Macrophages have a remarkable ability to adapt their intracellular metabolism in response to a diverse array of extracellular signals, and these metabolic changes are critical for the phenotypic polarization required for their multiple functions. These projects aim to understand the interplay between intracellular lipid metabolism and activation of the inflammatory response. This project is currently funded by R01AI168194.
Macrophage acetyl-CoA carboxylase (ACC) in the regulation of the acute inflammatory response
Acetyl-CoA carboxylase (ACC) enzymes are key regulators of de novo fatty acid synthesis through the conversion of acetyl-CoA to malonyl-CoA. Using a myeloid-specific ACC1/ACC2 knockout mouse, we identified a role for ACC in metabolic and transcriptional activation of macrophages in response to proinflammatory stimuli such as bacterial lipopolysaccharide (LPS).
Myeloid ACC in cardiometabolic diseases
Given the translational relevance of pharmacologic ACC inhibition in cardiometabolic disease, we are also keen to explor a potential role for myeloid ACC in models of diet-induced obesity, NASH, and heart failure.
ACC1 and ACC2 roles in macrophage function
Using genetic and pharmacologic approaches we are interested exploring potential individual roles for ACC1 and ACC2 in metabolic and transcriptional control of induction and resolution of the acute inflammatory response.