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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
Andrew Lane Lab
The Lane laboratory is focused on understanding molecular mechanisms underlying chronic rhinosinusitis, particularly the pathogenesis of nasal polyps, as well as inflammation on the olfactory epithelium. Diverse techniques in molecular biology, immunology, and physiology are utilized to study epithelial cell innate immunity, olfactory loss, and response to viral infection. Ongoing work explores how epithelial cells of the sinuses and olfactory mucosa participate in the immune response and contribute to chronic inflammation. The lab creates and employs transgenic mouse models of chronic nasal/sinus inflammation to support research in this area. Collaborations are in place with the School of Public Health to explore mechanisms of anti-viral immunity in influenza and COVID-19.
The Cammarato Lab is located in the Division of Cardiology in the Department of Medicine at the Johns Hopkins University School of Medicine. We are interested in basic mechanisms of striated muscle biology.
We employ an array of imaging techniques to study “structural physiology” of cardiac and skeletal muscle. Drosophila melanogaster, the fruit fly, expresses both forms of striated muscle and benefits greatly from powerful genetic tools. We investigate conserved myopathic (muscle disease) processes and perform hierarchical and integrative analysis of muscle function from the level of single molecules and macromolecular complexes through the level of the tissue itself.
Anthony Ross Cammarato, MD, is an assistant professor of medicine in the Cardiology Department. He studies the identification and manipulation of age- and mutation-dependent modifiers of cardiac function, hierarchical modeling and imaging of contractile machinery, integrative analysis of striated muscle performan...ce and myopathic processes. view more
The Bergles Laboratory studies synaptic physiology, with an emphasis on glutamate transporters and glial involvement in neuronal signaling. We are interested in understanding the mechanisms by which neurons and glial cells interact to support normal communication in the nervous system. The lab studies glutamate transport physiology and function. Because glutamate transporters play a critical role in glutamate homeostasis, understanding the transporters' function is relevant to numerous neurological ailments, including stroke, epilepsy, and neurodegenerative diseases like amyotrophic lateral sclerosis (ALS). Other research in the laboratory focuses on signaling between neurons and glial cells at synapses. Understanding how neurons and cells communicate, may lead to new approaches for stimulating re-myelination following injury or disease. Additional research in the lab examines how a unique form of glia-to-neuron signaling in the cochlea influences auditory system development, whethe...r defects in cell communication lead to certain hereditary forms of hearing impairment, and if similar mechanisms are related to sound-induced tinnitus. view more
The Fu Lab is a basic research lab that studies zinc transport, with a particular focus on which step in the zinc transport process may be modulated and how. Dr. Fu's lab uses parallel cell biology and proteomic approaches to understand how these physiochemical principles are applied to mammalian zinc transporters and integrated to the physiology of pancreatic beta cells. This research has implications for understanding how zinc transport is related to diabetes and insulin intake.
Research in the Holland Lab focuses on the molecular mechanisms that control accurate chromosome distribution and the role that mitotic errors play in human health and disease. We use a combination of chemical biology, biochemistry, cell biology and genetically engineered mice to study pathways involved in mitosis and their effect on cell and organism physiology. One of our major goals is to develop cell and animal-based models to study the role of cell-division defects in genome instability and tumorigenesis.
The Human Brain Physiology and Stimulation Laboratory studies the mechanisms of motor learning and develops interventions to modulate motor function in humans. The goal is to understand how the central nervous system controls and learns to perform motor actions in healthy individuals and in patients with neurological diseases such as stroke. Using this knowledge, we aim to develop strategies to enhance motor function in neurological patients.
To accomplish these interests, we use different forms of non-invasive brain stimulation techniques, such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), as well as functional MRI and behavioral tasks.
J. Hunter Young Lab
Research in the J. Hunter Young Lab focuses on the genetic epidemiology and physiology of cardiovascular disease and its risk factors, especially hypertension, diabetes and obesity. Current activities include an observational study of hypertension among African Americans; a genetic epidemiology study of worldwide cardiovascular disease susceptibility patterns; and several population-based observational studies of cardiovascular and renal disease. A recent focus group study found that changes in housing and city policies might lead to improved environmental health conditions for public housing residents.
How do we see, hear, and think? More specifically, how can we study living people to understand how the brain sees, hears, and thinks? Recently, magnetic resonance imaging (MRI), a powerful anatomical imaging technique widely used for clinical diagnosis, was further developed into a tool for probing brain function. By sensitizing magnetic resonance images to the changes in blood oxygenation that occur when regions of the brain are highly active, we can make "movies" that reveal the brain at work. Dr. Pekar works on the development and application of this MRI technology.
Dr. Pekar is a biophysicist who uses a variety of magnetic resonance techniques to study brain physiology and function. Dr. Pekar serves as Manager of the F.M. Kirby Research Center for Functional Brain Imaging, a research resource where imaging scientists and neuroscientists collaborate to study brain function using unique state-of-the-art techniques in a safe comfortable environment, to further develop such techni...ques, and to provide training and education. Dr. Pekar works with center staff to serve the center's users and to keep the center on the leading edge of technology.
Joel Pomerantz Laboratory
The Pomerantz Laboratory studies the molecular machinery used by cells to interpret extracellular signals and transduce them to the nucleus to affect changes in gene expression. The accurate response to extracellular signals results in a cell's decision to proliferate, differentiate or die, and it's critical for normal development and physiology. The dysregulation of this machinery underlies the unwarranted expansion or destruction of cell numbers that occurs in human diseases like cancer, autoimmunity, hyperinflammatory states and neurodegenerative disease.
Current studies in the lab focus on signaling pathways that are important in innate immunity, adaptive immunity and cancer, with particular focus on pathways that regulate the activity of the pleiotropic transcription factor NF-kB.
Our research focuses on the biology of the peptidoglycan of Mycobacterium tuberculosis, the organism that causes tuberculosis, and Mycobacteroides abscessus, a related bacterium that causes opportunistic infections. We study basic mechanisms associated with peptidoglycan physiology but with an intent to leverage our findings to develop tools that will be useful in the clinic to treat mycobacterial infections.
Peptidoglycan is the exoskeleton of bacteria that not only provides structural rigidity and cell shape but also several vital physiological functions. Breaching this structure is often lethal to bacteria. We are exploring fundamental mechanisms by which bacteria synthesize and preserve their peptidoglycan. Although our lab uses genetic, biochemical and biophysical approaches to study the peptidoglycan, we pursue questions irrespective of the expertise required to answer those questions. It is through these studies that we identified synergy between two beta-lactam antibiotics a...gainst select mycobacteria. view more
Research in the Mark Donowitz Lab is primarily focused on the development of drug therapy for diarrheal disorders, intestinal salt absorption and the proteins involved including their regulation, and the use of human enteroids to understand intestinal physiology and pathophysiology. We study two gene families initially recognized by this laboratory: mammalian Na/H exchangers and the subgroup of PDZ domain containing proteins present in the brush border of epithelial cells called NHERF family. A major finding is that NHE3 exists simultaneously in different sized complexes in the brush border, which change separately as part of signal transduction initiated by mimics of the digestive process. Relevance to the human intestine is being pursued using mini-human intestine made from Lgr5+ stems cells made from intestinal biopsies and measuring function via two-photon microscopy.
Michael Wolfgang Laboratory
The Wolfgang Laboratory is interested in understanding the metabolic properties of neurons and glia at a mechanistic level in situ. Some of the most interesting, enigmatic and understudied cells in metabolic biochemistry are those of the nervous system. Defects in these pathways can lead to devastating neurological disease. Conversely, altering the metabolic properties of the nervous system can have surprisingly beneficial effects on the progression of some diseases. However, the mechanisms of these interactions are largely unknown.
We use biochemical and molecular genetic techniques to study the molecular mechanisms that the nervous system uses to sense and respond to metabolic cues. We seek to understand the neurometabolic regulation of behavior and physiology in obesity, diabetes and neurological disease.
Current areas of study include deconstructing neurometabolic pathways to understand the biochemistry of the nervous system and how these metabolic pathways impact animal beh...avior and physiology, metabolic heterogeneity and the evolution of metabolic adaptation. view less
The Spinal Research Laboratory is the world’s leading research lab dedicated to animal models of spinal conditions. Our goal is to improve care and surgical outcomes for patients with spinal problems. Using novel models and techniques, our investigators have created new ways to study tumors of the spinal cord and spinal column, spinal paralysis and spinal fusion physiology. In addition, they consistently test spinal devices for effectiveness.
Neuro-Vestibular and Ocular Motor Laboratory
In our laboratory we study the brain mechanisms of eye movements and spatial orientation.
-How magnetic stimulation through transcranial devices affects cortical brain regions
-Neural mechanisms underlying balance, spatial orientation and eye movement
-Mathematical models that describe the function of ocular motor systems and perception of spatial orientation
-Short- and long-term adaptive processes underlying compensation for disease and functional recovery in patients with ocular motor, vestibular and perceptual dysfunction
Developing and testing novel diagnostic tools, treatments, and rehabilitative strategies for patients with ocular motor, vestibular and spatial dysfunction
Nicholas Dalesio Lab
Research in the Nicholas Dalesio Lab is currently examining pre-surgical predictors of post-surgical respiratory complications in children with obstructive sleep apnea and sleep-disordered breathing; the impact of anesthesia and pharmacological agents on upper airway physiology; and techniques for pediatric airway imaging.
Our research is directed toward how the brain controls the movements of the eyes (including eye movements induced by head motion) using studies in normal human beings, patients and experimental animals. The focus is on mechanisms underlying adaptive ocular motor control. More specifically, what are mechanisms by which the brain learns to cope with the changes associated with normal development and aging as well as the damage associated with disease and trauma? How does the brain keep its eye movement reflexes properly calibrated? Our research strategy is to make accurate, quantitative measures of eye movements in response to precisely controlled stimuli and then use the analytical techniques of the control systems engineer to interpret the findings.
Research areas: 1) learning and compensation for vestibular disturbances that occur either within the labyrinth or more centrally within the brain, 2) the mechanisms by which the brain maintains correct alignment of the eyes to prevent d...iplopia and strabismus, and 3) the role of ocular proprioception in localizing objects in space for accurate eye-hand coordination.
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
The Peter van Zijl Laboratory focuses on developing new methodologies for using MRI and magnetic resonance spectroscopy (MRS) to study brain function and physiology. In addition, we are working to understand the basic mechanisms of the MRI signal changes measured during functional MRI (fMRI) tests of the brain. We are also mapping the wiring of the brain (axonal connections between the brains functional regions) and designing new technologies for MRI to follow where cells are migrating and when genes are expressed. A more recent interest is the development of bioorganic biodegradable MRI contrast agents. Our ultimate goal is to transform these technologies into fast methods that are compatible with the time available for multi-modal clinical diagnosis using MRI.