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The Lau Lab uses a combination of computational and experimental approaches to study the atomic and molecular details governing the function of protein complexes involved in intercellular communication. We study ionotropic glutamate receptors (iGluRs), which are ligand-gated ion channels that mediate the majority of excitatory synaptic transmission in the central nervous system. iGluRs are important in synaptic plasticity, which underlies learning and memory. Receptor dysfunction has been implicated in a number of neurological disorders.
Research in the Alex Kolodkin Laboratory is focused on understanding how neuronal connectivity is established during development. Our work investigates the function of extrinsic guidance cues and their receptors on axonal guidance, dendritic morphology and synapse formation and function. We have investigated how neural circuits are formed and maintained through the action of guidance cues that include semaphorin proteins, their classical plexin and neuropilin receptors, and also novel receptors. We employ a cross-phylogenetic approach, using both invertebrate and vertebrate model systems, to understand how guidance cues regulate neuronal pathfinding, morphology and synaptogenesis. We also seek to understand how these signals are transduced to cytosolic effectors. Though broad in scope, our interrogation of the roles played by semaphorin guidance cues provides insight into the regulation of neural circuit assembly and function. Our current work includes a relatively new interest in ...understanding the origins of laminar organization in the central nervous system. view less
Research in the Allan Gottschalk Lab focuses on the mechanisms behind neuropathic pain, chronic pain related to nerve injury. We are investigating biophysical models of the impact of general anesthesia on the central nervous system; informational aspects of sensory perception and the representation of sensory input; nonlinear dynamics of respiratory pattern generation; and acute perioperative pain.
Principal Investigator
Department
Researchers in the Center for Cell Dynamics study spatially and temporally regulated molecular events in living cells, tissues and organisms. The team develops and applies innovative biosensors and imaging techniques to monitor dozens of critical signaling pathways in real time. The new tools help them investigate the fundamental cellular behaviors that underlie embryonic development, wound healing, cancer progression, and functions of the immune and nervous systems.
The McCallion Laboratory studies the roles played by cis-regulatory elements (REs) in controlling the timing, location and levels of gene activation (transcription). Their immediate goal is to identify transcription factor binding sites (TFBS) combinations that can predict REs with cell-specific biological control--a first step in developing true regulatory lexicons.
As a functional genetic laboratory, we develop and implement assays to rapidly determine the biological relevance of sequence elements within the human genome and the pathological relevance of variation therein. In recent years, we have developed a highly efficient reporter transgene system in zebrafish that can accurately evaluate the regulatory control of mammalian sequences, enabling characterization of reporter expression during development at a fraction of the cost of similar analyses in mice. We employ a range of strategies in model systems (zebrafish and mice), as well as analyses in the human population, to illu...minate the genetic basis of disease processes. Our long-term objective is to use these approaches in contributing to improved diagnostic, prognostic and therapeutic strategies in patient care. view more
Research in the Bradley Undem Lab centers around the hypothesis that the peripheral nervous system is directly involved in the processes of inflammation. This hypothesis is being studied primarily in the central airways and sympathetic ganglia. We are addressing this in a multidisciplinary fashion, using pharmacological, electrophysiological, biochemical and anatomical methodologies.
The Brain Science Institute (BSi) brings together both basic and clinical neuroscientists from across the Johns Hopkins campuses. The BSi represents one of the largest and most diverse groups in the university. The BSi's mission is to solve fundamental questions about brain development and function and to use these insights to understand the mechanisms of brain disease. This new knowledge will provide the catalyst for the facilitation and development of effective therapies. The goals of our research are to foster new programs in basic neuroscience discovery; initiate a translational research program that will develop new treatments for brain-based diseases; and encourage collaboration, interdisciplinary teams, and new thinking that will have a global influence on research and treatment of the nervous system.
The Center for Nanomedicine engineers drug and gene delivery technologies that have significant implications for the prevention, treatment and cure of many major diseases facing the world today. Specifically, we are focusing on the eye, central nervous system, respiratory system, women's health, gastrointestinal system, cancer, and inflammation.
We are a unique translational nanotechnology effort located that brings together engineers, scientists and clinicians working under one roof on translation of novel drug and gene delivery technologies
In the computational neuroscience Laboratory, we construct quantitative models of biological nervous systems that are firmly based on their neurophysiology, neuroanatomy and behavior, and that are developed in close interaction with experimentalists. Our main interest is neuronal function at the system level, reflecting the interaction of subsystems to generate useful behavior. Modeling is particularly important for understanding this and other system-level functions, since it requires the interaction of several pathways and neural functions.
One of the functions we study is selective attention--that is, the capability of higher animals to scan sensory input for the most important information and to discard all other. Models of the neuronal basis of visual selective attention are constructed by simulating them on digital computers and comparing the results with data obtained from the visual and somatosensory systems of primates. We pay particular attention to the mechanisms involvi...ng the implementation of neural mechanisms that make use of the temporal structure of neuronal firing, rather than just the average firing rate. 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
Research in the Elizabeth Tucker Lab aims to find treatments that decrease neuroinflammation and improve recovery, as well as to improve morbidity and mortality in patients with infectious neurological diseases. We are currently working with Drs. Sujatha Kannan and Sanjay Jain to study neuroinflammation related to central nervous system tuberculosis – using an animal model to examine the role of neuroinflammation in this disease and how it can differ in developing brains and adult brains. Our team also is working with Dr. Jain to study noninvasive imaging techniques for use in monitoring disease progression and evaluating treatment responses.
Dr. Haughey directs a disease-oriented research program that address questions in basic neurobiology, and clinical neurology. The primary research interests of the laboratory are:
1. To identify biomarkers markers for neurodegenerative diseases including HIV-Associated Neurocognitive Disorders, Multiple Sclerosis, and Alzheimer’s disease. In these studies, blood and cerebral spinal fluid samples obtained from ongoing clinical studies are analyzed for metabolic profiles through a variety of biochemical, mass spectrometry and bioinformatic techniques. These biomarkers can then be used in the diagnosis of disease, as prognostic indicators to predict disease trajectory, or as surrogate markers to track the effectiveness of disease modifying interventions.
2. To better understand how the lipid components of neuronal, and glial membranes interact with proteins to regulate signal transduction associated with differentiation, motility, inflammatory signaling, survival, and neuronal excitab...ility.
3. To understand how extracellular vesicles (exosomes) released from brain resident cells regulate neuronal excitability, neural network activity, and peripheral immune responses to central nervous system damage and infections.
4. To develop small molecule therapeutics that regulate lipid metabolism as a neuroprotective and restorative strategy for neurodegenerative conditions. view less
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.
Our research is focused on understanding the basic mechanisms of programmed cell death in disease pathogenesis. Billions of cells die per day in the human body. Like cell division and differentiation, cell death is also critical for normal development and maintenance of healthy tissues. Apoptosis and other forms of cell death are required for trimming excess, expired and damaged cells. Therefore, many genetically programmed cell suicide pathways have evolved to promote long-term survival of species from yeast to humans. Defective cell death programs cause disease states. Insufficient cell death underlies human cancer and autoimmune disease, while excessive cell death underlies human neurological disorders and aging. Of particular interest to our group are the mechanisms by which Bcl-2 family proteins and other factors regulate programmed cell death, particularly in the nervous system, in cancer and in virus infections. Interestingly, cell death regulators also regulate many other cel...lular processes prior to a death stimulus, including neuronal activity, mitochondrial dynamics and energetics. We study these unknown mechanisms.
We have reported that many insults can trigger cells to activate a cellular death pathway (Nature, 361:739-742, 1993), that several viruses encode proteins to block attempted cell suicide (Proc. Natl. Acad. Sci. 94: 690-694, 1997), that cellular anti-death genes can alter the pathogenesis of virus infections (Nature Med. 5:832-835, 1999) and of genetic diseases (PNAS. 97:13312-7, 2000) reflective of many human disorders. We have shown that anti-apoptotic Bcl-2 family proteins can be converted into killer molecules (Science 278:1966-8, 1997), that Bcl-2 family proteins interact with regulators of caspases and regulators of cell cycle check point activation (Molecular Cell 6:31-40, 2000). In addition, Bcl-2 family proteins have normal physiological roles in regulating mitochondrial fission/fusion and mitochondrial energetics to facilitate neuronal activity in healthy brains. view more
The Joseph Mankowski Lab studies the immunopathogenesis of HIV infection using the SIV/macaque model. Our researchers use a multidisciplinary approach to dissect the mechanism underlying HIV-induced nervous system and cardiac diseases. Additionally, we study the role that host genetics play in HIV-associated cognitive disorders.
Principal Investigator
Joseph L. Mankowski, D.V.M., Ph.D.
Department
Molecular and Comparative Pathobiology
The research in the Kecken Zhang Laboratory is focused on theoretical and computational neuroscience. We use mathematical analysis and computer simulations to study the nervous system at multiple levels, from realistic biophysical models to simplified neuronal networks. Several of our current research projects involve close collaborations with experimental neuroscience laboratories.
Recent advances in molecular and cellular biology, the emergence of more sophisticated animal models of human disease and the development of sensitive, high-resolution imaging systems enable the study of pathophysiology noninvasively in unprecedented detail. The overall goal of our work is to develop new techniques and agents to study human disease through imaging. We concentrate on two areas, i.e., cancer and central nervous system processes. Our work extends from basic chemical and radiochemical synthesis to clinical translation.
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 more
The Mohamed Farah Lab studies axonal regeneration in the peripheral nervous system. We've found that genetic deletion and pharmacological inhibition of beta-amyloid cleaving enzyme (BACE1) markedly accelerate axonal regeneration in the injured peripheral nerves of mice. We postulate that accelerated nerve regeneration is due to blockade of BACE1 cleavage of two different BACE1 substrates. The two candidate substrates are the amyloid precursor protein (APP) in axons and tumor necrosis factor receptor 1 (TNFR1) on macrophages, which infiltrate injured nerves and clear the inhibitory myelin debris. In the coming years, we will systematically explore genetic manipulations of these two substrates in regard to accelerated axonal regeneration and rapid myelin debris removal seen in BACE1 KO mice. We also study axonal sprouting and regeneration in motor neuron disease models.
Neuromyelitis optica (NMO), also known as Devic's disease, is a neuroinflammatory disorder of the optic nerves and spinal cord. Our lab is focused on understanding the pathogenesis of NMO using animal models and cell culture techniques. Recent studies have found an antibody in NMO patients, the NMO-IgG disease, that binds aquaporin-4 (AQP4) found on astrocytes and other cell types.We are trying to understand the relationship of the NMO-IgG to the pathogenesis of NMO. We are also focused on understanding why NMO preferentially attacks the optic nerves and spinal cord. Toward this goal, we found that AQP4 isoforms are differentially expressed on astrocytes in these tissues compared to other tissues in the nervous system (see publications). Aquaporin-4 isoform expression may be critically important in predisposition to disease in NMO.
Researchers in the Pankaj Jay Pasricha Lab are interested in the molecular mechanisms of visceral pain and restoration of enteric neural function with novel strategies, including neural stem cell transplants. Recent research has focused on the enteric nervous system and gut-brain axis, and the complexity of pain in chronic pancreatitis. Another recent study indicates that patients with underlying small intestinal bacterial overgrowth have significant delays in small bowel transit time as compared to those without, while another explored the safety and efficacy of carbon dioxide cryotherapy for treatment of neoplastic Barrett's esophagus.
The Robert Stevens Lab seeks to generate a comprehensive anatomical and functional map of neural injury and repair following incidents such as trauma, stroke, anoxia and sepsis. Several projects have evaluated the relationship between critical illness and central or peripheral nervous system dysfunction. Ongoing projects deploy quantitative brain mapping to probe recovery of consciousness and cognitive function in patients who have experienced acute neurologic insults from trauma, stroke, cardiac arrest and sepsis.
The Ronen Shechter Lab is currently investigating a novel treatment for nerve pain induced by chemotherapy. Our previous research has involved studying the role and mechanism of peripheral opioids as well as the use of dorsal column stimulation to treat pain resulting from a condition affecting the nervous system.
The Seth Blackshaw Lab uses functional genomics and proteomics to rapidly identify the molecular mechanisms that regulate cell specification and survival in both the retina and hypothalamus. We have profiled gene expression in both these tissues, from the start to the end of neurogenesis, characterizing the cellular expression patterns of more than 1,800 differentially expressed transcripts in both tissues. Working together with the lab of Heng Zhu in the Department of Pharmacology, we have also generated a protein microarray comprised of nearly 20,000 unique full-length human proteins, which we use to identify biochemical targets of developmentally important genes of interest.
Information processing in the brain reflects communication among neurons via neurotransmitters. The Solomon Snyder Laboratory studies diverse signaling systems including those of neurotransmitters and second messengers as well as the actions of drugs upon these processes. We are interested in atypical neurotransmitters such as nitric oxide (NO), carbon monoxide (CO), and the D-isomers of certain amino acids, specifically D-serine and D-aspartate. Our discoveries are leading to a better understanding of how certain drugs for Parkinson's disease and Hungtington's disease interact with cells and proteins. Understanding how other second messengers work is giving us insight into anti-cancer therapies.
The Calabresi Lab is located in the department of Neurology at the Johns Hopkins University School of Medicine. Our group investigates why remyelination occasionally fails following central nervous system demyelination in diseases like multiple sclerosis. Our primary focus is on discovering the role of t-cells in promoting or inhibiting myelination by the endogenous glial cells.
The Chen laboratory is interested in understanding the pathogenesis of neurodegenerative disorders, developing diagnostic markers and validating therapeutic targets. The laboratory uses an interdisciplinary approach involving Drosophila model to study the mechanisms underlying neurodegeneration in human central nervous system.
The nervous system has extremely complex RNA processing regulation. Dysfunction of RNA metabolism has emerged to play crucial roles in multiple neurological diseases. Mutations and pathologies of several RNA-binding proteins are found to be associated with neurodegeneration in both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). An alternative RNA-mediated toxicity arises from microsatellite repeat instability in the human genome. The expanded repeat-containing RNAs could potentially induce neuron toxicity by disrupting protein and RNA homeostasis through various mechanisms.
The Sun Lab is interested in deciphering the RNA processing pathways altered by the ALS-causative mutants to uncover the mechanisms of toxicity and molecular basis of cell type-selective vulnerability. Another major focus of the group is to identify small molecule and genetic inhibitors of neuron toxic factors using various high-throughput screening platforms. Finally, we are also highly i...nterested in developing novel CRISPR technique-based therapeutic strategies. We seek to translate the mechanistic findings at molecular level to therapeutic target development to advance treatment options against neurodegenerative diseases. view more
Research in the Vestibular NeuroEngineering Lab (VNEL) focuses on restoring inner ear function through “bionic” electrical stimulation, inner ear gene therapy, and enhancing the central nervous system’s ability to learn ways to use sensory input from a damaged inner ear. VNEL research involves basic and applied neurophysiology, biomedical engineering, clinical investigation and population-based epidemiologic studies. We employ techniques including single-unit electrophysiologic recording; histologic examination; 3-D video-oculography and magnetic scleral search coil measurements of eye movements; microCT; micro MRI; and finite element analysis. Our research subjects include computer models, circuits, animals and humans. For more information about VNEL, click here.
VNEL is currently recruiting subjects for two first-in-human clinical trials:
1) The MVI Multichannel Vestibular Implant Trial involves implantation of a “bionic” inner ear stimulator intended to partially restore sensation... of head movement. Without that sensation, the brain’s image- and posture-stabilizing reflexes fail, so affected individuals suffer difficulty with blurry vision, unsteady walking, chronic dizziness, mental fogginess and a high risk of falling. Based on designs developed and tested successfully in animals over the past the past 15 years at VNEL, the system used in this trial is very similar to a cochlear implant (in fact, future versions could include cochlear electrodes for use in patients who also have hearing loss). Instead of a microphone and cochlear electrodes, it uses gyroscopes to sense head movement, and its electrodes are implanted in the vestibular labyrinth. For more information on the MVI trial, click here.
2) The CGF166 Inner Ear Gene Therapy Trial involves inner ear injection of a genetically engineered DNA sequence intended to restore hearing and balance sensation by creating new sensory cells (called “hair cells”). Performed at VNEL with the support of Novartis and through a collaboration with the University of Kansas and Columbia University, this is the world’s first trial of inner ear gene therapy in human subjects. Individuals with severe or profound hearing loss in both ears are invited to participate. For more information on the CGF166 trial, click here. view more
Principal Investigator
Charles Della Santina, M.D., Ph.D.
Department
Biomedical Engineering
Otolaryngology - Head and Neck Surgery
The goals of the Vikram Chib Lab are to understand how the nervous system organizes the control of movement and how incentives motivate our behaviors. To better understand neurobiological control, our researchers are seeking to understand how motivational cues drive our motor actions. We use an interdisciplinary approach that combines robotics with the fields of neuroscience and economics to examine neuroeconomics and decision making, motion and force control, haptics and motor learning, image-guided surgery and soft-tissue mechanics.
The Agnew Laboratory examines the structure, mechanism and regulation of ion channels that mediate the action potential in nerve and muscle, as well as intracellular calcium concentrations. Much of our work has centered on voltage-activated sodium channels responsible for the inward currents of the action potential. These studies encompass biochemical, molecular biological and biophysical studies of Na channel structure, gating and conductance mechanisms, the stages of channel biosynthesis and assembly, and mechanisms linked to channel neuromodulation.
In recent molecular cloning and expression studies, we have characterized mutations in the human muscle sodium channel that appear to underlie certain inherited myopathies. New studies being pursued in our group also address the questions of structure, receptor properties, and biophysical behavior of intracellular calcium release channels activated by inositol-1,4,5-triphosphate. These channels are expressed at extremely high levels ...in selected cells of the central nervous system, and may play a role in modulating neuronal excitability. view less
In the Zhou Lab, the overall goal of our research is to understand the molecular mechanisms underlying development of the mammalian nervous system. Specifically, we are interested in understanding how neurons generate their complex morphology and form proper circuitries during development and how neurons regenerate to restore connections after brain or spinal cord injuries.
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