Our laboratory works on a variety of eukaryotic parasitic organisms of global health importance. These range from single cell protozoa like trypanosomes and Leishmania, to multicellular helminth parasites like schistosome blood flukes. Our primary interest is in the molecular mechanisms by which parasites invade their host, acquire nutrients from the bloodstream, and evade the host immune response. We use a broad array of research tools ranging from gene deletion and RNAi technologies, to confocal imaging and protein structure determination. One major focus is on the role of proteases in the life cycle of parasites and the diseases they produce. A tangent to our work is the development of new drugs for human parasitic diseases in collaboration with other laboratories in the Sandler Center at Mission Bay.
Ingram JR, Rafi SB, Eroy-Reveles AA, Ray M, Lambeth L, Hsieh I, Ruelas D, Lim KC, Sakanari J, Craik CS, Jacobson MP, McKerrow JH. Investigation of the Proteolytic Functions of an Expanded Cercarial Elastase Gene Family in Schistosoma mansoni. PLoS Negl Trop Dis. 2012 Apr;6(4):e1589. Epub 2012 Apr 3.
Quezada LA, Sajid M, Lim KC, McKerrow JH.A blood fluke serine protease inhibitor regulates an endogenous larval elastase. J Biol Chem. 2012 Mar 2;287(10):7074-83. Epub 2011 Dec 15.
Doyle PS, Zhou YM, Hsieh I, Greenbaum DC, McKerrow JH, Engel JC.The Trypanosoma cruzi protease cruzain mediates immune evasion. PLoS Pathog. 2011 Sep;7(9):e1002139. Epub 2011 Sep 1.
Jílková A, Rezácová P, Lepsík M, Horn M, Váchová J, Fanfrlík J, Brynda J, McKerrow JH, Caffrey CR, Mares M. Structural basis for inhibition of cathepsin B drug target from the human blood fluke, Schistosoma mansoni. J Biol Chem. 2011 Oct 14;286(41):35770-81. Epub 2011 Aug 10.
De Muylder G, Ang KK, Chen S, Arkin MR, Engel JC, McKerrow JH. A screen against Leishmania intracellular amastigotes: comparison to a promastigote screen and identification of a host cell-specific hit. PLoS Negl Trop Dis. 2011 Jul;5(7):e1253. Epub 2011 Jul 19.
Mackey ZB, Koupparis K, Nishino M, McKerrow JH. High-throughput analysis of an RNAi library identifies novel kinase targets in Trypanosoma brucei. Chem Biol Drug Des. 2011 Sep;78(3):454-63. doi: 10.1111/j.1747-0285.2011.01156.x. Epub 2011 Jul 14.
Sajid M, Robertson SA, Brinen LS, McKerrow JH. Cruzain: the path from target validation to the clinic. Adv Exp Med Biol. 2011;712:100-15. Review.