Yoram Rudy , Ph.D., F.A.H.A., F.H.R.S.
(Case Western Reserve University, 1978); The Fred Saigh Distinguished Professor of Engineering; Professor of Biomedical Engineering, Cell Biology & Physiology, Medicine, Radiology, and Pediatrics; Director of the Cardiac Bioelectricity and Arrhythmia Center (CBAC)

Research Interests:
Our research aims at understanding the mechanisms that underlie normal and abnormal rhythms of the heart at various levels, from the molecular (ion channel) and cellular to the whole heart. We are also developing a novel noninvasive imaging modality (Electrocardiographic Imaging, ECGI) for the diagnosis and guided therapy of cardiac arrhythmias. Through the development of detailed mathematical models of cardiac cells and tissue, we are investigating the mechanisms and consequences of genetically-inherited cardiac arrhythmias, impaired cell-to-cell communication, and abnormal spread of the cardiac impulse in the diseased heart (e.g. myocardial infarction). ECGI imaging is currently being tested, evaluated and applied in patients with various heart conditions.

Websites:
http://rudylab.wustl.edu
http://cbac.wustl.edu

Representative Research Figures:

Cardiac cell model		Activation isochrones during reentry		ECGI mapping system (torso vest)

Richard W. Gross, M.D., Ph.D.
(New York University Medical School, 1976; Cardiology Fellow, Barnes Hospital, St. Louis, 1978-81; Washington University, St. Louis, Ph.D., 1982); Professor of Medicine, Chemistry, and Molecular Biology & Pharmacology; Director, Division of Bioorganic Chemistry and Molecular Pharmacology (Joint Appointment with the School of Medicine), Department of Internal Medicine, Department of Molecular Biology and Pharmacology and Department of Chemistry, Washington University School of Medicine

Research Interests:
Our research is focused on the chemical biology of membranes in health and disease. Biologic membranes are comprised of a structurally diverse array of thousands of distinct chemical entities in a bilayer configuration that are in constant motion providing a rich repertoire of chemical forces that can be used to modulate the conformation and function of transmembrane proteins such as ion channels and ion pumps. Through adaptation of a bilayer structure membranes serve as a hydrophobic scaffold for the organization of complex supramolecular chemical assemblies that are used in biologic systems as signaling platforms.

Website:
http://chemistry.wustl.edu

Representative Research Figures:

Patrick Y. Jay, M.D., Ph.D.
(Washington University, 1995); Assistant Professor of Pediatrics and Genetics

Research Interests:
Function of the cardiac transcription factor Nkx2-5 in the development of the cardiac conduction system and heart.  Role of Nkx2-5 in the pathogenesis of postnatal conduction defects and cardiomyopathy.  Genomic analysis of cardiac gene expression.
Clinical Interests:
Pediatric cardiologist, St. Louis Children's Hospital.

Website:
not listed

Representative Research Figures:
None at this time.

Jean E. Schaffer, M.D.
(Harvard Medical School, 1986); Associate Professor of Medicine, Molecular Biology & Pharmacology

Research Interests:
While fatty acids are critical for many cellular functions, accumulation of excess fatty acids in non-adipose tissues leads to cell dysfunction and/or cell death. This lipotoxicity plays an important role in the pathogenesis of diabetes and heart failure. We are using genetic approaches to identify molecules that are important for channeling imported long chain fatty acids to specific cell fates, and to identify lipid metabolic and signaling pathways critical for fatty acid-induced apoptosis. Specifically, we have used a promoter trapping strategy to isolate mutant cell lines resistant to fatty acid-induced apoptosis. We are presently characterizing the disrupted gene that confers resistance in each mutant. We have also created transgenic mouse lines with tissue-restricted overexpression of proteins that facilitate fatty acid transport to understand the physiology of lipotoxicity. Our studies may provide insight to the pathogenesis of human disorders such as obesity, diabetes, and heart failure, in which fatty acid homeostasis is perturbed.

Website:
http://ccr.im.wustl.edu/faculty/JESchaffer/Schaffer.htm

Representative Research Figures:

Rhodamine-phallodin cytochemical staining and fluorescence microscopy of wild type CHO cells supplemented with excess palmitic acid for 5 hours demonstrates marked abnormalities of cytoskeletal structure.		Under conditions of fatty acid (FA) overload in non-adipose tissues, the cellular capacity to store FAs as triglycerides or to use FAs for energy is overwhelmed. This FFA overload can lead to the production of ROS, which can, in turn, induce ER stress. Prolonged or severe ER stress can lead to further ROS accumulation, potenitally amplifying the apoptotic/cell death response. Palmitoyl CoA, generated by esterification of palmitar as it enters the cell, may also induce ER stress directly, leading to the production and accumulation of ROS and subsequent apoptosis/ cell death. In either of these scenarios, the eukaryotic elongation factor, eEF1A-1, mediates actin cytoskeleton changes invloved in the execution of the lipotoxic cell death response downstream of induction of oxidative and ER stress.		Using a cardiac selective promoter, we generated transgenic (Tg) mice with cardiac overexpression of the fatty acid transport protein 1 (FATP). These mice have 4-fold increase in cardiac fatty acid uptake, 2-fold increase in cardiac fatty acid oxidation, and 2-fold increase in cardiac free fatty acid content. Two-dimensional guided M-mode echocardiographic images (A,B) and trans-mitral blood flow (C,D) from 3-month-old wild type (WT: A,C) and Tg (B,D) mice demonstrate normal systolic function but from a non-compliant pattern of left ventricular diastolic filling. Tg mice have QT current densities measured in isolated left ventricular (LV) myocytes (F).