Christopher K. Glass

Discovered that the PPARy negative regulates macrophage activation and demonstrated anti-inflammatory, anti-atherogenic, and anti-diabetic functions of macrophage PPARy in vivo. Molecular analysis of the interaction of PPARy with coactivators provided the structural basis of the 'charge-clamp' model for ligand-dependent nuclear receptor/coactivator assembly. Analysis of genome-wide transcriptional responses to inflammatory stimuli revealed that the distinct molecular mechanisms are used by nuclear receptors to negatively regulate the expression of cohorts of genes differentially integrating response at the level of individual promoters. His discovery that PPARy and liver X receptors (LXRs) exert anti-inflammatory effects by preventing the signal- and actin-dependent removal of NCoR and SMRT corepressor complexes from inflammatory response genes established the concept that NCoR/SMRT complexes impose a transcription checkpoint that functions to integrate pro/anti-inflammatory signals. Most recently, identified Nurr1/CoREST and estrogen receptor beta/CtBP-dependent repression pathway in microglia and astrocytes that function as negative feedback loops to attenuate responses to inflammatory signals that would otherwise result in neurotoxicity.