21,111 Lakeshore Road
Ste Anne de Bellevue, QC
Canada H9X 3V9
petra [dot] rohrbach [at] mcgill [dot] ca (Email)
Malaria remains a leading cause of morbidity and mortality in the tropics and subtropics, being responsible for an estimated 500 million clinical cases and 1 million deaths annually. Options to control the spread of malaria are becoming increasingly limited since widely used antimalarials are losing their efficacy, including the 4-aminoquinoline drug chloroquine and the folate antagonists pyrimethamine and sulfadoxine. Moreover, reduced susceptibility has emerged to other antimalarials, including quinine, mefloquine, and possibly artemether.
In both microorganisms and tumours, drug resistance can arise from the presence of P-glycoproteins (P-gp) that are capable of extruding a broad range of structurally and functionally unrelated cytotoxic agents. P-gps belong to the ABC (ATP-binding cassette) transporter superfamily and are encoded by mdr genes. The human malaria parasite Plasmodium falciparum possesses an mdr homologue (pfmdr1) whose gene product, Pgh-1 (also known as PfMDR1), is expressed during intraerythrocytic development of the parasite. Pgh-1 is predominately located at the membrane of the parasite’s digestive vacuole. How polymorphisms within this transporter mediate anti-malarial drug responsiveness has remained obscure.
Using methods focused on live cell imaging and molecular biology, we aim to achieve a better understanding of the mechanisms involved in drug resistance in the intraerythrocytic stages of Plasmodium falciparum.
Dalton JP, Demanga CG, Reiling SJ, Wunderlich J, Eng JW, Rohrbach P.
Large-scale growth of the Plasmodium falciparum malaria parasite in a wave bioreactor. Int J Parasitol. 2012 Feb 8. [Epub ahead of print]
Guo Q, Reiling SJ, Rohrbach P, Ma H.
Microfluidic biomechanical assay for red blood cells parasitized by Plasmodium falciparum. Lab Chip. 2012 Mar 21;12(6):1143-50. Epub 2012 Feb 9.
Quantitative fluorescent live cell imaging of intracellular Ca2+ and H+ ions in malaria parasites. Methods Enzymol. 2012;505:469-83.
Rotmann A, Sanchez C, Guiguemde A, Rohrbach P, Dave A, Bakouh N, Planelles G, Lanzer M.
PfCHA is a mitochondrial divalent cation/H+ antiporter in Plasmodium falciparum. Mol Microbiol. 2010 Jun;76(6):1591-606. Epub 2010 May 4.
Oster N, Rohrbach P, Sanchez CP, Andrews KT, Kammer J, Coulibaly B, Stieglbauer G, Becher H, Lanzer M.
Apparent bias for P. falciparum parasites carrying the wild-type pfcrt allele in the placenta. Parasitol Res. 2010 Apr;106(5):1065-70. Epub 2010 Feb 11.
Koncarevic S, Rohrbach P, Deponte M, Krohne G, Prieto JH, Yates J 3rd, Rahlfs S, Becker K.
The malarial parasite Plasmodium falciparum imports the human protein peroxiredoxin 2 for peroxide detoxification. Proc Natl Acad Sci U S A. 2009 Aug 11;106(32):13323-8. Epub 2009 Aug 3.
Imaging ion flux and ion homeostasis in blood stage malaria parasites. Biotechnol J. 2009 Jun;4(6):812-25. Review.