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The Lawrence laboratory studies the role of proteases and their inhibitors in health and disease. Primary areas of interest focus on the vascular biology of the CNS and disorders such as stroke; and on the development of peripheral vascular disease. Studies range from very basic questions such as how binary protein:protein interactions regulate physiologic processes to complex animal models of disease. The principal targets of this work are members of the serine protease inhibitor (serpin) family of proteins, their target proteases, including tissue plasminogen activator (tPA), and the downstream protease substrates. We use combinations of biochemical, molecular, and genetic approaches to study how specific molecular interactions regulate function, and then apply this information to in vivo models of disease to test the importance of these interactions in complex physiologic processes. One area of interest examines the basic structure function relationships of the serpin mechanism using PAI-1 and neuroserpin as model serpins. Another analyzes PAI-1's role in the development of vascular disease in both in vitro cell culture systems and in vivo. A third and major area of study examines the functions of neuroserpin and its target protease tPA, and the tPA substrate platelet derived growth factor C (PDGFc) in the central nervous system (CNS). These studies involve animal models of stroke, seizures or traumatic brain injury, and investigates the roles of these proteins in the regulation of the blood brain barrier. The regulation of neuronal communication processes by neuroserpin and tPA are also studied using in vitro cell cultures of primary neurons, ex vivo electrophysiological studies, and in vivo in mice.