Systems approach to target discovery for inflammatory vascular disease

Systems approach to target discovery for inflammatory vascular disease: A focus on macrophage activation and heterogeneity

Abstract

Pro-inflammatory activation of macrophages contributes to the pathogenesis of atherosclerosis; however, its underlying mechanisms remain incompletely understood. Despite the availability of potent drugs for modifiable risks, complications of atherosclerosis remain global health threats. To challenge residual risk, my group explores novel mechanisms for macrophage activation as an important first stride towards the development of new therapies. While many potential targets have been proposed by others and us, the science community recognizes that, because complex mechanisms of human diseases involve intertwined crosstalk among many molecules and pathways, understanding individual and collective contributions of components to macrophage activation is critical. Seemingly promising candidates that are established by a conventional reductionist approach may thus ultimately fail. We indeed face low success rates of the clinical development of new drugs after lengthy preclinical efforts for identifying and validating new targets. To facilitate the discovery process and improve success rates, we use a systems approach, involving multi-omics, computational prediction via network analysis, and artificial intelligence. We also focus on the biology of macrophage heterogeneity as examined by single cell analysis, as a path to precision medicine for cardiovascular diseases. My lecture will showcase novel targets for macrophage activation we have identified through such a strategy.

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