An important goal of the Cardiac Bioelectricity and Arrhythmia Center (CBAC), Washington University in St. Louis is to enhance and promote education and training in biomedical engineering, life sciences, and clinical medicine. The CBAC hosts seminars each semester, where world renowned clinicians and researchers are invited to lecture. These seminars are attended by engineering, physics and medical school faculty and graduate students, as well as professionals from outside the university. These seminar videos are open to the general public.
Disclaimer: All material within each video file was filmed during a Cardiac Bioelectricity and Arrhythmia Center (CBAC) seminar at Washington University in St. Louis. It was made available on this website with permission from the speaker, who reserves and holds all rights. The video files are for educational purposes only and may not be reproduced, distributed or copied in any format.
Videos will load in an external platform. For full screen viewing, click on the bottom right corner of the video screen.
For more information about the seminars, please contact Huyen (Gwen) Nguyen at hbnguyen@wustl.edu
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ECGI Al in 2019: The Power to See the Invisible
David E. Albert M.D.
11-25-2019
Computerized interpretation has been standard in 12-Lead ECG machines & patient monitors for nearly 50 years! So what is all this "Al for ECG" hype? Traditional computerized ECG analysis told us what experts, could see! Dr. Albert's presentation will cover the NEW era of computerized ECG analysis based on machine learning and Deep Neural Networks, as these tools engage the detection of conditions and pathologies that experts cannot see!
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From Biological Pacemakers to Cancer Therapy
Ira S. Cohen M.D., Ph.D.
10-28-2019
Biological Pacemakers that can respond to the autonomic nervous system could be an improvement over electronic pacemakers. The current seminar will briefly review a cell-based approach to creating a biological pacemaker using human Mesenchymal Stem Cells (hMSCs) as a means of delivery for the HCN2 gene to the canine ventricle. In order to achieve this goal, it was necessary to demonstrate that hMSCs make connexins and could form gap junctions. Once gap junction formation was demonstrated, it became possible to think of hMSCs as a delivery cell for other payloads. SiRNA is a short oligonucleotide that can silence the expression ...Read More
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Structural Dynamics of Voltage-Gated Ion Channels: Implications for Health & Disease
Lucie Delemotte Ph.D.
2-25-2019
Voltage-gated ion channels are the membrane proteins whose opening and closing are responsible for the propagation of action potential in excitable cells. Their dysfunction leads to diseases such as cardiac arrhythmias, epilepsy or muscle ataxia. As such, they constitute major drug targets.
Voltage-sensitive ion channels function depends in a large part on their structure, and high-resolution structures of prototype channels have been known since the early 2000s. Nevertheless, we still lack a detailed understanding of their dynamic behavior as well as the structural ensemble that make up their functional cycle. Both of these aspects are critical for designing innovative and ...Read More
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In silico Approaches to Inform Atrial Fibrillation Selective Pharmacotherapy
Eleonora Grandi Ph.D.
4-29-2019
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Human iPSC-based Engineered Micro-Tissues to Study Familial Cardiomyopathy
Nathan Huebsch Ph.D.
4-15-2019
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Structural Mechanisms of Selectivity and Gating of Mitochondrial Calcium Uniporter
Youxing Jiang Ph.D.
11-4-2019
Mitochondria can take up large amounts of Ca2+ from their environment, a process that can modulate ATP production, alter cytoplasmic Ca2+ dynamics, and trigger cell death. Ca2+ enters the mitochondrial matrix through the mitrochondrial calcium uniporter, a highly selective Ca2+ channel that is localized to the inner mitochondrial membrane. In humans, the uniporter is a protein complex or uniplex consisting of at least four components: the ion conducting pore MCU, the essential membrane spanning subunit EMRE, and the Ca2+-sensing gate-keeping proteins MICU1 and MICU2. While MCU is found in all major eukaryotic taxa, EMRE is metazoan-specific and is required for ...Read More
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Unravelling the Mechanisms of Fight or Flight: It's All About the Neighborhood
Steven O. Marx M.D.
9-16-2019
Increased cardiac contractility during fight-or-flight response is caused by ß-adrenergic augmentation of the cardiac Cav1.2 channels. It is assumed that this iconic regulation involves phosphorylation of Cav1.2 α1C/ß-subunits. In transgenic murine hearts expressing fully PKA phosphorylation-deficient mutant α1C/ß subunits, this regulation persists, however, suggesting involvement of extra-channel factors. I will discuss our recent studies using perioxidase-catalyzed labeling in mice hearts expressing ascorbate peroxidase conjugated- α1C or ß2B with multiplexed quantitative proteomics, which allowed traacking of thousands of proteins in proximity of Cav1.2. I will discuss how the Cav1.2 micro-environment is altered upon ß-adrenergic stimulation, and how this alteration in the ...Read More
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Ventricular Tachycardia Following Myocardial Infarction: What is the Substrate?
Alfred E. Buxton M.D.
2-5-2018
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Treatment of Ventricular Arrhythmias in Structural Heart Disease
David J. Callans M.D., F.H.R.S.
4-16-2018
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Bifurcation Theory and Cardiac Arrhythmias
Alan Garfinkel Ph.D
1-29-2018
Mathematical models of cardiac arrhythmias come in two distinct forms. High-dimensional, biophysically detailed models give us realism; they talk about biophysical quantities that can be experimentally and clinically altered.
But there is another critical kind of modeling: Low-dimensional modeling tries to isolate the essential dynamical phenomena responsible for a qualitative outcome. It gives us deeper insights into causal mechanisms. The most important technique of low-dimensional modeling is bifurcation theory. A bifurcation is a qualitative change in the solution to a differential equation, as a key parameter is varied. Identification of these key parameters then becomes the central task, because it ...Read More
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Ryanodine Receptor: Structure, Function, & Therapeutic Targeting for Diseases of Heart & Muscle
Andrew R. Marks M.D.
11-12-2018
Ryanodine receptor (RyR) channels are required for release of calcium from intracellular stores, aprocess essential for many cellular functions including excitation-contraction (EC) coupling in skeletal and cardiac muscle, and hormone and neurotransmitter release. They are the largest ion channels, comprised of the four identical -565 kDa channel-forming protomers, as well as regulatory subunits, enzymes and their respective targeting/anchoring proteins, in a macromolecular complex that exceeds three million daltons. We have obtained high-resolution cryo-electron microscopy (Cryo-EM) reconstructions from highly purified rabbit skeletal muscle RyR1 in the open and closed states. Our data reveal that RyRs are members of the six transmembrane ...Read More
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L-Type Calcium Channel Gating Modifiers: Prospective Next-Generation Antiarrhythmics
Riccardo Olcese Ph.D.
12-3-2018
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Advancements in Implantable Cardioverter Defibrillator Therapy: Focus on Lead Technology and Defibrillation
Andrea M. Russo M.D., F.A.C.C., F.H.R.S.
11-5-2018
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Using Genetics to Identify the Molecular Mechanisms of Atrial Fibrillation
Patrick T. Elinor M.D., Ph.D
12-18-2017
Atrial fibrillation (AF) affects over 3 million individuals in the US and 4.5 million individuals in Europe. In addition, AF is associated with an increased risk of stroke, dementia, heart failure, death and health care costs. Many AF risk factors have been identified including aging, cardiovascular disease, and family history. Although heritable forms of AF were previously considered rare, we have established evidence of substantial AF heritability over the last decade. Genome-wide association studies (GWAS) provide a powerful tool to identify common variants underlying disease risk. In 2007 a GWAS for AF identified a locus on chromosome 4q25. Later that ...Read More
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Massively-Parallel All-Optical Cardiac Electrophysiology
Emilia Entcheva Ph.D.
4-17-2017
Optical targeting (stimulation or recording) allows distributed parallel access to thousands and even millions of cells and locations at the same time, and within the tissue setting; optical targeting is high-throughput by nature. In this talk, I will discuss and demonstrate the combination of optogenetic stimulation with optical imaging of electrical activity in cardiomyocytes, i.e. the realization of “all-optical electrophysiology” in a high-throughput manner (HTS). Examples will include demonstration of cardiac “wave steering” by light and the use of a new fully-automated all-optical HTS platform (OptoDyCE) for drug screening using patient-derived cardiomyocytes (iPS-CMs).
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Novel Regulators of Cardiac Rhythm
Glenn I. Fishman M.D., F.A.C.C., F.A.H.A., F.A.C.P., F.H.R.S
12-4-2017
Our laboratory has been interested in multiple facets of cardiac electrophysiology and arrhythmia mechanisms, with a particular focus on identifying novel regulators of cardiac excitability, impulse propagation, and arrhythmia susceptibility. Our most recent studies seek to decipher the mechanisms responsible for specification, maturation and function of the specialized cardiac conduction system and identifying novel transcriptional regulators that influence cardiomyocyte electrophysiological diversity and integrated cardiac excitability. I will describe the role of two novel transcription factors (one recently reported and the second still a work in progress) that appear to play critical roles in establishing functional diversity throughout individual compartments of ...Read More
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Membrane-mediated Alterations in Cardiac Bioenergetics, Electrophysiology & Signaling
Richard W. Gross M.D., Ph.D
11-27-2017
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Lessons Learned from Mapping & Ablation of Nonischemic Cardiomyopathy
Francis E. Marchlinski M.D.
11-20-2017
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Cardiac Mechanoelectric Feedback: A Role for Caveolae?
Andrew D. McCulloch Ph.D.
1-18-2017
Mechanical stretch of cardiac muscle affects myocyte electrophysiology is potentially arrhythmogenic. We investigated the effects of stretch in vitro and in the intact heart on action potential conduction. Using optical mapping to measure in isolated mouse hearts and in micropatterned mouse cardiomyocyte we found that conduction velocity decreased rapidly and reversibly with volume loading and stretch. This slowing was not altered by stretch-activated channel inhibition, but was abrogated when caveolae were disrupted by genetic deletion of caveolin-3 or chemical depletion of membrane cholesterol. Electron microscopy showed that stretch in wild-type mouse hearts, causes recruitment of caveolae to the sarcolemma. Stretch ...Read More
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Defining New Pathways Underlying Human Arrhythmia
Peter J. Mohler Ph.D.
3-6-2017
Our research is focused on the mechanisms underlying the targeting and regulation of membrane-associated (ion channels, transporters, receptors) and signaling proteins in cardiac and other excitable cells. In particular, we are interested in the role of membrane-associated ankyrin and spectrin family of polypeptides in the targeting and function of ion channels and transporters as well as kinases and phosphatases. A primary focus of the lab is the role of the ankyrin-G-based pathway for targeting voltage gated sodium channels to the intercalated disc of cardiomyocytes. We have discovered a direct requirement of ankyrin-G for Na channel targeting and have linked human ...Read More
