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Hangjun Ke

Hangjun Ke, PhD

Assistant Professor


Department: Microbiology & Immunology

Education

  • Bachelor of Medicine – Tongji Medical College of Huazhong University of Science and Technology, China (2002)
  • MS in Immunology – Tongji Medical College of Huazhong University of Science and Technology, China (2005)
  • PhD in Parasitology – Drexel University College of Medicine (2011)
Hangjun Ke, PhD, is an assistant professor in the Department of Microbiology & Immunology at Drexel University College of Medicine.

Research Overview

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

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

Research Interests

Development of novel antimalarial drugs that can overcome the drug-resistance problems of antimalarial chemotherapy

Research

The tubular mitochondrion of a malaria parasite
The tubular mitochondrion of a malaria parasite

Mitochondria trace their origin from the symbiotic union of an alpha-proteobacterium and an ancient archaeon or proto-eukaryote. From this single symbiotic event, and over millions of years under varied evolutionary forces, the mitochondrion has evolved a tremendous diversity of structures and functions among the multitude of extant eukaryotes. This diversity allows eukaryotic organisms to occupy wide-ranging and diverse environmental niches on the planet. Nearly all eukaryotes have mitochondria or derived organelles, relying on mitochondria for energy, metabolites, essential cofactors and/or signaling, including regulation of cellular life and death. The phylum Apicomplexa comprises a vast group of single-celled protists, including many medically important parasites that can cause diseases like malaria, toxoplasmosis, cryptosporidiosis, babesiosis, cyclosporiasis and isosporiasis. The mitochondria of pathogenic protists are very divergent from the counterparts of humans, which would provide a foundation of selective toxicity that facilitates drug development.

Primary interest: The current main research focus of the lab is the mitochondrial ribosomes (mitoribosomes) of malaria parasites. The mitochondrion in malaria parasites is an important antimalarial drug target. During the intraerythrocytic developmental cycle, a single mitochondrion elongates, branches and equally disseminates into progeny merozoites. There are around 250 genes that are encoded in the nucleus (5% of the nuclear genome) and targeted to this organelle, but just three genes encoded by the mitochondrial genome.

The 6 kb mitochondrial DNA of malaria parasites is the smallest mitochondrial genome in the entire eukaryotic kingdom, only encoding cytochrome b and cytochrome c oxidase subunits I and III. These three proteins are key components of the mitochondrial electron transport chain (mtETC), which is absolutely essential for the parasite. In asexual blood stages, the mtETC is mainly required to reoxidize ubiquinol to ubiquinone, which is needed for the activity of dihydroorotate dehydrogenase (DHODH), an essential enzyme of the pyrimidine biosynthesis pathway.

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.

Publications

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


Contact Information


Research Office

Department of Microbiology & Immunology
2900 W. Queen Lane
Philadelphia, PA 19129

Room: G39
Phone: 215.991.8448
Fax: 215.848.2271