Research in the Edgar Miller Lab focuses on nutrition, hypertension and kidney disease. Current projects include a National Heart, Lung, and Blood Institute study on dietary carbohydrate and glycemic index effects on markers of oxidative stress, inflammation and kidney function; and a National Institute of Diabetes and Digestive and Kidney Diseases randomized controlled trial that examines the effects of omega-3 fatty acid supplementation on urine protein excretion in diabetic kidney disease.

Dr. Paul A. Welling and his research team explore the genetic and molecular underpinnings of electrolyte physiology, potassium balance disorders, hypertension and kidney disease. A major thrust of current research activity is devoted to understanding how faulty genes and environmental stresses drive hypertension. The research is providing new insights into how the Western diet triggers deleterious responses of salt-sensitivity genes. The Welling laboratory employs a multidisciplinary approach, spanning from gene discovery, molecular biology, genetically engineered mouse models to translational studies in humans. By illuminating pathophysiological mechanisms and translating the discoveries to develop more effective diagnostic and therapeutic strategies, Welling’s group is striving to improve the health of at-risk individuals and patients with kidney disease and hypertension.

Dr. Welling is the Joseph S. and Esther Hander Professor of Laboratory Research in Nephrology. He has been continuously funded by the National Institutes of Health for over 25 years. Currently he serves as Coordinator of a Global Research Network, funded by the LeDucq Foundation. More about his research can be found at https://www.wellinglab.com/

Basic science investigations span an array of inquiries, such as understanding the basic mechanisms underlying cardiac dyssynchrony and resynchronization in the failing heart, and beneficial influences of nitric oxide/cGMP/protein kinase G and cGMP-targeted phosphdiesterase signaling cascades on cardiac maladaptive stress remodeling. Recently, the latter has particularly focused on the role of phosphodiesterase type 5 and its pharmacologic inhibitors (e.g. sildenafi, Viagra®), on myocyte signaling cascades modulated by protein kinase G, and on the nitric oxide synthase dysregulation coupled with oxidant stress. The lab also conducts clinical research and is presently exploring new treatments for heart failure with a preserved ejection fraction, studying ventricular-arterial interaction and its role in adverse heart-vessel coupling in left heart failure and pulmonary hypertension, and testing new drug, device, and cell therapies for heart disease. A major theme has been with the use of advanced non-invasive and invasive catheterization-based methods to assess cardiac mechanics in patients.asive and invasive catheterization-based methods to assess cardiac mechanics in patients. David Kass, MD, is currently the Director at the Johns Hopkins Center for Molecular Cardiobiology and a professor in cellular and molecular medicine.

In the Lee Martin Laboratory, we are testing the hypothesis that selective vulnerability--the phenomenon in which only certain groups of neurons degenerate in adult onset neurological disorders like amyotrophic lateral sclerosis and Alzheimer's disease--is dictated by brain regional connectivity, mitochondrial function and oxidative stress. We believe it is mediated by excitotoxic cell death resulting from abnormalities in excitatory glutamatergic signal transduction pathways, including glutamate transporters and glutamate receptors as well as their downstream intracellular signaling molecules. We are also investigating the contribution of neuronal/glial apoptosis and necrosis as cell death pathways in animal (including transgenic mice) models of acute and progressive neurodegeneration. We use a variety of anatomical and molecular neurobiological approaches, including neuronal tract-tracing techniques, immunocytochemistry, immunoblotting, antipeptide antibody production, transmission electron microscopy and DNA analysis to determine the precise regional and cellular vulnerabilities and the synaptic and molecular mechanisms that result in selective neuronal degeneration.

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.

The Older Americans Independence Center (OAIC) studies frailty, an age-related condition in which older adults lose the capacity to cope with stressors and become vulnerable to functional decline, loss of independence and mortality. Since its original funding in 2003, the center has helped demonstrate that frailty is a syndrome caused by multiple biological mechanisms that are expressed through characteristics of decreased resiliency and reserve in older adults. The mission of OAIC is to provide a hypothesis-driven, frailty-focused, highly interdisciplinary center where supported investigators receive the expertise, resources and training necessary to make fundamental discoveries related to the origins and causes of frailty and then move these discoveries towards frailty-focused interventions.

David Hackam’s laboratory focuses on necrotizing enterocolitis (NEC), a devastating disease of premature infants and the leading cause of death and disability from gastrointestinal disease in newborns. The disease strikes acutely and without warning, causing sudden death of the small and large intestines. In severe cases, tiny patients with the disease are either dying or dead from overwhelming sepsis within 24 hours. Surgical treatment to remove most of the affected gut results in lifelong short gut (short bowel) syndrome. The Hackam Lab has identified a critical role for the innate immune receptor toll-like receptor 4 (TLR4) in the pathogenesis of necrotizing enterocolitis. The lab has shown that TLR4 regulates the development of the disease by tipping the balance between injury and repair in the stressed intestine of the premature infant. Developing an Artificial Intestine A key goal is to create, in the laboratory, new intestines made from patients’ own cells, which can then be implanted into the patient to restore normal digestive function. This innovative design could transform child development and quality of life in necrotizing enterocolitis survivors without the risks of conventional donor transplant.

The Brain Health Program is a multidisciplinary team of faculty from the departments of neurology, psychiatry, epidemiology, and radiology lead by Leah Rubin and Jennifer Coughlin. In the hope of revealing new directions for therapies, the group studies molecular biomarkers identified from tissue and brain imaging that are associated with memory problems related to HIV infection, aging, dementia, mental illness and traumatic brain injury. The team seeks to advance policies and practices to optimize brain health in vulnerable populations while destigmatizing these brain disorders. Current and future projects include research on: the roles of the stress response, glucocorticoids, and inflammation in conditions that affect memory and the related factors that make people protected or or vulnerable to memory decline; new mobile apps that use iPads to improve our detection of memory deficits; clinical trials looking at short-term effects of low dose hydrocortisone and randomized to 28 days of treatment; imaging brain injury and repair in NFL players to guide players and the game; and the role of inflammation in memory deterioration in healthy aging, patients with HIV, and other neurodegenerative conditions.

The Robinson Lab studies the way in which mechanical stress guide and direct the behavior of cells, including when they are part of tissues, organs and organ systems.

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. Medical 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.