The Anumonwo laboratory studies the properties of an ion channel, which depends on its three-dimensional structure as well as on the interactions of the channel protein with other (accessory) proteins in specific micro-domains of the cell. A number of cardiac rhythm disturbances have been associated with mutant ion channel proteins, accessory proteins to the ion channels, or the improper interactions between the two proteins. Research in our laboratory focuses on understanding the molecular interactions of cardiac ion channel proteins under normal and pathophysiologial conditions. We use a combination of electrophysiological, biochemical and molecular biological techniques to carry out these investigations.
The Beard and Carlson lab (cooperating with Brian Carlson) is focused on systems engineering approaches for understanding the biophysical and biochemical operation of physiological systems. Dan Beard is the Director of the Virtual Physiological Rat (VPR) project, previously supported as an NIH National Center for Systems Biology, working to analyze, interpret, simulate, and ultimately predict physiological function in health and disease. The scope of topics in the lab cover integrated experimental and computational projects spanning the scales of subcellular to whole organism function and include: (1) Cardiac energy metabolism. (2) Cardiovascular system dynamics. (3) Regulation of coronary blood flow. (4) Stem cell derived cardiomyocytes.
Our research focuses on mechanisms of wave propagation and fibrillation using a combination of experimental, clinical, and numerical approaches with the aim of better understanding of acute and chronic atrial fibrillation as well as ventricular fibrillation. Current projects in Dr. Berenfeld's laboratory include:1. Dynamics of Impulse Propagation and Reentrant Activity.2. Mechanisms of Atrial Fibrillation. 3. Mapping of Cardiac Fibrillation. 4. Biophysical Mechanisms in Two Inherited Cardiac Diseases.
Research Associate Professor, Molecular & Integrative Physiology
The Beard and Carlson lab (cooperating with Daniel Beard) is focused on systems engineering approaches for understanding the biophysical and biochemical operation of physiological systems. Dan Beard is the Director of the Virtual Physiological Rat (VPR) project, previously supported as an NIH National Center for Systems Biology, working to analyze, interpret, simulate, and ultimately predict physiological function in health and disease. The scope of topics in the lab cover integrated experimental and computational projects spanning the scales of subcellular to whole organism function and include: (1) Cardiac energy metabolism. (2) Cardiovascular system dynamics. (3) Regulation of coronary blood flow. (4) Stem cell derived cardiomyocytes.
The long-term goal of Dr. Chen's laboratory is to stimulate bench-to-bedside research that sheds light on molecular mechanisms underlying the development and progression of diabetes-induced cardiovascular diseases (CVD). Discoveries from innovative and multi-disciplinary projects will reveal novel and effective intervention strategies to prevent and treat diabetes and CVD. In the past 15 years, Dr. Chen's laboratory has made a series of significant contributions to our understanding of the role of PPARgamma activation as a determinant of vascular cell gene expression and cellular function and has been among the first to begin to define the role of PPARdelta activation in the cardiovascular system. In addition, the discovery of the high affinity physiological PPARgamma ligands, nitroalkene derivatives of linoleic acid (LNO2) and oleic acid (OA-NO2), advances our understanding of endogenous PPARgamma modulation and provides novel therapeutic strategies for treating diabetes and CVD.
The Isom laboratory focuses on understanding the molecular composition of individual sodium channel signaling complexes in excitable cells. We are testing the hypothesis that studying the conducting and non-conducting functions of the sodium channel beta subunits may yield important insights into the molecular basis of inherited disease. Part of our studies involve disruption of sodium channel signaling complexes in vivo and testing the consequences of such disruption on paroxysmal diseases such as cardiac arrhythmia and epilepsy. In addition, because sodium channel beta subunits can function as cell adhesion molecules in the absence of the ion conducting pore, we are studying whether mutations in beta subunit genes may result in defects in axon guidance or cell-cell communication. Our studies have significant clinical implications since it is already known that mutations in ion channels and their auxiliary subunits can lead to neurological or cardiovascular diseases.
The Michele laboratory focuses on the mechanisms of muscular dystrophy and cardiomyopathies associated with mutations in the transmembrane dystrophin-glycoprotein complex and abnormal glycosylation of the central protein in this complex, dystroglycan. The cellular mechanism of dystroglycan modification, and the resulting pathways leading to muscular dystrophy and cardiomyopathy are currently unclear. Our laboratory is currently exploring these mechanisms using spontaneous mutant, traditional and conditional targeted mouse models in vivo, and studying the effects on skeletal muscle function and cardiac myocyte biology in vitro.
Dr. Michele is NOT accepting fellows for Summer 2023.
The Russell Laboratory examines the genetic determinants of heart development and the pathogenesis of human congenital heart defects. Using a zebrafish model, we are characterizing novel signaling pathways determined to be involved in cardiac outflow tract development based on the identification of genetic mutations in human patients with tetralogy of Fallot and hypoplastic left heart syndrome. In addition, we are continuing to search for additional novel disease genes using massively parallel sequencing of human patient samples.
Henry and Mala Dorfman Family Professor of Pediatric Hematology/Oncology
In the Shavit laboratory we perform “clinically directed basic research” in the field of hemostatic and thrombotic disorders. Patients with deficiencies of particular blood coagulation factors are often labeled with bleeding or clotting disorders, yet often have no phenotype. On the other hand there are patients with phenotypes out of proportion to their laboratory clotting factor profile. Thus we are often unable to predict an individual patient's risk with any useful degree of accuracy. Our goal is the identification of genes that modify blood clotting factors and their phenotypic expression. Knowledge of such modifier genes will improve diagnosis and classification of blood coagulation disorders, identify potential targets for therapy, and further our understanding of the underlying biology of hemostasis and thrombosis. In order to achieve these goals, we are developing zebrafish models of human blood clotting disorders.
Associate Professor, Cardiac Surgery
Associate Professor, Molecular & Integrative Physiology
The Westfall laboratory focuses on understanding myofilament function and its modulation by signaling cascades during health and disease. Ongoing studies are focused on 1) understanding the role of the third troponin I cluster in modulating contractile function, 2) evaluating whether there is an additive or synergistic effect of the 3 clusters on relaxation, 3) determining whether mutations within the regulatory portions of troponin I influence the phosphorylation response, and 4) investigating the role of these troponin I phosphorylation sites on contractile function under pathophysiological conditions and using gene transfer into myocytes from explanted failing human hearts to determine whether phosphomimetic troponin I mutants improve contractile performance.
Dr. Westfall is NOT accepting fellows for Summer 2023.