The Systems Biology Lab applies methods of multiscale modeling to problems of cancer and cardiovascular disease, and examines the systems biology of angiogenesis, breast cancer and peripheral artery disease (PAD). Using coordinated computational and experimental approaches, the lab studies the mechanisms of breast cancer tumor growth and metastasis to find ways to inhibit those processes. We use bioinformatics to discover novel agents that affect angiogenesis and perform in vitro and in vivo experiments to test these predictions. In addition we study protein networks that determine processes of angiogenesis, arteriogenesis and inflammation in PAD. The lab also investigates drug repurposing for potential applications as stimulators of therapeutic angiogenesis, examines signal transduction pathways and builds 3D models of angiogenesis. The lab has discovered over a hundred novel anti-angiogenic peptides, and has undertaken in vitro and in vivo studies testing their activity under different conditions. We have investigated structure-activity relationship (SAR) doing point mutations and amino acid substitutions and constructed biomimetic peptides derived from their endogenous progenitors. They have demonstrated the efficacy of selected peptides in mouse models of breast, lung and brain cancers, and in age-related macular degeneration.

Researchers in the Adrian Dobs Lab study topics that include gonadal dysfunction, hyperlipidemia, diabetes mellitus, and the relationship between sex hormones and heart disease. We currently are investigating male gonadal function—with particular interest in new forms of male hormone replacement therapy—and hormonal changes related to aging.

Researchers in the Ami Shah Lab study scleroderma and Raynaud’s phenomenon. We examine the relationship between cancer and scleroderma, with a focus on how and if cancer causes scleroderma to develop in some patients. We are currently conducting clinical research to study ways to detect cardiopulmonary complications in patients with scleroderma, biological and imaging markers of Raynaud’s phenomenon, and drugs that improve aspects of scleroderma.

Work in the Wei Dong Gao Lab primarily focuses on heart failure and defining molecular and cellular mechanisms of contractile dysfunction. We use molecular biology and proteomic techniques to investigate the changes that myofilament proteins undergo during heart failure and under drug therapy. We're working to determine the molecular nature of nitroxyl (HNO) modification of tropomyosin.

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.

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.

Research in the Rita Kalyani Lab examines the decreased physical functioning observed in patients with diabetes as they age. Through several ongoing epidemiological cohorts, we are investigating the association of high blood glucose and high insulin levels with accelerated muscle loss, and possible contributions to the physical disability observed in diabetes. We are currently involved in clinical studies that aim to understand the underlying mechanisms for these associations and to facilitate the development of novel strategies to prevent muscle loss and disability in people with diabetes.

The lab’s assets include three MRI systems available for pediatric studies, cardiac imaging processing, cardiovascular imaging and therapeutic ultrasound. A robust echocardiogram program conducts 10,000 transthoracic echocardiograms and 1,300 fetal echocardiograms per year, and maintains a database with 10 years of data.

Dr. Williams' research focuses on platelet physiology particularly as it relates to acute coronary syndromes and depression. Her laboratory specifically examines platelet aggregation, flow cytometric analysis to measure platelet activation, platelet luminescence as a measure of the platelet release reaction, many Elisa preparations in order to measure platelet function, platelet genotyping to determine the presence of certain platelet polymorphisms, and various other assays to distinguish mechanisms of platelet dysfunction. The goal for her cardiovascular platelet laboratory is to identify the etiology of platelet dysfunction in many disease states and apply methods that may improve this dysfunction that can eventually be translated to therapies for patients with cardiovascular disease. Scientific techniques performed in the lab include: flow cytometric analysis, platelet microparticle identification, and protein immunoprecipitation among other techniques.

The Allan Gelber Lab conducts research on the clinical epidemiology of rheumatic disorders. Our recent studies have explored topics that include the predicting factors of prevalent and incident gout; cardiovascular disease burden and risk in patients with rheumatoid arthritis; autoantibodies in both primary and secondary SjogrenÕs syndrome; and predictors of outcomes in patients with scleroderma. In addition, we have a long-standing interest in the ways in which racial differences affect disease manifestations in relation to rheumatic disorders.