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 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.

Dr. Rabb’s lab is involved in translational research aimed at understanding the molecular pathogenesis of kidney ischemia/reperfusion injury. The lab is interested in the development of novel treatments for kidney IRI.

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.

Research in the Jonathan Orens Lab examines topics such as clinical outcomes of lung transplantation, chronic allograft rejection and ischemic reperfusion injury, also known as primary graft dysfunction.

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 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.

Our research interest is crystalized into three main areas: 1. Type-1 diabetes - Our focus is on understanding how the Fas death pathway regulates the disease and how extracted information can be used to protect high risk individuals and those with new-onset disease. 2. Type 2 diabetes and Obesity - Our lab is studying the role of heparan sulfate proteoglycans (HSPG) in regulating body fat and glucose clearance. 3. Double negative ??T cells - Our studies suggest a critical role for these cells in protecting kidneys from Ischemia reperfusion injury (IRI). Our current focus is understanding their origin and physiological functions.

Research in the Raymond Koehler Lab explores cerebrovascular physiology and cerebral ischemic injury caused by stroke and cardiac arrest, using protein analysis, immunohistochemistry and histology. We also study ischemic preconditioning, neonatal hypoxic-ischemic encephalopathy and the mechanisms of abnormal cerebrovascular reactivity after ischemia. We 're examining ways to improve tissue oxygenation and seek to better understand the mechanisms that connect an increase in cerebral blood flow to neuronal activity.