Pathology and Molecular Diagnosis

Biography

Biography: Dipak P Ramji

Abstract

Atherosclerosis, the underlying cause of heart attack and stroke, is an inflammatory disorder of the vasculature regulated by both the innate and adaptive immune systems. Cytokines play a pivotal role in controlling the inflammatory response in atherosclerosis and regulate all the different stages in disease progression.Current approaches to target pro-inflammatory cytokines include neutralization using blocking antibodies or soluble decoy receptors and the use of specific inhibitors against key components of intracellular signaling pathways. In contrast, approaches for anti-atherogenic cytokines include their local delivery and the use of agents that augment their expression/actions. Numerous cytokines are expressed in atherosclerotic lesions and it is therefore essential that their actions in disease progression are fully understood to validate their therapeutic potential and to identify potentially new targets or approaches for therapeutic intervention.

My laboratory has recently been investigating cytokine signaling in atherosclerosis, particularly in macrophagesthat play key roles in all stages of disease progression, using a combination of in vitro and in vivo approaches. Novel insights have been obtained on the actions ofthe cytokines interferon-gamma, transforming growth factor-beta, interleukin-33 and tumour necrosis factor-like protein 1A on key macrophage processes in atherosclerosis (e.g. foam cell formation, regulation of inflammation). For example, we have identified a key role for extracellular signal-regulated kinase: signal transducer and activator of transcription-1 serine 727 phosphorylation axis in the control of macrophage foam cell formation and the regulation of pro-inflammatory gene expression by interferon-gamma. The outcome of our studies on different cytokines will be presented in the context of current therapies and future developments in this field.