Nur77 and FHL2: Novel players in vascular and immune disease

The nuclear receptor Nur77 is an early response gene that is induced by diverse extracellular signals in a wide range of tissues and cultured cells. It has been implicated in the regulation of genes involved in metabolic disease, adipogenesis, inflammation, and vascular disease. FHL2/DRAL/SLIM3 is a LIM-only protein that has been shown to interact with many proteins and acts as a co-activator or co- repressor depending on the cell-type and cellular context. It is a crucial adaptor protein and plays a pivotal role in a range of physiological and pathological processes, including proliferation, migration, differentiation and apoptosis. The aim of this thesis is to increase our understanding of fundamental pathways critical in vascular diseases including atherosclerosis, restenosis, coagulation, and immune diseases including asthma, airway inflammation and schistosomiasis. To achieve this goal, we performed numerous distinct studies on the role of nuclear receptor Nur77 and LIM-only protein FHL2 using mouse models and several cell types. In this thesis, functional properties of Nur77 and FHL2, as well as their impact on multiple signaling pathways in vascular and immune disease were studied. These research efforts are ultimately directed at designing novel therapeutic strategies that may aid in mitigating the development of vascular and immune disease.