimalarial. Our studies will
focus on trying to understand how the parasite directs proteins to the different structures of the apical complex. Understanding this complex process will likely provide a wealth of new targets for the development of strategies to block apical complex generation and preventing malaria pathogenesis.
Andreani G, Lodge R, Richard D, Tremblay MJ.
Mechanisms of interaction between protozoan parasites and HIV. Curr Opin HIV AIDS. 2012 Mar 13. [Epub ahead of print]
Chen L, Lopaticki S, Riglar DT, Dekiwadia C, Uboldi AD, Tham WH, O'Neill MT, Richard D, Baum J, Ralph SA, Cowman AF.
An EGF-like protein forms a complex with PfRh5 and is required for invasion of human erythrocytes by Plasmodium falciparum. PLoS Pathog. 2011 Sep;7(9):e1002199. Epub 2011 Sep 1.
Richard D, Bartfai R, Volz J, Ralph SA, Muller S, Stunnenberg HG, Cowman AF.
A genome-wide chromatin-associated nuclear peroxiredoxin from the malaria parasite Plasmodium falciparum. J Biol Chem. 2011 Apr 1;286(13):11746-55. Epub 2011 Jan 31.
Riglar DT, Richard D, Wilson DW, Boyle MJ, Dekiwadia C, Turnbull L, Angrisano F, Marapana DS, Rogers KL, Whitchurch CB, Beeson JG, Cowman AF, Ralph SA, Baum J.
Super-resolution dissection of coordinated events during malaria parasite invasion of the human erythrocyte. Cell Host Microbe. 2011 Jan 20;9(1):9-20.
Tham WH, Wilson DW, Lopaticki S, Schmidt CQ, Tetteh-Quarcoo PB, Barlow PN, Richard D, Corbin JE, Beeson JG, Cowman AF.
Complement receptor 1 is the host erythrocyte receptor for Plasmodium falciparum PfRh4 invasion ligand. Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17327-32. Epub 2010 Sep 20.
O'Neill MT, Phuong T, Healer J, Richard D, Cowman AF.
Gene deletion from Plasmodium falciparum using FLP and Cre recombinases: implications for applied site-specific recombination. Int J Parasitol. 2011 Jan;41(1):117-23. Epub 2010 Sep 17.
Richard D, MacRaild CA, Riglar DT, Chan JA, Foley M, Baum J, Ralph SA, Norton RS, Cowman AF.
Interaction between Plasmodium falciparum apical membrane antigen 1 and the rhoptry neck protein complex defines a key step in the erythrocyte invasion process of malaria parasites. J Biol Chem. 2010 May 7;285(19):14815-22. Epub 2010 Mar 12.