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Hu, Ronggui
Professor
Institute of Biochemistry and Cell Biology
86-21-54921408
coryhu@sibs.ac.cn
http://www.sibcb.ac.cn/ePI.asp?id=129

Research Focus

Our lab is committed to research into fundamental biological problems and disease pathology. We focus on the following different but intertwining research topics:

1. Protein post-translational modifications, regulated proteolysis and ubiquitination

Proteins can undergo up to over 200 types of post-translational modifications (PTMs), which has tremendously expanded the chemical repertoire of 20 amino acids for proteins. Protein ubiquitination, the addition of one or multiple ubiquitin molecules to proteins, is one of the most “ubiquitous” PTMs that modulate the proteins’ activity, localization, stability or interaction with other proteins. A primary function of ubiquitination is to target the proteins for degradation through a protease complex, the proteasome. Functions of the ubiquitin–proteasome system (UPS) dictate almost every aspect of cellular activities in both health and disease conditions (Hershko, A., Ciechanover, A., Varshavsky, A. 2000, The ubiquitin system. Nature Medicine 6, 1073-1081). In vivo, protein ubiquitination and degradation is delicately regulated through mechanisms that heavily involve crosstalk with other PTMs, either on the protein substrates or key components of the UPS (Hunter, T. 2007, Mol. Cell 28:730-8).

Advances in analytical techniques have opened the door to unraveling the functional significances of crosstalk between major PTMs. After discovering that Nitric Oxide, as a signal molecule, can directly target protein to degradation(Hu et. al. 2005 Nature), our research in the years to come will first focus on the interplay between protein ubiquitination and other regulatory PTMs that include, but are not limited to, :1) phosphorylation; 2) Glycosylation; 3) protein arginylation, a fundamental but yet under-explored PTM; 4) nitric oxide (NO)-mediated protein modifications. (See reference Hu et. al. 2008 PNAS and Hu et. al. 2005 Nature for more details). We start with transgenic cell lines or animal models for cancer and metabolic diseases.

Currently, we are also developing tools that will allow us to investigate into the multiple correlation between E3 Ub ligases and their protein substrates. Our research is proceeding with an emphasis on E3s whose mutations are closely associated with devastating diseases. Ub ligases in query include BRCA1 in breast cancer, E6-AP/Ube3a in cervical cancer and Angelman Syndrome etc.

2. Protein-based molecular recognitions

There is one common feature that all living organisms always share: generating signal molecules while responding to environmental cues. This is all made possible through specific recognitions between, often time protein-based, molecules in close spatial proximity. We aim to decipher mechanisms underlying such molecular recognitions, develop tools to visualize them, and apply these tools into studies of fundamental biological problems and pathology of diseases. We hope to bring advents in the areas of disease diagnosis and therapeutic methodology, and new insights into fundamental biological problems as well.

Currently under development are a battery of biosensors: gas sensors that are engineered to visualize the gaseous molecules during cell signaling, and sensors that bear promises to illuminate genomic or transcriptomic events.

 

Biography
07/2009- present     Principal Investigator, Institute of Biochemistry and Cell Biology, SIBS, CAS
03/2006-07/2009      Senior Research Fellow, Division of Biology, California Institute of Technology, Pasadena, CA
03/2001-03/2006      Postdoctoral Scholar, Division of Biology, California Institute of Technology, Pasadena, CA
08/2000-03/2001      Assistant Investigator, Shanghai Institute of Biochemistry & Cell Biology, SIBC, CAS, China
08/2000              Ph.D. Biochemistry & Molecular Biology, Shanghai Institute of Biochemistry & Cell Biology, SIBC, CAS, China
07/1995              B.S Biology, Anhui Normal University, Anhui, China  

Selected Publications
1. Hu R.G., Wang H., Xia Z., Varshavsky, A. (2008) The N-end rule pathway is a sensor of heme. Proc. Natl. Acad. Sci. USA. 105(1):76-81.
2. Hu R.G粗体., Brower, C. S., Wang, H., Davydov, I. V., Zhou, J., Kwon, Y. T. and Varshavsky, A. (2006) Arginyl-transferase, its specificity, putative substrates, bidirectional promoter, and splicing-derived isoforms. J. Biol. Chem. 281(43): 32559-73.
3. Graciet, E. Hu R.G., Piatkov, K., Rhee, J. H., Schwarz, E. M. and Varshavsky, A. (2006) Aminoacyl-transferases and the N-end rule pathway of prokaryotic /eukaryotic specificity in a human pathogen. Proc. Natl. Acad. Sci. USA 103, 3078-3083.
4. Hu R.G., Sheng J., Qi X., Xu Z., Takahashi T.T. and Varshavsky A., (2005) The N-end rule as a nitric oxide (NO) sensor, controlling the levels of multiple regulators. Nature. 437(7061):981-6. (Article)
(Comments see "Yet another job for a gas". Nature Review Mol .Cell Biology, Lesley Cunliffe, Vol. 6, November 2005: 822-823; "No link to destruction". Journal of Cell Biology, Vol. 171, No. 3, 2005: 406-407; "Nitric Oxide Signaling: NO Spells End for RGS Proteins" Science STKE, Vol. 2005, Issue 306, October 18, 2005: tw362; "Protein Degradation and NO: The beginning of the N-End". feature article, Nature AFCS, Monica Hoyos- Flight, October 2005.)
5. Kwon YT, Kashina AS, Davydov IV, Hu R.G., An JY, Seo JW, Du F, Varshavsky A. (2002) An essential role of N-terminal arginylation in cardiovascular development. Science. 5;297(5578):96-9. 
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