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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
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
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.
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 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.
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.
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 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
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