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Research in the Anderson laboratory focuses on cellular signaling and ionic mechanisms that cause heart failure, arrhythmias and sudden cardiac death, major public health problems worldwide. Primary focus is on the multifunctional Ca2+ and calmodulin-dependent protein kinase II (CaMKII). The laboratory identified CaMKII as an important pro-arrhythmic and pro-cardiomyopathic signal, and its studies have provided proof of concept evidence motivating active efforts in biotech and the pharmaceutical industry to develop therapeutic CaMKII inhibitory drugs to treat heart failure and arrhythmias.
Under physiological conditions, CaMKII is important for excitation-contraction coupling and fight or flight increases in heart rate. However, myocardial CaMKII is excessively activated during disease conditions where it contributes to loss of intracellular Ca2+ homeostasis, membrane hyperexcitability, premature cell death, and hypertrophic and inflammatory transcription. These downstream targets a...ppear to contribute coordinately and decisively to heart failure and arrhythmias. Recently, researchers developed evidence that CaMKII also participates in asthma.
Efforts at the laboratory, funded by grants from the National Institutes of Health, are highly collaborative and involve undergraduate assistants, graduate students, postdoctoral fellows and faculty. Key areas of focus are:
• Ion channel biology and arrhythmias
• Cardiac pacemaker physiology and disease
• Molecular physiology of CaMKII
• Myocardial and mitochondrial metabolism
• CaMKII and reactive oxygen species in asthma
Mark Anderson, MD, is the William Osler Professor of Medicine, the director of the Department of Medicine in the Johns Hopkins University School of Medicine and physician-in-chief of The Johns Hopkins Hospital. view more
We specialize in unconventional, multi-disciplinary approaches to studying the heart at the intersection of applied mathematics, physics and computer science. We focus on theory development that leads to new technology and value delivery to the society. Currently we have three research programs:
1. Precision Medicine
To develop a quantitative approach to personalized risk assessment for stroke and dementia based on patent-specific heart anatomy, function and blood flow.
Disciplines: Cardiac Hemodynamics; Medical Imaging Physics; Continuum Mechanics; Computational Fluid Dynamics
2. Information Theory
To quantify and perturb cardiac fibrillation that emerges as a macro-scale behavior of the heart from micro-scale behaviors of inter-dependent components.
Disciplines: Cardiac Electrophysiology; Spiral Wave; Information Theory; Complex Networks
3. Artificial Intelligence
To develop artificial intelligence algorithms to predict the future risk of heart attack, stroke and sudden... death, and to assist surgical interventions to prevent these outcomes.
Disciplines: Medical Imaging Physics; Artificial Intelligence; Robotically Assisted Interventions
The main focus of the Becker lab has been on the mechanisms and consequences of post-ischemic myocardial inflammation.
Genomic control of platelet function:
Aggregation of blood platelets initiates clotting in coronary arteries, the main cause of heart attacks. Our laboratory conducts experiments to understand how genes control platelet function. Through funding by the National Heart Lung and Blood Institute, we have performed candidate gene analysis, linkage studies, whole genome association studies, and now whole genome sequencing in about 2000 healthy subjects from families with early onset coronary artery disease. The subjects are siblings or offspring of an individual identified with coronary artery disease before age 60 in the GeneSTAR Research Program (Genetic Studies of Atherosclerosis Risk). We have identified a large number of common and rare genetic variants associated with platelet aggregation, and although some variants are located in genes known to be important in... the biology of platelet function, most are in non-protein coding regions of genes (introns) or in intergenic regions of the genome. To understand better how these variants influence platelet function, we created pluripotent stem cells from blood mononuclear cells in 257 genotyped GeneSTAR subjects and then transformed the stem cells to megakaryocytes, the source of platelets in the bone marrow. We have determined the entire transcriptome of these megakaryocytes to measure gene expression levels in an effort to functionally link genetic variation with platelet function. We are also interested in epigenetic effects which regulate the amount of gene transcription and resulting protein formation. We have done similar transcriptomic and proteomic studies in blood platelets as we have in stem cell-derived megakaryocytes.
Our goal is to identify new therapeutic targets for drug development to control excessive platelet aggregation and reduce the risk of heart attack in susceptible individuals. We also hope to use the genetic information to predict who is at greatest risk for platelet aggregation or bleeding, and tailor treatment to effectively apply individualized precision medicine.
The Becker laboratory also extends its cardiovascular work well beyond platelet function, as noted on the GeneSTAR Research Program website. view more
The Cammarato Lab is located in the Division of Cardiology in the Department of Medicine at the Johns Hopkins University School of Medicine. We are interested in basic mechanisms of striated muscle biology.
We employ an array of imaging techniques to study “structural physiology” of cardiac and skeletal muscle. Drosophila melanogaster, the fruit fly, expresses both forms of striated muscle and benefits greatly from powerful genetic tools. We investigate conserved myopathic (muscle disease) processes and perform hierarchical and integrative analysis of muscle function from the level of single molecules and macromolecular complexes through the level of the tissue itself.
Anthony Ross Cammarato, MD, is an assistant professor of medicine in the Cardiology Department. He studies the identification and manipulation of age- and mutation-dependent modifiers of cardiac function, hierarchical modeling and imaging of contractile machinery, integrative analysis of striated muscle performan...ce and myopathic processes. view more
Founded in 1942 by surgeon Alfred Blalock and surgical technician Vivien Thomas, the Cardiac Surgery Research Lab at The Johns Hopkins Hospital serves not only to spearhead discovery and innovation in cardiothoracic surgery, but also to train future leaders in the field. Active areas of investigation include the development of novel, nanoparticle-based therapeutics to mitigate acute lung injury, avoid neurological injury during cardiac surgery, and improve organ preservation during heart and lung transplantation. The lab is also active in a variety of clinical research projects aimed at improving outcomes for our patients.
Equally important, the lab plays a critical role in training residents for impactful careers in academic cardiothoracic surgery. Medical students, residents, and fellows receive hands-on simulation experiences to hone surgical skills outside of the operating room. The lab also serves as a training ground to develop research and investigation skills as trainees lea...rn methods of advanced statistical analysis and academic writing. Special programs for undergraduates and medical students help develop their passion for cardiac surgery and surgical research, giving unique opportunities to young talent.
William A. Baumgartner, MD, serves on the cardiac surgery faculty as the Vincent L. Gott Professor and Director of the Cardiac Surgical Research Laboratory. view more
The Cardiology Bioengineering Laboratory, located in the Johns Hopkins Hospital, focuses on the applications of advanced imaging techniques for arrhythmia management. The primary limitation of current fluoroscopy-guided techniques for ablation of cardiac arrhythmia is the inability to visualize soft tissues and 3-dimensional anatomic relationships.
Implementation of alternative advanced modalities has the potential to improve complex ablation procedures by guiding catheter placement, visualizing abnormal scar tissue, reducing procedural time devoted to mapping, and eliminating patient and operator exposure to radiation.
Active projects include
• Physiological differences between isolated hearts in ventricular fibrillation and pulseless electrical activity
• Successful ablation sites in ischemic ventricular tachycardia in a porcine model and the correlation to magnetic resonance imaging (MRI)
• MRI-guided radiofrequency ablation of canine atrial fibrillation, and ...diagnosis and intervention for arrhythmias
• Physiological and metabolic effects of interruptions in chest compressions during cardiopulmonary resuscitation
Henry Halperin, MD, is co-director of the Johns Hopkins Imaging Institute of Excellence and a
professor of medicine, radiology and biomedical engineering. Menekhem M. Zviman, PhD is the laboratory manager.
The CRCIF was established to foster collaborative efforts aimed at elucidating the role of intermediate filaments (IFs) in the heart. Intermediate filaments constitute a class of cytoskeletal proteins in metazoan cells, however, different from actin microfilaments and tubulin microtubules, their function in cardiac cells is poorly understood. Unique from the other two components of the cytoskeleton, IFs are formed by cell type-specific proteins. Desmin is the main component of the IFs in the cardiac myocytes. We measured the consistent induction of desmin post-translational modifications (PTMs, such as phosphorylation, etc.) in various clinical and experimental models of heart failure. Therefore, one of our main focuses is to determine the contribution of desmin PTMs to the development of heart failure in different animal and clinical models.
• Quantification of desmin PTM-forms in different forms of heart failure at the peptide level using mass spectrometry
• F...unctional assessment of the role of desmin PTMs in heart failure development using single site mutagenesis and biophysical methods
• Molecular characterization of desmin preamyloid oligomers using mass spectrometry, in vitro and in vivo imaging
• Assessment of the diagnostic and pharmacological value of desmin PTMs in heart failure development view more
The C. Kwon Lab studies the cellular and molecular mechanisms governing heart generation and regeneration.
The limited regenerative capacity of the heart is a major factor in morbidity and mortality rates: Heart malformation is the most frequent form of human birth defects, and cardiovascular disease is the leading cause of death worldwide. Cardiovascular progenitor cells hold tremendous therapeutic potential due to their unique ability to expand and differentiate into various heart cell types.
Our laboratory seeks to understand the fundamental biology and regenerative potential of multi-potent cardiac progenitor cells – building blocks used to form the heart during fetal development — by deciphering the molecular and cellular mechanisms that control their induction, maintenance, and differentiation. We are also interested in elucidating the maturation event of heart muscle cells, an essential process to generate adult cardiomyocytes, which occurs after terminal differentiation ...of the progenitor cells. We believe this knowledge will contribute to our understanding of congenital and adult heart disease and be instrumental for stem cell-based heart regeneration.
We have developed several novel approaches to deconstruct the mechanisms, including the use of animal models and pluripotent stem cell systems. We expect this knowledge will help us better understand heart disease and will be instrumental for stem-cell-based disease modeling and interventions for of heart repair.
Dr. Chulan Kwon is an assistant professor of medicine at the Johns Hopkins University Heart and Vascular Institute. view more
The Foster Lab uses the tools of protein biochemistry and proteomics to tackle fundamental problems in the fields of cardiac preconditioning and heart failure. Protein networks are perturbed in heart disease in a manner that correlates only weakly with changes in mRNA transcripts. Moreover, proteomic techniques afford the systematic assessment of post-translational modifications that regulate the activity of proteins responsible for every aspect of heart function from electrical excitation to contraction and metabolism. Understanding the status of protein networks in the diseased state is, therefore, key to discovering new therapies.
D. Brian Foster, Ph.D., is an assistant professor of medicine in the division of cardiology, and serves as Director of the Laboratory of Cardiovascular Biochemistry at the Johns Hopkins University School of Medicine.
Our group is interested in a broad array of clinical and translational investigations spanning the evaluation of basic pathophysiology in patients undergoing cardiac procedures, development and evaluation of new therapeutic strategies, and improving patient selection and outcomes following interventional procedures. We are comprised of a core group of faculty and dedicated research nurses as well as fellows, residents, and students. Projects range from investigator-initiated single-center observational studies to industry-sponsored multicenter phase 3 randomized controlled trials. We have established a database of all patients who have undergone TAVR at Johns Hopkins, which is providing the basis for several retrospective analyses and will serve as the foundation for future studies of TAVR. We are also engaged in collaborative projects with other groups from the Department of Medicine and other Departments including Cardiac Surgery, Anesthesiology, Radiology, Psychiatry, and Biomedical... Engineering. Members of our group are actively involved with the Johns Hopkins Center for Bioengineering Innovation and Design (CBID) in the development of novel minimally-invasive cardiovascular devices. view more