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Research in the Anderson laboratory focuses on cellular signaling and ionic mechanisms that cause heart failure, arrhythmias and sudden cardiac death, major public health problems worldwide. Primary focus is on the multifunctional Ca2+ and calmodulin-dependent protein kinase II (CaMKII). The laboratory identified CaMKII as an important pro-arrhythmic and pro-cardiomyopathic signal, and its studies have provided proof of concept evidence motivating active efforts in biotech and the pharmaceutical industry to develop therapeutic CaMKII inhibitory drugs to treat heart failure and arrhythmias.
Under physiological conditions, CaMKII is important for excitation-contraction coupling and fight or flight increases in heart rate. However, myocardial CaMKII is excessively activated during disease conditions where it contributes to loss of intracellular Ca2+ homeostasis, membrane hyperexcitability, premature cell death, and hypertrophic and inflammatory transcription. These downstream targets a...ppear to contribute coordinately and decisively to heart failure and arrhythmias. Recently, researchers developed evidence that CaMKII also participates in asthma.
Efforts at the laboratory, funded by grants from the National Institutes of Health, are highly collaborative and involve undergraduate assistants, graduate students, postdoctoral fellows and faculty. Key areas of focus are:
• Ion channel biology and arrhythmias
• Cardiac pacemaker physiology and disease
• Molecular physiology of CaMKII
• Myocardial and mitochondrial metabolism
• CaMKII and reactive oxygen species in asthma
Mark Anderson, MD, is the William Osler Professor of Medicine, the director of the Department of Medicine in the Johns Hopkins University School of Medicine and physician-in-chief of The Johns Hopkins Hospital. view less
Mitochondrial dysfunction has long been a consistent observation in Parkinson's disease. To understand the consequences of Parkinson's disease causing genetic mutations on the function of mitochondria, the Bioenergetics Core B will provide the following analyses to the projects in the Udall Center at Johns Hopkins: (1) Measuring rates of respiration, oxygen consumption and ATP generation, (2) Measuring calcium dynamics, (3) Measuring reactive oxygen and reactive nitrogen species, (4) Measuring the activity of the electron transport chain enzymes and metabolic enzymes, and (5) Measuring plasma versus mitochondrial membrane potential and mitochondrial membrane permeability
The Espenshade Lab uses a multi-organismal and multidisciplinary approach to understand how eukaryotic cells measure insoluble lipids and dissolved gases. We have chosen cholesterol and oxygen as our model molecules, based on their essential roles in cell function and the importance of their proper homeostasis for human health.
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 John Ulatowski Lab explores the regulatory mechanisms of oxygen delivery to the brain and cerebral blood flow. Our work includes developing and applying new techniques and therapies for stroke as well as non-invasive techniques for monitoring brain function, fluid management and sedation in brain injury patients. We also examine the use of novel oxygen carriers in blood. We’ve recently begun exploring new methods for perioperative and periprocedural care that would help to optimize patient safety in the future.
Dr. Hua's research has centered on the development of novel MRI technologies for in vivo functional and physiological imaging in the brain, and the application of such methods for studies in healthy and diseased brains. These include the development of human and animal MRI methods to measure functional brain activities, cerebral perfusion and oxygen metabolism at high (3 Tesla) and ultra-high (7 Tesla and above) magnetic fields. He is particularly interested in novel MRI approaches to image small blood and lymphatic vessels in the brain. Collaborating with clinical investigators, these techniques have been applied 1) to detect functional, vascular and metabolic abnormalities in the brain in neurodegenerative diseases such as Huntingdon's disease (HD), Parkinson's disease (PD), Alzheimer's disease (AD) and mental disorders such as schizophrenia; and 2) to map brain functions and cerebrovascular reactivity for presurgical planning in patients with vascular malformations, brain tumors and... epilepsy. view more
Dr. Fridman's research group invents and develops bioelectronics for Neuroengineering and Medical Instrumentation applications. We develop innovative medical technology and we also conduct the necessary biological studies to understand how the technology could be effective and safe for people.
Our lab is currently focused on developing the "Safe Direct Current Stimulation" technology, or SDCS. Unlike the currently available commercial neural prosthetic devices, such as cochlear implants, pacemakers, or Parkinson's deep brain stimulators that can only excite neurons, SDCS can excite, inhibit, and even sensitize them to input. This new technology opens a door to a wide range of applications that we are currently exploring along with device development: e.g. peripheral nerve stimulation for suppressing neuropathic pain, vestibular nerve stimulation to correct balance disorders, vagal nerve stimulation to suppress an asthma attack, and a host of other neuroprosthetic applications.
M...edical Instrumentation MouthLab is a "tricorder" device that we invented here in the Machine Biointerface Lab. The device currently obtains all vital signs within 60s: Pulse rate, breathing rate, temperature, blood pressure, blood oxygen saturation, electrocardiogram, and FEV1 (lung function) measurement. Because the device is in the mouth, it has access to saliva and to breath and we are focused now on expanding its capability to obtaining measures of dehydration and biomarkers that could be indicative of a wide range of internal disorders ranging from stress to kidney failure and even lung cancer.
Mark Liu Lab
Research in the Mark Liu Lab explores several areas of pulmonary and respiratory medicine. Our studies primarily deal with allergic inflammation, chronic obstructive pulmonary disease (COPD) and asthma, specifically immunologic responses to asthma. We have worked to develop a microfluidic device with integrated ratiometric oxygen sensors to enable long-term control and monitoring of both chronic and cyclical hypoxia. In addition, we conduct research on topics such as the use of magnetic resonance angiography in evaluating intracranial vascular lesions and tumors as well as treatment of osteoporosis by deep sea water through bone regeneration.
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.
Roy Brower Lab
The Roy Brower Lab conducts clinical trials related to the management of acute respiratory distress syndrome (ARDS). Our research also involves oxygen toxicity, a potentially fatal condition caused by too much supplemental oxygen.