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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 lab explores the genetic underpinnings that drive the pathogenesis of a variety of primary central nervous system neoplasms. We are interested in exploiting genetic changes for both diagnostic and therapeutic purposes. Our lab is currently working on understanding the extreme responders and extreme clinical phenotypes of brain and spinal cord tumors to identify factors that may modulate responses to therapy.
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.
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