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.

Research in the Lisa Yanek Lab focuses on cardiovascular disease in families and risk factor modification. Recently, we conducted a study to determine the association of lean versus fat mass with fitness in healthy, overweight and obese African Americans from families with early-onset coronary disease.

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.

Work in the Lewis Romer Lab focuses on the responses of vascular systems to disease and injury. Using cultured human endothelial cells and fibroblasts from mice that lack expression of the FAK- or Src-family kinases, we’re exploring several topics. These include the effect of inflammatory cytokine on cell adhesion to the extracellular matrix; the role of FAK signaling in inhibiting apoptosis; and the function of FAK- and Src-family kinases in cell-matrix interactions during adhesion and motility.

Research in the Lee Bone Lab uses community-based participatory approaches to promote health in underserved urban African-American populations. We conduct randomized clinical trials on cardiovascular disease, diabetes and cancer detection and control in order to test the success of community interventions. We focus in particular on making interventions sustainable and on implementing electronic education to improve communication.

The Nauder Faraday Lab investigates topics within perioperative genetic and molecular medicine. We explore thrombotic, bleeding and infectious surgical complications. Our goal is to uncover the molecular determinants of outcome in surgical patients, which will enable surgeons to better personalize a patient’s care in the perioperative period. Our team is funded by the National Institutes of Health to research platelet phenotypes, the pharmacogenomics of antiplatelet agents for preventing cardiovascular disease, and the genotypic determinants of aspirin response in high-risk families.

The Nicholas Flavahan Lab primarily researches the cellular interactions and subcellular signaling pathways that control normal vascular function and regulate the initiation of vascular disease. We use biochemical and molecular analyses of cellular mediators and cell signaling mechanisms in cultured vascular cells, while also conducting physiological assessments and fluorescent microscopic imaging of signaling systems in isolated blood vessels. A major component of our research involves aterioles, tiny blood vessles that are responsible for controlling the peripheral resistance of the cardiovascular system, which help determine organ blood flow.

The Retinal Cell and Molecular Laboratory has three major areas of interest, each of which deals with some aspect of growth factor signaling and function in the retina and retinal pigmented epithelium (RPE): 1. Investigations aimed at gaining a better understanding of the pathogenesis of retinal and choroidal neovascularization and developing new ways to treat them. 2. Investigations aimed at understanding the molecular signals involved in retinal and RPE wound repair and scarring. The prototypical disease in this category is proliferative vitreoretinopathy and our laboratory is seeking to identify new treatments for it. 3. Investigations aimed at understanding why retinal degenerations occur and how they might be treated, with particular emphasis on neurotrophic factors.

Dr. Amir Kashani and his team are developing novel diagnostic and therapeutic methods to diagnose and treat retinal diseases using advanced imaging methods. These methods can detect the earliest changes in retinal capillaries before they are noticeable to the patient or doctor.

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.