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Indiana University Bloomington

Department of Biology

Faculty & Research

Faculty Profile

Ke Hu

Photo of Ke Hu
Research Images
Research photo by Ke Hu

Figure 1. Cell division in Apicomplexan parasites.  Apicomplexan parasites prepare for division by forming daughter cytoskeleton scaffolds within the mother. The de novo constructed daughter cytoskeletons (green) serve as scaffolds for organelle biogenesis and partitioning, while the mother cytoskeleton (red) remains intact for most of cell cycle.  The apicomplexan parasites differ in the number of daughters formed at each cell cycle, which varies from 2 (e.g. T. gondii as illustrated) to 2n (n>1) (e.g. P. falciparum).

Research photo by Ke Hu

Figure 2. Drawings of T. gondii.  left: a longitudinal section of a dividing cell. Lobes of the dividing nucleus bordered by ER, Golgi (yellow)  are surrounded by the developing daughters' scaffolds (red).  Maternal and daughter conoids are shown in green, secretory organelles (rhoptries) in purple.  T. gondii has three membranes: a plasma membrane (black) and two additional layers (IMC, red) formed from a patchwork of flattened vesicles. middle:  semi-transparent view showing the 22 subpellicular MT (green) right: Enlarged view of the apical complex cytoskeleton, showing the conoid (green), preconoidal and polar rings (brown) and two intra-conoid MT (green).  The conoid is formed of 14 fibers of tubulin (not MT), 430 nm long, arranged in a left-handed spiral (Hu et al., JCB 2002).

Associate Professor of Biology

IU Affiliations
Biocomplexity Institute

Contact Information
By telephone: 812-855-0166/5-0311(lab)
MY 216A / MY 230 (lab)


Program
Genome, Cell & Developmental Biology
Research Areas
  • Eukaryotic Cell Biology, Cytoskeleton and Signaling
  • Microbial Cell Biology and Environmental Responses
  • Microbial Interactions and Pathogenesis
Education

Ph.D., University of Pennsylvania, 2002
Postdoctoral Fellow, University of Pennsylvania, 2002-2003
Postdoctoral Fellow, The Scripps Research Institute, 2003-2006

Awards

Beckman Young Investigator Award, 2008

Basil O'Connor Starter Scholar Research Award, 2010

Research Description

Toxoplasma gondii is one of the most successful parasites on earth, permanently infecting nearly 20% of the global population.  Infections in immunocompromised individuals and the unprotected fetus have devastating consequences, including the development of lethal Toxoplasma encephalitis.  Besides being an important human parasite itself, T. gondii is a model for its ~6000 relatives in the Phylum Apicomplexa, including the malaria parasites.  

Although toxoplasmosis is a very severe disease, its pathogenesis is simple: tissue destruction by reiteration of the parasite’s lytic cycle of host cell invasion, parasite replication, and egress.  The parasite’s cytoskeleton (literally, the "skeleton" of a cell), formed of several distinct types of biopolymers, is required for every step in this cycle.  It drives motility for invasion and egress, provides strength for the cortex (for withstanding the extreme deformation the parasite experiences as it moves in and out of the host cell), and provides the framework for the unusual “born-within” type of parasite replication (Fig 1 & 2).  The “life-style” of this extraordinarily successful parasite therefore depends on a specialized and unusual set of cytoskeletal properties. 

My group focuses on understanding the construction and function of the structural framework of this invasion machine.  We take advantage of the highly ordered cytoskeletal architecture and streamlined motility of T. gondii to uncover fundamental principles for structural inheritance and force transmission.  At the same time, we combine the investigation of basic processes with the discovery of novel drug targets for T. gondii and malaria parasites.  Specific questions include:  How does a cell reproducibly establish its characteristic cellular architecture? How does the cytoskeleton control the shape, mechanical strength, and biogenesis of the cellular cortex? How do internal and external signals regulate force generation to drive directional cellular movement?  We combine molecular genetics, proteomics, super-resolution imaging and biophysical techniques to answer these questions. 

Select Publications
Jun Liu, Laura Wetzel, Ying Zhang, Eiji Nagayasu, Stephanie Ems-McClung, Laurence Florens, Ke Hu.  2013. "Novel thioredoxin-like proteins are components of a protein complex coating the cortical microtubules of Toxoplasma gondii" Eukaryotic Cell 12(12):1588-99 (Featured on cover of journal)
Senthilkumar Sivagurunathan, Aoife Heaslip, Jun Liu, Ke Hu. 2013. "Identification of functional modules of AKMT, a novel lysine methyltransferase regulating the motility of Toxoplasma gondiiMolecular & Biochemical Parasitology 189: 43–53.
A.T. Heaslip, M. Nishi, B. Stein, K. Hu 2011. The motility of a human protozoan parasite, Toxoplasma gondii, is regulated by a novel lysine methyltransferase. PLoS Pathogens 7(9): e1002201 (Faculty of 1000 Selection)
A.T. Heaslip, F. Dzierszinski, B. Stein,  K. Hu 2010.  TgMORN1 is a key organizer of the basal complex in Toxoplasma gondiiPLoS Pathogens 6(2):e1000754
A. T. Heaslip, S. C. Ems-McClung, K. Hu 2009. "TgICMAP1 is a novel microtubule binding protein in Toxoplasma gondiiPLoS One 4(10): e7406. doi:10.1371/journal.pone.0007406
Hu K 2008. "Organizational changes of the daughter basal complex during the parasite replication of Toxoplasma gondii.". PLoS Pathogens 4(1): e10 doi:10.1371/journal.ppat.0040010
Manami Nishi, Ke Hu, John M. Murray, and David S. Roos 2008. “How to Build a Parasite: Organellar Dynamics during the Cell Cycle of Toxoplasma gondii”.  Journal of Cell Science 121:1559-1568
Natalia de Miguel, Maryse Lebrun, Aoife Heaslip, Ke Hu, Con J. Beckers, Mariana Matrajt, Jean François Dubremetz and Sergio O. Angel  2008. Toxoplasma gondii Hsp20 is a stripe-arranged chaperone localized in the outer leaflet of the inner membrane complex. Biology of the Cell 100(8):479-89
Hu, K*., Ji L*., Applegate, K.T., Danuser G., Waterman-Storer C. 2007. "Differential Transmission of Actin Motion Within Focal Adhesions." Science 315:111-115. (Featured in "Editor's Choice" in Science: S. M. Hurtley, Cellular Mechanics Up Close and Personal. Sci. STKE 2007, tw15 (2007))(Faculty of 1000 Selection)
K. Hu, J. Johnson, L. Florens, M. Fraunholz, S. Suravajjala, C. DiLullo, J. Yates, D. S. Roos and J. M. Murray   2006.”Cytoskeletal components of an invasion machine – the apical complex of Toxoplasma gondii” (cover) PloS Pathogens, 2(2): 0121-0138 (Faculty of 1000 Selection)
Stacey D. Gilk, Yossef Raviv, Ke Hu, John Murray, Con J.M. Beckers, and Gary E. Ward 2006.
“Identification of PhIL1, a Novel Cytoskeletal Protein of the Toxoplasma gondii Pellicle, through Photosensitized Labeling with 5-[125I]Iodonaphthalene-1-Azide”. Eukaryotic Cell  5: 1611-1621
K. Hu, D. S. Roos, S. O. Angel and J. M. Murray  2004. “Variability and heritability of cell division pathways in T. gondii” Journal of Cell Science  2004 117: 5697-5705
D. M. Wetzel, S. Hakansson, K. Hu, D. Roos, and L. D. Sibley  2003.  “Actin Filament Polymerization Propels Gliding Motility by Apicomplexan Parasites” Molec. Biol. Cell  14: 396-406
Hu, K., T. Mann, B. Striepen, C.J. M. Beckers, D. S. Roos and J. M. Murray. 2002. “Daughter cell assembly in the protozoan parasite Toxoplasma gondii”  Molec. Biol. Cell 13: 593-606.
Hu, K., D. S. Roos and J. M. Murray.  2002.  “A novel polymer of tubulin forms the conoid in Toxoplasma gondii”(cover)  J. Cell Biol. 156:1039-1050.
Swedlow, J.R., K. Hu, P.D. Andrews, D. S. Roos and J. M. Murray.  2002. “Measurement of tubulin content in the conoid and spindle pole of the parasite Toxoplasma gondii: A comparison of laser scanning confocal and wide field fluorescence microscopy for quantitative analysis in living cells” Proc. Nat'l Acad. Sci. USA 99:2014-2019.
Pelletier, L., Stern, A., Pypaert, M., Sheff, D., Ngo, H., Roper, N., He, C., Hu, K., Toomre, D., Coppens, I., Roos, D., Joiner, K and Warren, G 2002. "Golgi Biogenesis in Toxoplasma gondii."  Nature  418, 548-552.

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