Core A: Animal Model Core The purpose of the Animal Model Core A is to provide each investigator of the PPG a wide array of animal models to assess lipid metabolism, thrombosis, and related vascular disorders. Project 1) Daniel A. Lawrence, Ph.D., Professor of Cardiovascular Medicine, Department of Internal Medicine: Characterization of a Novel Role for PAI-1 in Lipid Metabolism. Core A will provide surgical support of Dr. Lawrence's in vivo experiments as outlined in this grant application. Core A will also be responsible for the cellular isolation of murine macrophages and adipocytes for in vitro experiments outlined in Project 1 for experiments evaluating the role of PAI-1 in lipid metabolism for Dr. Lawrence. Project 2) Thomas W. Wakefield, M.D., Head, Vascular Surgery Section, Department of Surgery: Role of PAI-1 in Venous Thrombogenesis. Core A will provide three animal models of venous thrombosis for in vitro testing for Project 2. These animal models include the following: 1) Inferior Vena Cava (IVC) Stenosis Model of Venous Thrombosis and 2) IVC ligation Model of Venous Thrombosis. Core A will perform all surgical procedures for experiments outlined by Dr. Wakefield and Dr. Peter K. Henke in Project 2. Project 3) David J. Pinsky, M.D., Chief, Cardiovascular Medicine, Department of Internal Medicine: Thrombotic/fibrinolytic Balance in Coronary Transplant Vasculopathy. Animal Model Core A will provide surgical support of Dr. Pinsky's murine in vivo experiments as outlined in this grant application. Core A will facilitate the acquisition of mouse echocardiograph images in the proposed transplant associated coronary artery disease (TCAD) experiments. Animal Model Core A will be responsible for both the preoperative administration of antibodies to allograft recipients and the daily assessment of mouse allograft to determine survival rates. Project 4) David Ginsburg, M.D., Division of Medical Genetics, Department of Internal Medicine and Department of Human Genetics: Identifying Thrombosis Modifier Genes and Novel Anticoagulants in Zebra fish. Core A will directly collaborate with Dr. Ginsburg (Project 4) and coordinate specific Core A interactions with Co-Pi Dr. David Sherman of the Center for Chemical Genomics (CCG) to develop high throughput chemical screens to identify novel anticoagulants in zebrafish (Danio rerio) These screens will focus on lipid disorders and vascular disease with the goal of providing novel drug therapies to treat human disorders of hemostasis. It is intended that Core A will be a central part of the PPG Program and will benefit all investigators involved.
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