2008 Faculty Researchers

Zezong Gu, MD, PhD

Subproteome of S-Nitrosylated Proteins: Putative Biomarkers and Therapeutic Targets for Parkinson’s Disease

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Department

Pathology and Anatomical Sciences

Office Location

M771-B, Medical Sciences Building

Phone #:

Office: (573) 884-3880
Fax: (573) 882-4612

E-Mail:

guze@health.missouri.edu

Summary

Nitric oxide (NO) is a signaling molecule that plays diverse roles in the regulation of biological processes ranging from development to disease. A major NO-mediated protein posttranslational modification is termed S-nitrosylation (coupling of an NO group to a reactive cysteine thiol to form an S-nitrosothiol or SNO), with great importance to biological regulation of proteins, akin to phosphorylation. Research in Gu Laboratory focuses on understanding the molecular mechanism of this redox modulation, particularly the roles of nitrosative and/or oxidative stress in cell signaling of protein folding and degradation, and their impact to neurological diseases like Parkinson’s disease (PD). The summer research fellow will participate in: (1) developing a proteomic strategy to identify novel S-nitrosylated proteins; and (2) seeking chemical evidence for their basis as biomarkers in PD models. Ultimately, this research may lead to develop a novel strategy for clinical applications of diagnosis and therapy.

Gu Laboratory has established and/or adopted various model systems, such as primary cell cultures, and in vivo PD animal models. Multi-disciplinary approaches used in the laboratory include microsurgery, animals with genetic deficits, protein biochemistry, molecular and cell biology, pharmacology, immunocytochemistry, confocal/deconvolution microscopy, and comprehensive proteomic strategies. These experimental approaches allow us to conduct translational research and investigate the mechanisms underlying aberrant proteolysis and neuronal cell death by environmental risk factors like oxidative/nitrosative stress. Such experience will help the trainee to build future careers in medicine and biomedical development. Suggested Readings:

Gu Z.Z., et al. Science 2002, 297:1186-90.

Gu Z.Z., et al. J. Neurosci. 2005, 25:6401-8.

Gu Z.Z., et al. Matrix Metalloproteinas in the Central Nervous System. pp. 67-83, Imperial College Press, July 2005, San Diego.

Yao D., et al. Proc. Natl. Acad. Sci. USA 2004, 101:10810-4.

Gu Z.Z., et al. Cell Death Diff. 2005, 12:1202-4. [A special issue for the 2004 Nobel Prize]

Uehara T., et al. Nature 2006, 441:315-7.

Lipton S.A., et al. Int’l Review Neurobiol. 2007, 82:1-27.