Regulation of the group VI Ca2+ -independent PLA2

Tim Smith

Appointment Period: 2001-2002 / Grant Year: [17]

Both the Fas/FasL and TNFa/TNF receptor (TNFR) have been demonstrated to be essential in the regulation of the immune system by eliminating mature T cells and maintaining peripheral tolerance. Failure of either of these systems can cause auto-immune disorders leading to the development of leukemia. In addition, the loss of the Fas-induced apoptotic mechanism facilitates the emergence of highly proliferative tumor phenotypes, primarily leukemia, which are difficult to eliminate by cytotoxic and chemotaxic mechanisms. The changes to cytosolic and nuclear proteins and chromosomal DNA which occur during apoptosis have been well studied, but the role of phospholipid metabolism in the process is poorly understood.

PUBLICATIONS (resulting from this training)

Kokotos G, Six DA, Loukas V, Smith T, Constantinou-Kokotou V, Hadjipavlou-Litina D, Kotsovolou S, Chiou A, Beltzner CC, Dennis EA. (2004) Inhibition of group IVA cytosolic phospholipase A2 by novel 2-oxoamides in vitro, in cells, and in vivo. J Med Chem 47:3615-28.