Lan Huang
Developmental & Cell Biology, School of Biological Sciences
Physiology & Biophysics, School of Medicine
Phone: (949) 824-8548
Email: lanhuang@uci.edu
Huang lab web page
http://www.faculty.uci.edu/profile.cfm?faculty_id=5268
Lan Huang
Dr. Huang’slab is interested in developing and employing mass spectrometry-based proteomics approaches to identify and characterize components of macromolecular machines and their posttranslational modifications, and map their interacting networks and structural topology in order to provide comprehensive information to elucidate the functions of these macromolecular machines. To this end, they have utilized the proteasome complex as their model system due to its enormous importance in health and medicine.
The 26S proteasome is a macromolecular machine responsible for ubiquitin/ATP dependent protein degradation in both cytosol and nucleus. It consists of two distinct sub-complexes, the 20S proteasome complex responsible for various proteolytic activities; and the 19S regulatory complex believed to render ATP-dependent proteolysis of ubiquitinated substrates. Recognition and degradation of ubiquitinated substrates including cell cycle regulators, tumor suppressors and transcription factors by the 26S proteasome are tightly regulated to maintain normal cell growth. Therefore, aberration of this pathway can lead to tumorigenesis. Previous studies have shown that the proteasome components change in various cancer cells and most of them are overexpressed in blood from cancer patients compared to normal patients. Therefore, the detailed proteasomal profiling may represent a group of putative protein biomarkers of cancer. In addition to its potential role as biomarkers for diagnostics, the proteasome has recently become an attractive therapeutic target. Velcade (bortezomib, PS-341), a potent and selective proteasome inhibitor, has been evaluated for the treatment of various cancers, and has been approved by the FDA for the treatment of relapsed and refractory multiple myeloma. Recently, it was reported that Velcade can sensitize pancreatic cancer cells to ER stress-induced apoptosis and strongly enhance the anticancer activity of cisplatin, suggesting that Velcade may be used for the treatment of the pancreatic cancer in combination with chemotherapy to increase the survival rate of the patients. However, the mechanism of a general proteasome inhibitor for cancer treatment remains elusive and complex since blockage of the proteasome-dependent degradation affects many regulatory pathways in the cellular processes. Thus, further understanding of the proteasomal profile and proteasome interacting network in cancer cells may offer new molecular targets for specific inhibition of the proteasome degradation pathways to achieve more effective treatment of cancers. Towards this goal, here are several related projects:
1) Developing and employing integrated proteomic approaches for efficient isolation of the proteasome complexes, comprehensive profiling of the complex composition, and modification and interaction network at different cell cycle phases to understand how the proteasome is regulated during cell cycle progression.
2) Investigating the sensitivity and regulation of the proteasome upon oxidative stress in prostate cancer cells.
3) Global profiling of Nedd8 conjugated and associated protein in prostate cancer cell.
Selected Publications:
Wang, X., Chen, C. F., Baker, P. R., Chen, P. L., Kaiser, P., and Huang, L. (2007). Mass spectrometric characterization of the affinity-purified human 26S proteasome complex. Biochemistry 46(11), 3553-65.
Wang, X., Guerrero, C., Kaiser, P., and Huang, L. (2007). Proteomics of proteasome complexes and ubiquitinated proteins. Expert Rev Proteomics 4(5), 649-65.
Wang, X., and Huang, L. (2008). Identifying dynamic interactors of protein complexes by quantitative mass spectrometry. Mol Cell Proteomics 7(1), 46-57.
Jones, J., Wu, K., Yang, Y., Guerrero, C., Nillegoda, N., Pan, Z. Q., and Huang, L. (2008). A targeted proteomic analysis of the ubiquitin-like modifier nedd8 and associated proteins. J Proteome Res 7(3), 1274-87. |
