Dr. Ke’s lab is mainly interested in the mitochondria of protozoans, including malaria parasites. The overall goal is to characterize essential pathways of the parasite for developing novel antimalarial drugs.

The intraerythrocytic developmental cycle of Plasmodium falciparum, from L-R: merozoite, ring, trophozoite and schizont

Graduate student: Swati Dass
Postdoctoral researcher: Maruthi Mulaka, PhD

Recent studies have suggested that, in the mosquito stages, the mtETC is also important for the generation of mitochondrial membrane potential (∆ψm) to power oxidative phosphorylation for ATP generation. The bc₁ complex of mtETC is a major antimalarial drug target, as demonstrated by various research groups over the years; however, we remain largely ignorant of the structure and function of the mitoribosome that translates the critical mtETC components. Although direct evidence for mitochondrial translation in malaria parasites (or in the phylum Apicomplexa) has been lacking, the essentiality of mtETC and appearance of cytochrome b mutations conferring atovaquone resistance imply that the mitochondrial ribosome is active. The deep divergence of the malarial mitoribosome from the human counterpart may also provide a basis for development of highly selective antimalarial chemotherapies. The overall goal of this project is to identify the specific components of the malarial mitoribosomes and to decipher their structures.

Secondary interest: We are also very interested in the mitochondria of Tetrahymena, a ciliate that is related to Apicomplexa. Tetrahymena and Apicomplexa are members of the Alveolate group.

Published Full-length Papers
(*corresponding author)

"The mitochondrial ribosomal protein L13 is critical for the structural and functional integrity of the mitochondrion in Plasmodium falciparum"
*Ke H, Dass S, Morrisey JM, Mather MW, Vaidya AB
J Biol Chem. pii: jbc.RA118.002552. doi: 10.1074/jbc.RA118.002552. [Epub ahead of print], April 6, 2018

"Targeting mitochondrial functions as antimalarial regime, what is next? Current Clinical Microbiology Reports"
*Ke H, Mather MW
Curr Clin Micro Rpt 4:175–191, March 2017

"Caged Garcinia Xanthones, a novel chemical scaffold with potent antimalarial activity"
*Ke H, Morrisey JM, Qu S, Chantarasriwong O, Mather MW, Theodorakis EA, Vaidya AB
Antimicrob Agents Chemother.; 61(1), Dec 27, 2016

"Genetic investigation of tricarboxylic acid metabolism during the Plasmodium falciparum life cycle"
Ke H, Lewis IA, Morrisey JM, McLean KJ, Ganesan SM, Painter HJ, Mather MW, Jacobs-Lorena M, Llinás M, Vaidya AB
Cell Rep.;11(1):164-74, Apr 7, 2015

"The heme biosynthesis pathway is essential for Plasmodium falciparum development in mosquito stage but not in blood stages"
Ke H, Sigala PA, Miura K, Morrisey JM, Mather MW, Crowley JR, Henderson JP, Goldberg DE, Long CA, Vaidya AB
J Biol Chem.; 289(50):34827-37, Dec 12, 2014

"The antimalarial activities of methylene blue and the 1,4-naphthoquinone 3-[4-(trifluoromethyl)benzyl]-menadione are not due to inhibition of the mitochondrial electron transport chain"
Ehrhardt K, Davioud-Charvet E, Ke H, Vaidya AB, Lanzer M, Deponte M
Antimicrob Agents Chemother.; 57(5):2114-20, May 2013

"Mitochondrial RNA polymerase is an essential enzyme in erythrocytic stages of Plasmodium falciparum"
Ke H, Morrisey JM, Ganesan SM, Mather MW, Vaidya AB
Mol Biochem Parasitol.; 185(1):48-51, Sep 2012

"ATP synthase complex of Plasmodium falciparum: dimeric assembly in mitochondrial membranes and resistance to genetic disruption"
Balabaskaran Nina P, Morrisey JM, Ganesan SM, Ke H, Pershing AM, Mather MW, Vaidya AB
J Biol Chem.; 286(48):41312-22, Dec 2, 2011

"A chemical genomic analysis of decoquinate, a Plasmodium falciparum cytochrome b inhibitor"
McCormack S, Bursulaya B, Ke H, Vaidya AB, Schultz PG, Winzeler EA
ACS Chem Biol.; 6(11):1214-22, Nov 18, 2011

"Variation among Plasmodium falciparum strains in their reliance on mitochondrial electron transport chain function"
Ke H, Morrisey JM, Ganesan SM, Painter HJ, Mather MW, Vaidya AB
Eukaryot Cell.; 10(8):1053-61, Aug 2011

"Yeast dihydroorotate dehydrogenase as a new selectable marker for Plasmodium falciparum transfection"
Ganesan SM, Morrisey JM, Ke H, Painter HJ, Laroiya K, Phillips MA, Rathod PK, Mather MW, Vaidya AB
Mol Biochem Parasitol.; 177(1):29-34, May 2011