- Leadership Fellow (Institute of Cardiovascular and Medical Sciences)
The focus of my research is to investigate the role of inflammation in cardiovascular disease, particularly in atherosclerosis and obesity. The concept that atherosclerosis is a chronic inflammatory disease of the arterial wall is well established and I am interested in the growing number of novel IL-1 family cytokines that have been identified as critical regulators of inflammatory responses and CD4+ T cell differentiation. I have shown that the IL-1 family cytokine, IL-33, and its receptor ST2 can play a key protective role in systemic and vascular inflammation by polarizing CD4+ immune responses towards a Th2 profile (Miller et al, J Exp Med 2008). More recently, I demonstrated that IL-33 exerts protective metabolic effects during obesity in mice (Miller et al, Circ Res 2010) by inducing accumulation of Th2 cells in adipose tissue and polarization of adipose tissue macrophages towards an M2 alternatively activated phenotype (CD206+), a lineage associated with protection against obesity-related metabolic events.
A second focus is study of the role of microRNA regulation of inflammatory cells in obesity. Chronic low-grade inflammation involving adipose tissue and liver likely contributes to metabolic consequences of obesity such as type 2 diabetes (T2D). It is becoming increasingly apparent that in order to improve clinical intervention, a better understanding of regulatory mechanisms controlling inflammatory cells in metabolic tissues is required. MicroRNAs are emerging as key regulators of macrophage lipid metabolism within adipose tissue and liver and I am currently studying the role of several miRNA during obesity.