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Gender-specific differences and estrogen’s role in inflammatory diseases is not well understood. Although women in their fertile age are more prone to autoimmunity, they experience lower rates of infections and inflammatory disease (e.g atherosclerosis, type 2 diabetes). Our lab has a longstanding experience in in vivo (ovariectomy and estrogen replacement), ex vivo (isolated organs) and in vitro studies of estrogen receptors (ER) as targets of novel therapeutics. Current research focuses on the effects of endogenous estrogens (menstrual cycle, menopause, endocrine disease associated with atherosclerosis such as PCOS, obesity) as well as of exogenous ER modulators on 1) human monocyte-derived macrophage activation phenotypes and functions, 2) cell-cell interaction (macrophage-endothelial cell/fibroblast) in relation to angiogenesis (in collaboration with Dr. Trevisi) and fibrosis and 3) metabolic/signaling pathways. We are investigating signaling proteins downstream of ER activation, with particular emphasis on estrogen-mediated regulation of cell metabolism. The long-term goal is to identify selective estrogen-receptor modulators, which trigger beneficial responses in chronic inflammatory diseases without major side effects. 
Bolego, Ferri

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Endothelial cells as well as cells of the innate immune system (macrophages) play a pivotal role in the regulation of different phases of the inflammatory process (i.e. early inflammatory response as well as resolution phase) also through the release of lipid mediators derived from the metabolism of omega-3 (alpha linolenic acid/DHA) and omega-6 (arachidonic acid) polyunsaturated fatty acids (PUFAs). Recent in vitro and in vivo studies demonstrated an anti-inflammatory, pro-resolutive role of COX-derived lipid mediators in the presence of aspirin and DHA. Our research is aimed at assessing how the lipid signatures of human endothelial cells and monocyte-derived macrophages exposed in vitro or in vivo to omega-3 PUFAs and metabolites thereof affect functional responses (e.g. angiogenesis/fibrosis) also in the setting of chronic diseases such as type 2 diabetes/obesity and COPD. Angiogenesis experiments are performed in collaboration with Dr. Trevisi.
Bolego, Ferri

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Since the discovery of the pleiotropic effect of the HMG-CoA reductase inhibitors (statins) there has been great interest in understanding the basic molecular mechanism regulating the cholesterol homeostasis and the atherosclerotic plaque development. More recently, the discovery of the pivotal role of PCSK9 on the regulation of the LDL-cholesterol level has opened a new era of pharmacological treatment of hypercholesterolemia and associated cardiovascular diseases. The main research interest of our laboratory is the discovery of the biological function of PCSK9 on lipid, glucose and cholesterol metabolism as related to atherosclerosis, diabetes and metabolic syndrome diseases. We utilize in vitro pharmacological and biological tools for dissecting the metabolic pathways linking PCSK9 and cholesterol or glucose metabolism. In addition, we corroborate our findings by analyzing biopsies and plasma samples received from the clinics of healthy subjected and patients affect by coronary heart disease, metabolic syndrome and type 2 diabetes.

Ferri, Bolego