{"id":8894,"date":"2013-09-17T16:13:04","date_gmt":"2013-09-17T20:13:04","guid":{"rendered":"https:\/\/www.bumc.bu.edu\/ppb\/?page_id=8894"},"modified":"2022-10-18T12:15:02","modified_gmt":"2022-10-18T16:15:02","slug":"ldor","status":"publish","type":"page","link":"https:\/\/www.bumc.bu.edu\/ppb\/education\/pharmacology\/training-program\/laboratories\/ldor\/","title":{"rendered":"Laboratory of Diabetes and Obesity Research"},"content":{"rendered":"

Metabolic Syndrome, Obesity, Diabetes and Innate Immunity<\/em><\/strong><\/p>\n

Research focus:<\/strong><\/p>\n

1. Understanding the role of neutrophils in the development of obesity-related systemic inflammation, tissue damage and remodeling. <\/em><\/strong>Using a quantitative serum proteomic approach, we discovered that obesity leads to the imbalance between serine protease neutrophil elastase and serine protease inhibitor alpha-1-antitrypsin both in mouse models and human subjects. Our studies also revealed that obesogenic diet feeding induces alternation of hematopoiesis with dramatic increase of pro-inflammatory neutrophil production and pro-inflammatory phenotype in mice. Interestingly, mice lacking of neutrophil-specific protease neutrophil elastase are resistant not only to diet-induced neutrophil production but also obesogenic diet-induced vascular damage, adipose inflammation and fibrosis, nonalcoholic steatohepatitis (NASH), and insulin resistance. We are in the process to study how nutritional factors are involved in the regulation of neutrophil differentiation and how this process is related to the development of systemic inflammation, NASH, adipose tissue fibrotic remodeling, and metabolic disorders.<\/p>\n

2. Neutrophils play pivotal role in obesity-related vascular injury and vascular aging.<\/em><\/strong> Our study revealed that neutrophils contribute to obesity-related vascular leakage and immune cell infiltration in adipose tissue by releasing neutrophil elastase. The latter increases vascular permeability and leukocyte extravasation through activating protease activated receptor 2 (PAR2) and Rho kinase signaling in vascular endothelial cells. Our recent studies also revealed that neutrophils are involved in vascular aging and related arterial stiffness. We are currently investigating molecular and cellular mechanisms by which obesity and aging regulate the interactions between neutrophils and vascular cells.<\/p>\n

3. CDP138 and its signal networks related to glucose and lipid metabolisms in adipose tissues.<\/em><\/strong> Using a SILAC-based phosphoproteomic analysis, we identified a new phosphoprotein CDP138 that is involved in the regulation of vesicle trafficking. We are using the knockout mouse models to study the signal network of CDP138 and its role in the regulation of catecholamine release, fat browning, thermogenesis, and lipid metabolisms.<\/p>\n

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