|Department Affiliations||Pediatrics, Biochemistry National University of Singapore|
|SOM Address||Room 312 550 N. Broadway|
In this laboratory we study the relationship between the cardiovascular gene family and the various phenotypic changes (cell proliferation,adhesion and apoptosis) that lead to the inititation and progression of atherogenesis. We are also interested in alternative medicine drug discovery to prevent atherosclerosis.Our model systems are cultured human cells of the vascualr wall and animal models of athersclerosis.We also employ transeosophageal MRI technology to image atherosclerotic plaques and their rupture and regression in collaboration with the JHU-SOM faculty. Our laboratory has discovered that multiple risk factors in atherosclerosis such as oxidized LDL, shear stress,nicotine,all converge upon a lactosylceramide synthase gene to produce lactosylceramide. In turn, lactosylceramide serves as a lipid second messenger that activates an “oxygen sensitive signal transduction pathway” leading to cell proliferation and cell adhesion. We are also focusing on the neutral sphingomyelinase gene that is upregulated by inflammatory molecules such as Fas Apo1(CD95) , tumor necrosis factor and stress that leads to apoptosis. Since apoptosis of the aortic smooth muscle cells is a hallmark in the pathophysiology of plaque rupture we want to understand its biochemical/molecular basis involving this gene/function. Our herbal drug discovery strategy involve purification and characterization of small molecules employing high-performance liquid chromatography,GC-MS technology. Such well characterized molecules are then employed to determine their efficacy in abrogating atherogenesis and plaque rupture employing animal models.
- Kolmakova.A and Chatterjee,S (2004) Apolipoprotien C-1 activates the neutral sphigomyelinase ceramide pathway to induce apoptosis in human aortic smooth muscle cells Art.Thr.Vasc.Biol 24:264-269
- Bhunia,AK.,Schwarzmann,G and Chatterjee,S(2002) GD3 recruits reactive oxygen species to induce cell proliferation and apoptosis in human aortic smooth muscle cells. J.Biol.Chem. 277-16,396-16,402.
- Gong,Nan Ling and Chatterjee,S.(2004) Lactosylceramide recruits Phospholipase A2 to induce platelet endothelial cell adhesion molecule(PECAM-1)expression and adhesion of endothelial cells to monocytes. Proc Natl Acad Sci.USA 101: 6490-6495
- Jan,J,T,Chatterjee,S and Griffin,D(2000) Sindbis virus entry into cells tirggers apoptosis by activating sphingomyeliase leading to the release of ceramide. J.Virology 74:6425-6432.