Professor

BS, Microbiology and Biology, University of Michigan
PhD, Microbiology, Michigan State University
ACS Postdoctoral Fellow, UCLA
NSF Postdoctoral Fellow, U. Wisc.
Visiting scientist, GlaxoSmithKline, Johnson & Johnson

Program Affiliation: Molecular Biology & Genetics | Microbiology

Research Groups Affiliation: Biochemistry | Cell Biology | Microbiology | Plant Sciences

Email Cheng

The Kao lab and families will be moving from College Station to Bloomington by the end of 2008.

We are interested in both basic and applied studies of how RNA viruses interact with the host cell. The lab has three interrelated areas of focus, and these have the potential to enrich each other. The three areas are:

1. RNA virus replication. We study three viruses with positive-strand RNA genomes (positive-strand RNAs are functionally equivalent to mRNAs): Hepatitis C Virus, the SARS coronavirus, and the plant-infecting Brome Mosaic Virus. We are especially interested in the enzymes for viral RNA synthesis, such as RNA-dependent RNA polymerases. We also study the communication and crosstalk between different viral processes (replication, translation, encapsidation, etc.).

2. Innate immunity receptors. These receptors recognize and initiate the responses that can limit or stop pathogen infections. We are interested in the structure and function of the receptors that recognize viral RNA ligands, such as Toll-Like Receptor 3, and RIG-I and we want to elucidate to develop reagents to regulate their activities. We are also studying how different receptors communicate with each other in response to pathogen infections.

3. Viral Nanotechnology. Viral capsids have the amazing ability to assemble into virus-like particles even in the absence of other proteins. We are interested in using these properties as well as the ability to genetically engineer the capsids to make novel imaging tools and delivery vectors.

The HCV RNA-dependent RNA polymerase can open and close the template channel to allow it to accommodate both the template and nascent RNA during RNA synthesis.	Viral capsids can package novel and useful materials. The top two images show electron micrographs of native particles from Brome Mosaic Virus (BMV) at two magnifications. The bottom two images show reassembled BMV-like particles containing nanogold particles. Note that these particles are sufficiently homogeneous to form crystal lattices.	The structure of the SARS virus endoribonuclease. The structure was derived from X-ray crystallography and shows the unusual hexameric structure of the enzyme. The active sites of the subunits, where seen, are highlighted in yellow. In addition to serving as an RNA processing enzyme, this protein can perturb normal regulation of the cell cycle.	A model of the innate immunity receptor, Toll-like Receptor 3 (TLR3). TLR3 is one of the early sentries for vertebrate cells to detect invasion by RNA viruses. The molecule binds to RNA as a dimer to send a signal through the alpha-helical transmembrane domain to activate kinases that will perpetuate and amplify the signal that leads to cytokine production.

Bhardwaj, K., S. Palaninathan, L. Yi. L. Guarino, J. Sacchettini, and C. Kao. 2008. Structure, function, and substrate specificity for the SARS-CoV Nsp15 endoribonuclease. J. Biol. Chem. 283, 3655-3664.

Yi, G. and C. Kao. 2008. Cis- and trans-acting functions of brome mosaic virus protein 1a in genomic RNA1 replication. J. Virol. 82, 3045-3053.

Gangloff, M., A. Murali, J. Xiong, C. J. Arnot, A.N. Weber, A. M. Sandercock, C.V. Robinson, R. T. Sarisky, A. Holzenburg. N. J. Gay* and C. Kao* (Co-corresponding authors). 2008. An indirect alosteric mechanism for activation of the Toll receptor by the dimeric ligand Spatzle. J. Biol. Chem. 283, 14629-14635.

Ranjith-Kumar, C.T. K.E. Duffy, J.L. Jordan, A. Eaton-Bassiri, R.T. Sarisky, and C. Kao. 2008. Single-stranded deoxyoligonucleotides are potent inhibitors of cytokine production induced by the human Toll-Like Receptor 3. Mol. Cell. Biol. 28, 4507-4519.

Murali, A., X. Li, C.T. Ranjith-Kumar, K. Bhardwaj, A. Holzenburg, P. Li, and C. Kao. 2008. Structure and function of LGP2, a DExD/H helicase that regulates the innate immunity response. J. Biol. Chem. 283:15825-15833.

Chinnaswamy S., I. Yarbrough, S. Palaninathan, C. T. Ranjith Kumar, V. Vijayaraghavan, B. Demeler, S.M. Lemon3, J. C. Sacchettini, and C. C. Kao. 2008. A locking mechanism regulates RNA synthesis and host protein interaction by the hepatitis C virus polymerase. J. Biol. Chem. 283(29):20535-20536. Doi:10.1074/jbc.M801490200.

Gopinath, K., and C. Kao. 2007. Reconstitution of viral RNA infection through trafficking of viral RNAs in plants. The Plant Cell 19, 1-13. Sun, J., DuFort, C. A. Murali, M. D. Daniel, C. Chen, K. Gopinath, B. Stein, M. De, Vince Rotello, A. Holzenburg, C. C. Kao, and B. Dragnea. 2007. Core-controlled polymorphism in virus-like particles. Proc. Natl. Acad. Sci. USA 104:1354-1359.

Zhu, J., K. Gopinath, G. Yi, D. Hayward, H, Zhu, and C. Kao. 2007. RNA-binding Proteins that Inhibit RNA Virus Infection. Proc. Natl. Acad. Sci. USA 104: 3129-9134.

Yi, G. and C. Kao. 2007. Selective repression of translation by the Brome Mosaic Virus 1a RNA replication protein. J. Virol. 81: 1601-1609.