The Wagner lab studies how blood cells respond to injury or stressful situations and initiate defensive or reparatory processes. Specifically, they investigate the crucial role of cellular adhesion interactions in the response process, as well as the regulation of the adhesion molecules involved in normal physiology and in pathological situations.
Blood cells called platelets form a platelet plug to stop bleeding. Leukocytes (white blood cells) emigrate from the blood vessels to fight invading infectious agents and/or release biological mediators that stimulate the function of the surrounding organ to better respond to the demands of stress. All this requires activation of adhesive processes that allow vascular cells to bind to each other and to cells in the organs where the leukocytes emigrate.
To advance their work, Wagner and colleagues have engineered mice lacking platelet, endothelial, or leukocyte adhesion receptors. These animals permit modeling of human diseases with similar genetic defects and evaluation of the performance of mutant blood cells in live vessels through intravital microscopy. The Wagner lab studies platelet adhesion to the vessel wall, which can lead to thrombus formation and sometimes embolization. Recently, they observed that nuclear DNA ejected by stimulated leukocytes (NETs) greatly enhanced pathological thrombosis and organ injury during inflammation.
Wagner and colleagues also are researching the importance of adhesion molecules in inflammatory processes such as atherosclerosis, the narrowing of arteries. They have observed that leukocytes recruited to the liver help to regulate fat metabolism and help to prevent obesity. The lab began to visualize blood vessels in the brain and study mechanisms involved in the formation of the blood brain barrier, which prevents uncontrolled leakage of molecules from the blood into the central nervous system. They ask, do malfunctions of brain microcirculation contribute to the etiology of neurodegenerative diseases such as Alzheimer's? Using animal models, they are testing new ways to modulate blood brain barrier permeability and to evaluate inhibitors of adhesion molecules as possible agents to prevent heart disease and/or thrombosis.
About Denisa Wagner
Dr. Wagner received her Diploma of Biochemistry from the Université de Geneve, Switzerland and Ph.D. in Biology from the Massachusetts Institute of Technology. She served on the faculty at the University of Rochester, NY and Tufts University School of Medicine before coming to Harvard Medical School in 1994. She is an Edwin Cohn Professor of Pediatrics with the Center for Blood Research, a senior investigator in the Program in Cellular and Molecular Medicine, and a member of the Division of Hematology/ Oncology at Boston Children's Hospital.
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