Over the last few decades, a growing body of evidence has shown that the immune system is intimately connected with cardiac development, function and adaptation to injury. However, there is still much to learn and currently there are no immunomodulatory treatments to prevent or treat heart dysfunction. The Adamo Lab aims to study applied immunology in the context of cardiac function and dysfunction, to both elucidate fundamental properties of the immune systems and to develop novel therapeutic options for the rapidly growing number of patients living with heart disease.

Our group is interested in 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.

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 learn 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.

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. Active Projects: • Quantification of desmin PTM-forms in different forms of heart failure at the peptide level using mass spectrometry • Functional 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

Our research is centered on the safety, efficacy and outcomes of PCI performed at hospitals without on-site cardiac surgery. Active projects: 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.

Work in the Donald Shaffner Lab investigates several topics within critical care medicine. Our team conducts research on the mechanisms involved in neurologic injury from global ischemia as a result of cardiac arrest and resuscitation. We also study neurologic outcomes of pediatric patients who experience cardiac arrest.

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.

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.

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.

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.