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
Investigators in the Lakshmi Santhanam Lab examine the fundamental mechanisms behind cardiovascular disease. They are particularly interested in better understanding how nitric oxide-mediated S-nitrosylation (a post-translational protein modification) impacts protein function and trafficking in the vasculature as well as how this relationship influences matrix remodeling and vascular stiffening.
Our laboratory conducts basic and translational research aimed at better understanding the pathogenesis of multiple sclerosis (MS) and the role of the immune system in CNS disease, particularly the processes that drive progressive disability such as neurodegeneration and remyelination failure. We currently have three parallel research programs: 1. Metabolism as a modulator of MS: We are studying how basic metabolic pathways regulate the immune system and how these pathways might be exploited to protect neurons and myelin-forming oligodendrocytes from injury. 2. Identifying pathways by which nitric oxide (NO) and other free radicals cause neuronal and axonal damage. Our lab is identifying specific signaling pathways initiated by NO and other free radicals that can be targeted by drugs to produce neuroprotection. 3. Modulating the innate immune system in MS: In collaboration with others at Johns Hopkins, we are studying ways to enhance the reparative functions of microglia while preventi...ng maladaptive responses. This work has identified bryostatin-1 as a potential drug that may be re-purposed for this task.view more
Information processing in the brain reflects communication among neurons via neurotransmitters. The Solomon Snyder Laboratory studies diverse signaling systems including those of neurotransmitters and second messengers as well as the actions of drugs upon these processes. We are interested in atypical neurotransmitters such as nitric oxide (NO), carbon monoxide (CO), and the D-isomers of certain amino acids, specifically D-serine and D-aspartate. Our discoveries are leading to a better understanding of how certain drugs for Parkinson's disease and Hungtington's disease interact with cells and proteins. Understanding how other second messengers work is giving us insight into anti-cancer therapies.
The Ted Dawson Laboratory uses genetic, cell biological and biochemical approaches to explore the pathogenesis of Parkinson's disease (PD) and other neurologic disorders. We also investigate several discrete mechanisms involved in cell death, including the role of nitric oxide as an endogenous messenger, the function of poly (ADP-ribose) polymerase-1 and apoptosis inducing factor in cell death, and how endogenous cell survival mechanisms protect neurons from death.
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