- Understanding of how cellular stress may eventually result in the alteration or loss of cellular functions
My current research interest is in the understanding of how cellular stress may eventually result in the alteration or loss of cellular functions: an underlying causative factor in chronic diseases. Cellular stress can arise due to various reasons, such as the perturbation/loss of intra- or extracellular homeostasis, the production of toxic metabolites, damages of intracellular macromolecules, etc. Mechanisms exist in cells that are able to sense and to respond to the presence of cellular stress. Such mechanisms are crucial to the health and development of a multi-cellular organism.
Our group is particularly interested in oxidative stress response mechanisms in cells. Oxidative stress is due to the accumulation of reactive oxygen species (ROS). Firstly, we would like to understand how ROS might function as signaling molecules that regulate gene expression at the post-transcriptional level. We demonstrated previously that treatment of cells with a synthetic retinoid known as fenretinide resulted in the expression of the growth-arrest and DNA-damage inducible (Gadd153) gene. Further study of this effect of fenretinide revealed that this retinoid led to the stabilization of the Gadd153 mRNA, most probably through an ROS-dependent mechanism. We are currently investigating the molecular components that are involved in the ROS-mediated regulation of mRNA-stability.
Secondly, we are also interested in the metabolism of ROS with a view to understanding how cells might be protected from ROS-induced cellular stress and how ROS might function as an intracellular messenger. The thioredoxin reductase and its substrate thioredoxin are both involved in the redox metabolism of ROS, utilizing electrons donated by NADPH. Under normal circumstances, this system contributes to the overall capacity of a cell to scavenge ROS. Initially known for its role in ROS metabolism, increasing evidence suggests that thioredoxin reductase/thioredoxin system is involved in the growth and development of normal and abnormal cells. Our studies in the thioredoxin reductase/thioredoxin system include the investigation of the regulation of intracellular thioredoxin reductase activity at the transcription and post-translational level. Ongoing projects are aimed to elucidate the signaling pathways that regulate the transcription of the thioredoxin reductase gene and the stability of the enzyme protein.
Another topic that is of interest to us is apoptosis: a response option that may be selected by cells in the event of stress. Previously, we obtained evidence that the ?-opioid receptor agonist (U50488H) was a potentiating agent for apoptosis through a pathway that apparently involved the Inositol-1,4,5-trisphosphate/Ca 2+-signaling pathway. We are currently investigating how such a pathway may act as a signaling pathway for apoptotic cell death.
- The role of post-transcriptional regulation in cellular stress response
- Kappa-opioid receptor and the regulation of apoptosis
- Jing Qin, Mulin Jun Li, Panwen Wang, Nai-Sum Wong, Maria P. Wong, Zhengyuan Xia, George S. W. Tsao, Michael Q. Zhang and Junwen Wang, (2013) "ProteoMirExpress: inferring microRNA-centered regulatory networks from hgh throughput proteomic and mRNA expression data." Mol Cell Proteomics, 12(11):3379-87
- Jing Liu, Aimin Xu, Karen Siu-Ling Lam, Nai-Sum Wong, Jie Chen, Peter R Shepherd and Yu Wang, (2013) "Cholesterol-induced mammary tumorigenesis is enhanced by adiponectin deficiency: role of LDL receptor upregulation." Oncotarget, 4(10):1804-18
- Janice B. B. Lam, Kim H. M. Chow, Aimin Xu, Karen S. L. Lam, Jing Liu, Nai-Sum Wong, Randall T. Moon, Peter R. Shepherd, Garth J. S. Cooper and Yu Wang, (2009) "Adiponectin haploinsufficiency promotes mammary tumor development in MMTV-PyVT mice by modulation of phosphatase and tensin homolog activities." PLoS ONE 4(3): e4968. doi:10.1371/journal.pone.0004968
- Wai Lung Lai and Nai-Sum Wong, (2008) "The PERK/eIF2a signaling pathway of Unfolded Protein Response is essential for N-(4-hydroxyphenyl)retinamide (4HPR)-induced cytotoxicity in cancer cells." Exp Cell Res, 314(8): 1667-82
- Wai Lung Lai and Nai-Sum Wong, (2005) "ROS mediates 4HPR-induced post-transcriptional expression of Gadd 153 gene." Free Rad Biol Med, 38(12):1585-93
- Nai-Sum Wong , Catherine Tei-Mei Diao, Tak-Ming Wong (2003) “The Over-expression of Bcl-2 antagonizes the pro-apoptotic function of the Kappa-Opioid receptor.” Annals of the New York Academy of Sciences, 1010:358-60
- Yuhe Xia, Nai-Sum Wong, Wang-Fun Fong and Henk Tideman, (2002) “The Up-regulation of Gadd153 expression in the apoptotic signaling of N-(4-hydroxyphenyl)retinamide (4HPR).", Int J Cancer, 102(1):7-14
- Elyaman W, Terro F, Wong NS, Hugon J., (2002) “In vivo activation and nuclear translocation of phosphorylated glycogen synthase kinase-3beta in neuronal apoptosis: links to tau phosphorylation.” Eur J Neurosci, 15(4):651-60
- Xiao-Chun Yu, Tie-Mei Diao, Jian-Ming Pei, Wei-Min Zhang, Nai-Sum Wong, and Tak-Ming Wong, (2001) "kappa-opioid receptor agonist inhibits the cholera toxin-sensitive G-protein in the heart." J Cardiovasc Pharmacol, 38:232-239
- Catherine Tei-Mei Diao, Lan Li, See-Yan Lau, Tak-Ming Wong and Nai-Sum Wong (2000) "kappa-opioid receptor potentiates apoptosis via a phospholipase-C pathway in the CNE2 Human Epithelial Tumor Cell Line." Biochim Biophys Acta, 1499(1-2):49-62
- Kappa-opioid receptor mediated cellular stress response: the role of inositol 1, 4,5-trisphosphate and diacylglycerol