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- Rachel Zufferey
Leishmania species and Trypanosomes are arthropod-born protozoan parasites that cause important diseases in human and animals, and affect tenths of million patients worldwide. Because of the lack of effective vaccine and adequate pharmacological agents, more efficacious drugs are urgently needed for treatment of these debilitating diseases. Glycerolipid biosynthesis is essential for the generation of cellular membranes and cell surface glycerolipid-based virulence factors that play crucial roles for establishment of a successful infection in the vertebrate host. The goal of our research is to understand how the parasites generate their membranes, how this process affects their virulence, and understand the mechanism of action of lipid-based drugs, some of which are in clinical trials. The focus of our research is to characterize enzymes involved in the biosynthesis of various classes of glycerolipids with an eye toward drug and vaccine development. We employ a combination of genetic, molecular and cell biology, and biochemical approaches to assess the roles of these enzymes in the biosynthesis of lipids and lipid-based virulence factors, and in virulence. Last, we are also interested in understanding the process of mitochondrial fission during cytokinesis in Leishmania.
Our work has been carried out by numerous graduate and undergraduates students who further their education at prestigious schools such as Columbia University, University of Connecticut Health Center, Kansas City Medical School, University of Michigan, and University of Kansas. Our research has also been enhanced by collaborations with colleagues from Brown University, Iowa State University, and Kansas State University.
Our research has been funded by the American Heart Association, the National Institute of Health, and by various private organizations.
- BIO2000: Introduction in Molecular and Cell Biology
- BIO2280: General Microbiology
- Zufferey, R. and Ben Mamoun, C.; Choline transport in Leishmania major promastigotes and its inhibition by choline and phosphocholine analogs. Mol. Biochem. Parasitol. 125: 127-134, 2002.
- Zufferey, R., Allen, S., Barron, T., Sullivan, D.R., Denny, P.W., Almeida, I.C., Smith, D.F., Turco, S.J., Ferguson, M.A.J. and Beverley, S.M.; Etherphospholipids and glycosylinositolphospholipids (GIPLs) are not required for amastigote virulence nor for inhibition of macrophage activation by Leishmania major. J. Biol. Chem. 278(45): 44708-18, 2003.
- Zufferey, R., Santiago, S., Brachet, V. and Ben Mamoun, C.; Reexamining the role of choline transporter-like (Ctlp) proteins in choline transport. Neurochem. Res. 29(2), 461-467, 2004.
- Roggero, R., Zufferey, R., Minca, M., Richier, E., Calas, M., Vial, H. and Ben Mamoun, C.; Unraveling the mode of action of the anti-malarial choline analog G25 in yeast. Antimicrob. Agents Chemother. 48 (8):2816-24, 2004.
- Zufferey, R. and Ben Mamoun, C.; The initial step of glycerolipid metabolism in Leishmania major promastigotes involves a single glycerol-3-phosphate acyltransferase enzyme important for the synthesis of triacylglycerol but not essential for virulence. Mol. Microbiol. 56(3):800-10, 2005.
- Zufferey, R. and Ben Mamoun, C.; Leishmania major expresses a single dihydroxyacetonephosphat acyltransferase localized in the glycosome, important for rapid growth and essential for survival at high cell density. J. Biol. Chem. 281(12):7952-9, 2006.
- ElBissati, K., Zufferey, R., Witola, W., Carter, N., Ullman, B. and Ben Mamoun, C.; The plasma membrane permease PfNT1 is essential for purine salvage in the human malaria parasite Plasmodium falciparum. Proc. Natl. Acad. Sci. U.S.A., 103(24):9286-91, 2006.
- Zufferey, R., Al-Ani, G.K., and Dunlap, K.; Leishmaniadihydroxyacetonephosphate acyltransferase LmDAT is important for ether lipid biosynthesis but not for the integrity of detergent resistant membranes. Molec. Biochem. Parasitol. 168, 177-85, 2009.
- Downie, M.J, El Bissati, K., Bobenchik, A.M., Nic Lochlainn, L., Amerik, A., Zufferey, R., Kirk, K. and Ben Mamoun, C.; PfNT2: a permease of the equilibrative nucleoside transporter family in the endoplasmic reticulum of Plasmodium falciparum. J. Biol. Chem. 285(27):20827-33, 2010.
- Al-Ani, G.K., Patel, N., Pirani, K.A., Zhu, T., Dhalladoo, S., Zufferey, R.; The N-terminal domain and glycosomal localization of Leishmania initial acyltransferase LmDAT are important for lipophosphoglycan synthesis. PLoS One 6(11):e27802, 2011.
- Zufferey, R., Bibis, S.S., Zhu, T., and Dhalladoo, S.; Characterization of a compensatory mutant of Leishmania major that lacks ether lipids but exhibits normal growth, and G418 and hygromycin resistance; Exp Parasitol. 130(3):200-4. 2012.
- Bibis, S.S., Dahlstrom, K., Zhu, T., and Zufferey, R.; Characterization of Leishmania major phosphatidylethanolamine methyltransferases LmjPEM1 and LmjPEM2 and their inhibition by choline analogs; Molec. Biochem. Parasitol. 2014, under revision