Blood vessel formation in cancer and development; use mouse culture (stem cell derived vessels) and in vivo models (embryos and tumors); genetic, cell and molecular biological tools; how do vessels assemble and pattern?, dynamic image analysis.
Research interests include atherosclerosis, thrombosis and von Willebrand's disease. The role of von Willebrand factor in arterial thrombosis is being studied in atherosclerotic vessels to gain a better understanding of thrombosis and its possible prevention in people with coronary artery disease. Comparative pathology and the use of animal models in research are also the focus of some research efforts.
Cell adhesion, both to other cells and to ECM, signaling, the cytoskeleton and cell migration. The Rho family of GTPases, their regulation by guanine nucleotide exchange factors and GAPs. Inflammation and leukocyte transendothelial migration.
Gene targeting and state-of-the-art phenotyping methods are used to elucidate the reproductive and cardiovascular roles of the adrenomedullin system and to characterize the novel GPCR-signaling mechanism of Adm’s receptor and RAMP’s.
Our research centers on the cell biology and biochemistry of motor proteins and the cytoskeleton and their roles in processes such as cell crawling, phagocytosis, organelle transport.
Our research is concerned with proteases and their inhibitors in various disease processes (thrombosis and cancer); our science tools are structure-activity, cell biology and signaling, pathobiology, immunohistochemistry, and in vivo models.
1) Identification of critical elements of human genetic variability contributing to pain sensitivity and pathophysiological pain states, 2) identification of therapeutic targets for pain management, 3) studying molecular hierarchy of functional SNPs commonly present in human population and 4) studying the molecular mechanisms of gene expression regulation.
We are interested in how complex signaling systems interact to preserve homeostasis, while also optimizing the response of the organism to environmental changes. Two different projects are ongoing in the laboratory: Project 1: Matching renal salt excretion with dietary salt intake is vital for survival. We are integrating whole animal physiological studies and innovative molecular techniques to investigate the role of a new intestinal hormone, uroguanylin, in this process. Project 2: How do target organs communicate with neural circuits? We are investigating feedback regulation of a simple neural circuit that uses a novel form of muscle-to-nerve communication to control the contractions of the heart musculature.
Our research focuses on understanding the molecular and cellular mechanisms of leukocyte (white blood cell) trafficking and homing in vascular inflammation and immune responses. We are interested in the glycobiology of the Selectin leukocyte adhesion molecules and their ligands, and understanding the roles for these glycoproteins in the pathogenesis of inflammatory/immune cardiovascular diseases such as atherosclerosis and vasculitis. We are also interested in the mechanisms whereby the selectins and their ligands link the inflammatory response and coagulation cascade and thereby modulate thrombosis and hemostasis.
We are studying how hemangioblasts, a bipotential precursor of endothelial and hematopoietic lineages, are specified and differentiated during development using zebrafish as a model system.
The regulatory role of platelet membrane phosphatidylserine in blood coagulation; mechanism of protein-mediated membrane fusion in secretory processes and virus infection. Director of the Molecular & Cellular Biophysics Training Program.
We study the blood clotting protein fibrinogen, its biochemistry and its role in disease (Curr Opin Hematol. 14:236, 2007). We synthesize variant fibrinogens to correlate structure and function using crystallographic and biochemical analyses (Biochemistry 46:5114, 2007). We examine the mechnical properties of fibrin fibers using atomic force microscopy (Science 313:634. 2006). We explore the interactions of fibrinogen with biomaterials (Acta Biomaterialia 3:663, 2007). We use patient samples and mouse models to examine the links between fibrinogen and disease (J Thromb Haemost. 2:1484, 2004). Member of the Molecular & Cellular Biophysics Training Program.
My research goals are to identify the mechanisms by which environmental factors regulate smooth muscle cell phenotype and to define the transcriptional pathways that regulate SMC-specific gene expression.
Our research is focused on the genetics and molecular pathology of complex multi-factorial conditions in humans - obesity, diabetes, hypercholesterolemia, insulin resistance, and hypertension. These conditions underlie cardiovascular diseases, including atherosclerosis, the major cause of death and disabilities in North America. Our approach consists of experiments with mice carrying modifications in various genes important for the maintenance of vascular function, antioxidant defense, and metabolism. We dissect how gene-gene and gene-environment interaction influences the pathogenesis of these common human conditions and their
complications.
The goal of the laboratory’s research is to define the structure and function of an intracellular Ca2+ release channel in skeletal and cardiac muscle, using molecular biological and electrophysiological methods and by creating mutant mice.
Mechanisms by which cells control their shape via modulation of the actin cytoskeleton. Palladin, a novel cytoskeletal protein, may be involved in organizing the actin cytoskeleton as a scaffolding protein and may contribute to changes in cell shape.
The goal of our research is to identify signaling mechanisms that contribute to normal and pathophysiological cell growth in the cardiovascular system. We study cardiac and vascular development as well as heart failure and atherosclerosis.
Blood Flow and Endothelial Cell Function. We are interested in how vascular endothelial cells signal and respond to blood flow in the context of cardiovascular disease and tumor progression.
We investigate the role of cardiac specific proteins (Muscle Ring Finger or MuRF proteins) that regulate glucose and fatty acid metabolism, cardiac muscle mass, and sarcomere protein metabolism in the context of common cardiac diseases. Recently, we have identified that MuRF proteins have ubiquitin ligase activity, which enables them to interact with specific proteins, post-translationally modify them with ubiquitin, and subsequently target them for degradation. We focus on mouse models of disease using transgenic and knock-out mice, integrating cardiac physiology with several imaging modalities including echocardiography, Doppler, and SPECT. Since several of the models we have created involve developmental defects, we investigate in utero cardiac function and signaling pathways
with this state of the art of imaging. Our overall goal is to determine how the ubiquitin proteasome system specifically regulates the heart at the molecular level and determine how this affects cardiac function, in order to
translate these findings into therapies & diagnostics for common cardiac diseases such as heart failure and myocardial infarction.
Cellular, molecular, and biochemical mechanisms of blood coagulation; Relationships between cells (monocytes, fibroblasts, endothelial cells, smooth muscle cells, platelets and others), plasma protein concentration, thrombin generation and blood clots; Fibrin formation, structure and stability; Mechanical properties of fibrin; Disorders associated with bleeding and thrombosis, including hemophilia and cardiovascular disease (heart attack, stroke, deep vein thrombosis, pulmonary embolism); Preclinical testing of hemostatic and antithrombotic drugs
