Faculty & Staff Directory
Department of Biology
University of South Carolina
|Office:||PSC 623||Phone Number:||803-777-1551||Email:||firstname.lastname@example.org|
Cyclooxygenase (COX) is a key enzyme in the prostanoid biosynthesis. Prostanoids are lipid signaling molecules that regulate various physiological processes such as inflammation, pain mediation, renal function, reproduction, and gastrointestinal integrity. Once synthesized, prostanoids are released outside the cells and bind to their specific receptors, stimulating various downstream signaling molecules.
There are two isoforms of cyclooxygenase: COX-1 and COX-2. Although these enzymes catalyze a nearly identical reaction, their expression pattern is distinctly different. COX-1 is constitutively expressed in many tissues and is thought to play roles in tissue homeostasis. In contrast, COX-2 has a low or undetectable level of basal expression in most normal tissues and cell types. However, its expression is highly induced during infection or inflammation, suggesting that COX-2 plays a role in inflammatory responses. In addition, COX-2 expression is highly induced by various environmental insults such as UV, hypoxia, heat shock, and xenobiotics. Therefore, increased expression of COX-2 may be an indicator of cellular and environmental stresses. Consistent with this notion, aberrant COX-2 expression is frequently observed in many types of human diseases such as inflammation, cancer, cardiovascular diseases, and neurodegenerative diseases.
Our laboratory is interested in understanding the pathophysiological roles of COX-2 in human diseases such as cancer and arthritis. We have developed a COX-2 transgenic mouse model in which COX-2 expression can be achieved in any cell types by a targeted Cre recombinase activity. Using this model, we have shown that aberrant expression of COX-2 induces cell death and p53 expression, resulting in skeletal malformation. We are now in the process of developing chondrocyte-specific, inducible COX-2 transgenic mouse model to study the role of increased COX-2 expression in osteoarthritis. Additionally, we study the association of COX-2 signaling with p53 pathway using cellular and molecular tools, and knockout mouse models
Vaish V., Kim J., and Shim M. “Lentivirus-mediated Somatic Recombination and Development of a Novel Mouse Model for Sporadic Colorectal Cancer” Genes, Chromosomes and Cancer (In press) 2016
Kim J. and Shim M. “COX-2 inhibitor NS-398 suppresses doxorubicin-induced p53 accumulation through inhibition of ROS-mediated Jnk activation” Molecular Carcinogenesis (In press) 2016
Chun K. and Shim M. “EP2 Induces p38 Phosphorylation via the Activation of Src in HEK 293 Cells.” Biomol Ther. 23:539-48, 2015
Kim J. and Shim M. “Prostaglandin F2α receptor (FP) signaling regulates Bmp signaling and promotes chondrocyte differentiation.” Biochim Biophys Acta. 1853:500-12, 2015
Wang X, Chrysovergis K, Bienstock RJ, Shim M, Eling TE. 2012. The H6D variant of NAG-1/GDF15 inhibits prostate xenograft growth in vivo. Prostate.
Shim M, Foley J, Anna C, Mishina Y, Eling T. 2010. Embryonic expression of cyclooxygenase-2 causes malformations in axial skeleton. J Biol Chem. 16206-17.
Shim M., Eling T.E. 2008. Vitamin E Succinate (VES) induces NAG-1 expression in a p38 kinase dependent mechanism. Mol Cancer Ther. 961-71.
Shim M., Eling T.E. 2005. PKC-dependent regulation of NAG-1/PLAB/MIC-1 expression in LNCaP prostate carcinoma cells. J Biol Chem. 18636-18642.