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.

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, whether defects in cell communication lead to certain hereditary forms of hearing impairment, and if similar mechanisms are related to sound-induced tinnitus.

Led by Dr. Chetan Bettegowda and Dr. Jordina Rincon-Torroella, our lab uses genetic analysis, biomarkers and patient outcome data to identify better ways to diagnose and treat disease. We research a variety of neurological conditions, including central nervous system tumors, trigeminal neuralgia and traumatic brain and spinal injuries.

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 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 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.

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 involving the implementation of neural mechanisms that make use of the temporal structure of neuronal firing, rather than just the average firing rate.

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 illuminate 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.

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.