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Donald Shaffner Lab
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.
Elizabeth Wagner Lab
The Elizabeth Wagner Lab conducts research on several topics within the field of pulmonary medicine. Our key areas of investigation include angiogenesis of the lung and its dependence upon systemic vascularization to regions without pulmonary perfusion as well as the role of bronchial circulation in the uptake of hydrophilic particles that are delivered to the airway surface. In addition, we are conducting several specific studies that examine the relationship between the bronchial vasculature and the influx of inflammatory cells to a patientÕs airways.
Fredrick Wigley Lab
The Frederick Wigley Lab is interested in the signs, symptoms and causes of scleroderma. We are testing new treatments for RaynaudÕs phenomenon and scleroderma. Understanding the treatment approach to Raynaud's phenomenon and associated ischemia and how to prevent digital ulcers is important for clinicians caring for these patients. Work in our lab has provided guidance in the management of Raynaud's phenomenon and digital ischemic ulcers, including options for the practical pharmacologic and nonpharmacologic interventions.
Gregg Semenza Lab
The Gregg Semenza Lab studies the molecular mechanisms of oxygen homeostasis. We have cloned and characterized hypoxia-inducible factor 1 (HIF-1), a basic helix-loop-helix transcription factor.
Current research investigates the role of HIF-1 in the pathophysiology of cancer, cerebral and myocardial ischemia, and chronic lung disease, which are the most common causes of mortality in the U.S.
Research in the Jeffrey Dodd-o Lab aims to better understand the contributing factors of lung ischemia/reperfusion injuries and the role these injuries play in the lung dysfunction of patients soon after cardiopulmonary bypass surgery. We have created an ischemia/reperfusion model in a spontaneously breathing mouse that they use with an in situ mouse lung preparation to identify cardiopulmonary interactions that impact reperfusion-related lung injury. We are working to characterize the influence of atrial natriuretic peptide (ANP) on lung microvascular permeability.
Kayode Williams Lab
The Kayode Williams Lab conducts translational research on neuromodulation. We primarily examine the mechanisms and efficacy of spinal cord stimulation in treating neuropathic pain, peripheral neuropathies and peripheral vascular disease. Our clinical trials explore spinal cord stimulation in the treatment of painful diabetic neuropathy and the treatment of critical non-reconstructible critical leg ischemia. We also have a longstanding interest in the business of medicine and seek to enhance value propositions for hospitals and physician groups through more effective management of resources.
The MR Research Laboratory focuses on developing and applying nuclear magnetic resonance (NMR) techniques and on measuring energy metabolites and metabolic fluxes with phosphorous (31P) and proton (1H) MRS in patients with ischemia, infarction and heart failure.
Specific studies include: Phosphorus MR studies of myocardial energy metabolism in human heart: We have used spatially localized phosphorus MR spectroscopy (MRS) to noninvasively measure high-energy phosphate metabolites such as ATP (adenosine triphosphate) and phosphocreatine (PCr) in the heart. The PCr/ATP ratio can change during stress-induced ischemia, and a protocol for stress-testing in the MR system has been developed which can detect the changes noninvasively in the anterior wall. Additionally, we've developed methods for noninvasively measuring the creatine kinase (CK) ATP energy supply and used it to measure the CK ATP energy supply in the healthy heart at rest and exercise, in human myocardial infarction, and in ...human heart failure.
Interventional MRI technology: We are developing an RF dosimeter that measures incident-specific absorption rates applied during MRI independent of the scanner and developing MRI-safe internal detectors for higher field use. Outcomes of this research include the "MRI endoscope" that provides real-time, high-resolution views of vessel anatomy and a radiometric approach to detect any local heating associated with the device.
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