daniel a. lawrence, phd
Frederick G L Huetwell Professor of Basic Research in Cardiovascular Medicine
Professor, Cardiovascular Medicine
Professor, Molecular and Integrative Physiology
Dr. Lawrence received his Ph.D. in Molecular Biology from Umeå University, Umeå Sweden in 1989 and completed his postdoctoral training at the University of Michigan from 1989 until 1992. He was then appointed Research Investigator in the Department of Internal Medicine at the University of Michigan in 1992. In 1995, Dr. Lawrence moved to the American Red Cross Holland Laboratory for Biomedical Sciences where he was appointed Scientist I (Assistant Professor) in the Department of Biochemistry, and served a concurrent appointment as Adjunct Assistant Professor in the Department of Biochemistry and Molecular Biology at George Washington University in Washington DC. He joined the University of Maryland School of Medicine in 2004 as Professor in the Department of Surgery and in 2005 returned to the University of Michigan as Professor of Cardiovascular Medicine.
Dr. Lawrence’s laboratory studies the role of proteases and their inhibitors in health and disease. Primary areas of interest focus on the vascular biology of the central nervous system (CNS) and disorders such as stroke, as well as the development of peripheral vascular disease.
He has over 25 years of experience in vascular biology and over 15 years of experience with animal models of stroke, and other CNS disorders. Studies range from very basic questions such as how binary 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. He uses combinations of biochemical, molecular, and genetic approaches to study how specific molecular interactions regulate function, and then applies 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 CNS. These studies involve animal models of stroke and seizures and study 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.