Personal HistoryI completed my doctorate in Biochemistry at Rice University and postdoctoral training in cell biology at Baylor College of Medicine, Houston Texas. I began my research into serine protease inhibitors and the plasminogen activation system when I took a position at a biotechnology company in Sydney Australia. In 1988, I joined the Oncology Program at the Queensland Institute of Medical Research, in Brisbane Australia where my interest in membrane anchored serine proteases evolved. I returned to the United States in 2001 to join the Vascular Biology research program at the Holland Laboratory of the American Red Cross in Rockville Maryland. In 2004, I joined the faculty of the University of Maryland, School of Medicine as Professor of Physiology and Associate Director of the Center for Vascular and Inflammatory Diseases. My research programs have been continuously funded and I have been supported by the Lance Armstrong Foundation and the National Institutes of Health. I am active in post-graduate training and am director of the Molecular and Cellular Cancer Biology track in the Molecular Medicine Graduate Program. I am currently associated with training grants in Transfusion Medicine and Membrane Biology from the National Institutes of Health. I am a member of the Publications Committee of the American Society for Biochemistry and Molecular Biology, and a member of the Editorial Board of the Journal of Biological Chemistry. Research InterestsOur research is focused on signaling mechanisms involved in vascular disease and cancer. The long term goal of our research is to better understand the biology of serine proteases and their inhibitors (serpins) and to investigate their potential as targets for diagnostic applications or rational drug-based therapies for cancer and vascular diseases. Proteases are powerful hydrolytic enzymes that mediate cleavage, activation and degradation of many cellular proteins, and therefore play fundamental roles in virtually every aspect of cell behavior, including survival, growth, differentiation, and malignant transformation. Inappropriate proteolysis can significantly impact disease progression, thus proteases represent attractive targets for intervention in a number of disorders and diseases. The serine proteases are one of the largest and most highly conserved multigene families. These proteases are distinguished by the fact that a serine residue plays a critical role in the catalytic process. Members of the serine protease family are well recognized to initiate and control complex biological systems, such as blood coagulation, wound healing, digestion, immune responses, reproduction and development. Recently, through genomics and database mining approaches, the existence of membrane anchored serine proteases, a unique group of molecules that contain serine protease domains in addition to multiple other structural domains, and which include hydrophobic membrane-anchoring sequences has been recognized. We currently know very little about these enzymes and their activities. Disruption or mutation of several of the genes encoding these proteases are directly associated with inherited genetic diseases, and while many of the membrane anchored serine proteases show restricted tissue distribution in normal cells, their expression is widely dysregulated during tumor growth and progression. A detailed understanding of these proteases and how they interact with other proteases and cell associated signaling molecules is necessary for our understanding of cell growth and regulation as it relates to cancer, angiogenesis and other diseases. Our current research interests include:
Lab Techniques and EquipmentWe generate and make extensive use of knockout and transgenic mouse models for determining essential gene functions, as well as incorporate both microarray and proteomics approaches for differential molecular analyses. We also employ a range of mouse models for the study of tumor growth and metastasis, analysis of new blood vessel formation (angiogenesis) and sperm function. Recombinant DNA techniques, including cloning, mutagenesis and heterologous expression are used routinely and are coupled with state-of-the-art cell biological analyses such as confocal fluorescence microscopy. We produce recombinant proteases using insect cells for analyses of their biochemical and enzymatic properties. We also utilize molecular approaches such as immunoblotting, immunoprecipitation and reporter gene assays to study cellular signaling pathways involved in cell growth regulation and differentiation.
Laboratory Personnel :
Sarah Netzel-Arnett (Research Associate) · Marguerite Buzza (C. J. Martin Fellow, Publications
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