Faculty Profile : Department of Biology : Indiana University Bloomington

Faculty & Research

Faculty Profile

Ke Hu

Research Images

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) (The mitochondrion is not included in the drawing).

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).

Assistant Professor of Biology

IU Affiliations
Biocomplexity Institute

Contact Information: Contact Ke Hu by kehu [at] indiana [dot] edu; By telephone: 812-855-0166/5-0311(lab); MY 216A / MY 230 (lab)

Program

Molecular, Cellular & 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
Scripps Research Institute, 2003-2006
Awards: Beckman Young Investigator Award, 2008
Basil O\'Connor Starter Scholar Research Award, 2010

Research Description

Our lab is interested in understanding how cytoskeletal structures are organized and function in a group of fascinating eukaryotic parasites, the Apicomplexans. The phylum Apicomplexa contains ~ 5,000 species of obligate intracellular protozoan parasites, many of which are important human or animal pathogens, including Plasmodium falciparum, the most lethal cause of malaria that kills more than a million people every year, and Toxoplasma gondii, the leading cause of congenital neurological defects in humans and a devastating opportunistic infection in immunocompromised patients.

The pathogenesis of these diseases is directly related to parasite replication, the understanding of which is thus crucial for developing effective therapies. The replication of apicomplexan parasites is based upon the formation of daughter cytoskeletal scaffolds within the mother cell, which provide the framework for organellar replication and partition and are essential for parasite survival, therefore are attractive potential drug targets (Fig. 1). In addition, the cytoskeletal scaffolds of these parasites are spectacular structures (Fig. 2), the biogenesis of which poses questions that are of general interest for cell biology (Fig. 3).

The apicomplexan cytoskeletons are highly polarized and the body plan for assembly increasingly seems to be based on compartmentation along the apical-basal axis. The long term goal of our lab is to understand the origination, compartmentation and maturation of cytoskeletal scaffolds in the apicomplexan parasites using advanced light and electron microscopy, molecular biology, and proteomics techniques. Our study will mainly focus on the cytoskeletal biogenesis of Toxoplasma gondii, because of its greater suitability for biochemical, light and electron microscopy investigation. In particular, we seek to answer the following questions:

What are the very early processes that template the final structure of the Apicomplexan cytoskeletal scaffold, determine its striking polarity, and might provide clinically relevant targets for disruption of parasite replication?
When and where do these early steps occur?
What is the underlying molecular machinery that defines the structure and regulates the construction process?

Answers to these questions will have important implications for general understanding of how specialized regions can be demarcated and assembled in highly polarized cells, for the biogenesis of the cytoskeleton of this group of important human pathogens, and consequently for the rational selection of chemotherapeutic targets for improved control of the Apicomplexan diseases.

Select Publications

Senthilkumar Sivagurunathan, Aoife Heaslip, Jun Liu, Ke Hu. 2013. "Identification of functional modules of AKMT, a novel lysine methyltransferase regulating the motility of Toxoplasma gondii" Molecular & Biochemical Parasitology In Press

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, Accepted

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 gondii. PLoS Pathogens 6(2):e1000754

A. T. Heaslip, S. C. Ems-McClung, K. Hu 2009. "TgICMAP1 is a novel microtubule binding protein in Toxoplasma gondii. PLoS 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., 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.

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.

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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