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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
Aravinda Chakravarti's Lab
Aravinda Chakravarti's Lab focuses on the development and applications of genetic, genomic, and computational technologies and perspectives for gene discovery in a variety of complex human diseases.
Our goal is to assess how genomic information can be used in modern clinical medicine in the era of personalized medicine. Specifically, we use a variety of disease models to infer the features of complex disease gene architecture in birth defects (namely, Hirschsprung disease), cardiovascular disorders (including hypertension and sudden cardiac death) and mental illness (autism, bipolar disease and schizophrenia).
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
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.
CORE-320 Multicenter Trial Lab
The central theme of the CORE-320 Multicenter Trial Lab’s research is to support the Coronary Artery Evaluation Using 320-Row Multidetector CT Angiography (CORE 320) study, a multi-center multinational diagnostic study with the primary objective to evaluate the diagnostic accuracy of 320-MDCT for detecting coronary artery luminal stenosis and corresponding myocardial perfusion deficits in patients with suspected CAD compared with the reference standard of conventional coronary angiography and SPECT myocardial perfusion imaging.
Armin Arbab-Zadeh, MD, PhD, is an associate professor of medicine at the Johns Hopkins University School of Medicine and Director of Cardiac Computed Tomography in the Division of Cardiology at the Johns Hopkins Hospital in Baltimore.
Research Areas: coronary/cardiac imaging, coronary risk prediction, heart attack prevention, cardiac computed tomography, coronary circulation and disease
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.
The main focus of Dr. Gilotra's research is understanding the pathophysiology and outcomes in inflammatory cardiomyopathies including myocarditis and sarcoidosis, as well as improvement of heart failure patient care through noninvasive hemodynamic monitoring and studying novel strategies to reduce heart failure hospitalizations. Additional investigations involve clinical research in advanced heart failure therapies including heart transplantation and mechanical circulatory support. Dr. Gilotra is the site Principal Investigator for the NIH/NHLBI funded Heart Failure Network trials.
Interventional Cardiology Research Group
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
Joseph Mankowski Lab
The Joseph Mankowski Lab studies the immunopathogenesis of HIV infection using the SIV/macaque model. Our researchers use a multidisciplinary approach to dissect the mechanism underlying HIV-induced nervous system and cardiac diseases. Additionally, we study the role that host genetics play in HIV-associated cognitive disorders.
Molecular and Comparative Pathobiology
Basic science investigations span an array of inquiries, such as understanding the basic mechanisms underlying cardiac dyssynchrony and resynchronization in the failing heart, and beneficial influences of nitric oxide/cGMP/protein kinase G and cGMP-targeted phosphdiesterase signaling cascades on cardiac maladaptive stress remodeling. Recently, the latter has particularly focused on the role of phosphodiesterase type 5 and its pharmacologic inhibitors (e.g. sildenafi, Viagra®), on myocyte signaling cascades modulated by protein kinase G, and on the nitric oxide synthase dysregulation coupled with oxidant stress.
The lab also conducts clinical research and is presently exploring new treatments for heart failure with a preserved ejection fraction, studying ventricular-arterial interaction and its role in adverse heart-vessel coupling in left heart failure and pulmonary hypertension, and testing new drug, device, and cell therapies for heart disease. A major theme has been with the use ...of advanced non-invasive and invasive catheterization-based methods to assess cardiac mechanics in patients.asive and invasive catheterization-based methods to assess cardiac mechanics in patients.
David Kass, MD, is currently the Director at the Johns Hopkins Center for Molecular Cardiobiology and a professor in cellular and molecular medicine. view more
The Lima Lab’s research is concentrated on the development and application of imaging and technology to address scientific and clinical problems involving the heart and vascular system.
Specifically, our research is focused on developing magnetic resonance imaging (MRI) contrast techniques to investigate microvascular function in patients and experimental animals with myocardial infarction; functional reserve secondary to dobutamine stimulation and myocardial viability assessed by sodium imaging; and cardiac MRI and computed tomography (CT) program development of techniques to characterize atherosclerosis in humans with cardiovascular or cerebrovascular disease.
Current projects include:
• The Coronary Artery Risk Development in Young Adults (CARDIA) Study
• The MESA (Multi-Ethnic Study of Atherosclerosis) Study
• The Coronary Artery Evaluation using 64-row Multidetector Computed Tomography Angiography (CORE64) Study
Joao Lima, MD, is a professor of medicine, radiology and... epidemiology at the Johns Hopkins School of Medicine. view more
Research in the Mary Beth Brady Lab focuses primarily on topics within the fields of anesthesiology, imaging and cardiology. Our work has explored transesophageal echocardiography simulation, echocardiography, cardiac and vascular-thoracic anesthesiology, and other areas within critical care medicine. A recent study involved obtaining 3-D images of the heart, which were then used to build computer programs to help cardiac surgeons improve their treatment of heart defects.
The O’Rourke Lab uses an integrated approach to study the biophysics and physiology of cardiac cells in normal and diseased states.
Research in our lab has incorporated mitochondrial energetics, Ca2+ dynamics, and electrophysiology to provide tools for studying how defective function of one component of the cell can lead to catastrophic effects on whole cell and whole organ function. By understanding the links between Ca2+, electrical excitability and energy production, we hope to understand the cellular basis of cardiac arrhythmias, ischemia-reperfusion injury, and sudden death.
We use state-of-the-art techniques, including single-channel and whole-cell patch clamp, microfluorimetry, conventional and two-photon fluorescence imaging, and molecular biology to study the structure and function of single proteins to the intact muscle. Experimental results are compared with simulations of computational models in order to understand the findings in the context of the system as a whole....
Ongoing studies in our lab are focused on identifying the specific molecular targets modified by oxidative or ischemic stress and how they affect mitochondrial and whole heart function.
The motivation for all of the work is to understand
• how the molecular details of the heart cell work together to maintain function and
• how the synchronization of the parts can go wrong
Rational strategies can then be devised to correct dysfunction during the progression of disease through a comprehensive understanding of basic mechanisms.
Brian O’Rourke, PhD, is a professor in the Division of Cardiology and Vice Chair of Basic and Translational Research, Department of Medicine, at the Johns Hopkins University. view more
The Post Lab is involved in the Multi-Ethnic Study of Atherosclerosis (MESA), a collaborative study of the characteristics of subclinical cardiovascular disease (that is, disease detected non-invasively before it has produced clinical signs and symptoms) and the risk factors that predict progression to clinically overt cardiovascular disease or progression of the subclinical disease.
As MESA researchers, we study a diverse, population-based sample of 6,814 asymptomatic men and women aged 45-84. Approximately 38 percent of the recruited participants are white, 28 percent African-American, 22 percent Hispanic, and 12 percent Asian, predominantly of Chinese descent.
Participants were recruited from six field centers across the United States, including Johns Hopkins University. Each participant received an extensive physical exam to determine a number of conditions, including coronary calcification, ventricular mass and function, flow-mediated endothelial vasodilation, standard coron...ary risk factors, sociodemographic factors, lifestyle factors, and psychosocial factors.
Selected repetition of subclinical disease measures and risk factors at follow-up visits have allowed study of the progression of disease. Participants are being followed for identification and characterization of cardiovascular disease events, including acute myocardial infarction and other forms of coronary heart disease (CHD), stroke, and congestive heart failure; for cardiovascular disease interventions; and for mortality.
Wendy S. Post, MD, MS, is an associate faculty, Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, and a professor of medicine. view more
Research in the Retrovirus Laboratory focuses on the molecular virology and pathogenesis of lentivirus infections. In particular, we study the simian immunodeficiency virus (SIV) to determine the molecular basis for the development of HIV CNS, pulmonary and cardiac disease.
Research projects include studies of viral molecular genetics and host cell genes and proteins involved in the pathogenesis of disease. We are also interested in studies of lentivirus replication in macrophages and astrocytes and their role in the development of disease. These studies have led us to identify the viral genes that are important in neurovirulence of SIV and the development of CNS disease including NEF and the TM portion of ENV. The mechanisms of the action of these proteins in the CNS are complex and are under investigation. We have also developed a rapid, consistent SIV/macaque model in which we can test the ability of various antiviral and neuroprotective agents to reduce the severity of CNS and ...pulmonary disease. view more
Molecular and Comparative Pathobiology
The Arking Lab
The Arking Lab studies the genomics of complex human disease, with the primary goal of identifying and characterizing genetics variants that modify risk for human disease. The group has pioneered the use of genome-wide association studies (GWAS), which allow for an unbiased screen of virtually all common genetic variants in the genome. The lab is currently developing improved GWAS methodology, as well as exploring the integration of additional genome level data (RNA expression, DNA methylation, protein expression) to improve the power to identify specific genetic influences of disease.
The Arking Lab is actively involved in researching:
• autism, a childhood neuropsychiatric disorder
• cardiovascular genomics, with a focus on electrophysiology and sudden cardiac death (SCD)
• electrophysiology is the study of the flow of ions in biological tissues
Dan E. Arking, PhD, is an associate professor at the McKusick-Nathans Institute of Genetic Medicine and Department of Medicine, D...ivision of Cardiology, Johns Hopkins University. view more
The Atlantic Cardiovascular Patient Outcomes Research Team - Atlantic C-PORT
Our research is centered on the safety, efficacy and outcomes of PCI performed at hospitals without on-site cardiac surgery.
C-PORT Randomized Studies and Registries; New Jersey Angioplasty Demonstration Project; InCar-decision support tools for performance of PCI at hospitals without on-site cardiac surgery.
For more information please visit Cport.org.
The Barouch Lab
The Barouch Lab is focused on defining the peripheral cardiovascular effects of the adipocytokine leptin, which is a key to the understanding of obesity-related cardiovascular disease. Interestingly, many of the hormonal abnormalities seen in obesity are mimicked in heart failure. The research program will enhance the understanding of metabolic signaling in the heart, including the effects of leptin, exercise, sex hormones, and downstream signaling pathways on metabolism and cardiovascular function.
The lab also is working to determine the precise role of the “metabolic” beta-3 adrenergic receptor (ß3AR) in the heart and define the extent of its protective effect in obesity and in heart failure, including its role in maintaining nitric oxide synthase (NOS) coupling. Ultimately, this work will enable the exploration of a possible therapeutic role of ß3AR agonists and re-coupling of NOS in preventing adverse ventricular remodeling in obesity and in heart failure.
Lili Barouch, MD,... is an associate professor of medicine in the Division of Cardiology and a member of the Advanced Heart Failure and Cardiac Transplantation group at the Johns Hopkins University School of Medicine. view more
The Weiss Lab, which features a multi-disciplinary team at Johns Hopkins as well as at Cedars Sinai Medical Center in Los Angeles, is dedicated to identifying the most important clinical, genetic, structural, contractile and metabolic causes of sudden cardiac death as well as the means to reverse the underlying pathology and lower risk.
Current projects include research into energy metabolism in human heart failure and creatine kinase metabolism in animal models of heart failure.
Robert G. Weiss, MD, is professor of medicine, Radiology and Radiological Science, at the Johns Hopkins University.