A5075094672- Neurobiology and Insect Physiology Research
- Ion Channels and Receptors
- Ion channel regulation and function
- Olfactory and Sensory Function Studies
- Hereditary Neurological Disorders
- Hearing, Cochlea, Tinnitus, Genetics
- Echinoderm biology and ecology
- Neurogenesis and neuroplasticity mechanisms
- Circadian rhythm and melatonin
- Aquatic life and conservation
- Aquaculture Nutrition and Growth
- Hearing Loss and Rehabilitation
- Connexins and lens biology
- Toxin Mechanisms and Immunotoxins
- Noise Effects and Management
- Crustacean biology and ecology
- Photoreceptor and optogenetics research
- Zebrafish Biomedical Research Applications
- Coral and Marine Ecosystems Studies
- Cannabis and Cannabinoid Research
- Bioactive Compounds and Antitumor Agents
- Marine and coastal ecosystems
- Aquatic Ecosystems and Biodiversity
- Coenzyme Q10 studies and effects
- Insect Pheromone Research and Control
Johns Hopkins University
1993-2024
Johns Hopkins Medicine
2014-2024
Harvard University
2015
University of Washington
2015
Stanford Health Care
2015
SUNY College of Environmental Science and Forestry
2015
State University of New York
2015
York University
2015
University of Baltimore
2014
University of Bamako
2012
Abstract Crosstalk between ion channels and small GTPases is critical during homeostasis disease, but little known about the structural underpinnings of these interactions. TRPV4 a polymodal, calcium-permeable cation channel that has emerged as potential therapeutic target in multiple conditions. Gain-of-function mutations also cause hereditary neuromuscular disease. Here, we present cryo-EM structures human complex with RhoA ligand-free, antagonist-bound closed, agonist-bound open states....
Blood-CNS barrier disruption is a hallmark of numerous neurological disorders, yet whether breakdown sufficient to trigger neurodegenerative disease remains unresolved. Therapeutic strategies mitigate hyperpermeability are also limited. Dominant missense mutations the cation channel transient receptor potential vanilloid 4 (TRPV4) cause forms hereditary motor neuron disease. To gain insights into cellular basis these we generated knock-in mouse models TRPV4 channelopathy by introducing two...
Abstract The cation channel transient receptor potential vanilloid 4 (TRPV4) is one of the few identified ion channels that can directly cause inherited neurodegeneration syndromes, but molecular mechanisms are unknown. Here, we show in vivo expression a neuropathy-causing TRPV4 mutant (TRPV4 R269C ) causes dose-dependent neuronal dysfunction and axonal degeneration, which rescued by genetic or pharmacological blockade activity. triggers increased intracellular Ca 2+ through...
Abstract Adult neurogenesis, the generation of new neurons from adult precursor cells, occurs in brains a phylogenetically diverse array animals. In higher (amniotic) vertebrates, these cells are glial that reside within specialized regions, known as neurogenic niches , elements which both support and regulate neurogenesis. The vivo identity location responsible for neurogenesis nonvertebrate taxa, however, remain largely unknown. Among invertebrates, has been particularly well characterized...
Transplantation of exogenous stem cells has been proposed as a treatment to prevent or reverse sensorineural hearing loss. Here, we investigate the effects transplantation adult human olfactory mucosa-derived on auditory function in A/J mice, strain exhibiting early-onset progressive Recent evidence indicates that these exhibit multipotency settings and may represent subtype mesenchymal cell. Olfactory were injected into cochleae mice via lateral wall cochleostomy during time period which...
Abstract TRPV4 is a cell surface-expressed calcium-permeable cation channel that mediates cell-specific effects on cellular morphology and function. Dominant missense mutations of cause distinct, tissue-specific diseases, but the pathogenic mechanisms are unknown. Mutations causing peripheral neuropathy localize to intracellular N-terminal domain whereas skeletal dysplasia in multiple domains. Using an unbiased screen, we identified cytoskeletal remodeling GTPase RhoA as interactor....
Abstract The olfactory and accessory lobes of eureptantian decapod crustaceans are bilateral brain neuropil regions located within the deutocerebrum. Although lobe seems to receive only primary inputs, receives higher‐order multimodal (including olfactory) inputs. output pathways from both provided by axons a large population projection neurons, whose somata lie adjacent lobes. these neurons form tract that projects bilaterally medulla terminalis hemiellipsoid body in lateral protocerebrum....
Mitotically active regions persist in the brains of decapod crustaceans throughout their lifetimes, as they do many vertebrates. The most well-studied these decapods occurs within a soma cluster, known cluster 10, located deutocerebrum. Cluster 10 crayfish and lobsters is composed somata two anatomically functionally distinct classes projection neurons: olfactory lobe (OL) neurons accessory (AL) neurons. While adult-generated cells survive for at least year, final phenotypes remain unknown....
Freshwater crayfish have three known photoreceptive systems: the compound eyes, extraretinal brain photoreceptors, and caudal photoreceptors. The primary goal of work described here was to explore contribution photoreceptors circadian locomotory activity define some underlying neural pathways. Immunocytochemical studies in parastacid (southern hemisphere) Cherax destructor reveal their expression blue light-sensitive photopigment cryptochrome neurotransmitter histamine. project two small...
Adult taste buds are maintained by the lifelong proliferation of epithelial stem and progenitor cells, identities which have remained elusive. It has been proposed that these cells reside either within bud (intragemmal) or in surrounding epithelium (perigemmal). Here, we apply three different vivo approaches enabling single-cell resolution proliferative history to identify putative associated with adult mouse buds. Experiments were performed across circadian peak oral (04:00 h), a time...
Abstract Output from the olfactory lobe (primary center) of eumalacostracan crustaceans is transmitted to medulla terminalis (MT) and hemiellipsoid body (HB) in lateral protocerebrum (higher order by a large population projection neurons. In eureptantian (lobsters, crayfish, crabs), these neurons also form output pathway an additional neuropil, accessory center), which appears have arisen de novo animals. previous study lobsters crayfish we showed that whereas innervating project primarily...
Information about the input and output pathways of higher-order brain neuropils is essential for gaining an understanding their functions. The present study examines connectivity two in central olfactory pathway crayfish: accessory lobe its target neuropil, hemiellipsoid body. It known that subregions lobe, cortex medulla, receive different inputs; medulla receives visual tactile inputs, whereas neither (Sandeman et al. [1995] J Comp Neurol 352:263–279). By using dye injections into we...
Mutations in over 50 genes have been associated with Charcot-Marie-Tooth (CMT) disease. As new continue to be discovered, the task of sequencing each them individually traditional techniques becomes increasingly burdensome. In addition, these approaches disadvantages that may
Abstract Background Auditory brainstem responses (ABRs) are used to study auditory acuity in animal-based medical research. ABRs evoked by acoustic stimuli, and consist of an electrical signal resulting from summated activity the nerve nuclei. ABR analysis determines sound intensity at which a neural response first appears (hearing threshold). Traditionally, threshold has been assessed visual estimation series different intensities. Here we develop automated detection method that eliminates...
To characterize 2 novel TRPV4 mutations in unrelated families exhibiting the Charcot-Marie-Tooth disease type 2C (CMT2C) phenotype.Direct CMT gene testing was performed on with CMT2C. A 4-fold symmetric tetramer model of human generated to map locations these relative previously identified disease-causing (neuropathy, skeletal dysplasia, and osteoarthropathy). Effects expression, localization, channel activity were determined by immunocytochemical, immunoblotting, Ca(2+) imaging,...
Serotonin depletion during embryogenesis has been shown previously to retard the growth of olfactory and accessory lobes lobster deutocerebrum (Benton et al., 1997). The present study was undertaken determine whether morphological changes in interneurons innervating these contribute this retardation. We examined effects vivo serotonin using 5,7-dihydroxytryptamine (5,7-DHT) on morphology projection neurons, one two major classes that innervate both lobes. Intracellular dye fills neurons...
Notch signaling is a highly conserved intercellular pathway with tightly regulated and pleiotropic roles in normal tissue development homeostasis. Dysregulated has also been implicated human disease, including multiple forms of cancer, represents an emerging therapeutic target. Successful such therapeutics requires detailed understanding potential on-target toxicities. Here, we identify autosomal dominant mutations the canonical ligand Jagged1 (or JAG1) as cause peripheral nerve disease 2...
Ubiquitin (Ub)-mediated regulation of plasmalemmal ion channel activity canonically occurs via stimulation endocytosis. Whether ubiquitination can modulate by alternative mechanisms remains unknown. Here, we show that the transient receptor potential vanilloid 4 (TRPV4) cation is multiubiquitinated within its cytosolic N-terminal and C-terminal intrinsically disordered regions (IDRs). Mutagenizing select lysine residues to block but not IDR resulted in a marked elevation TRPV4-mediated...
A life-long turnover of sensory and interneuronal populations has been documented in the olfactory pathways both vertebrates invertebrates, creating a situation where axons new afferent must insert into highly specialized glomerular neuropil. dense serotonergic innervation primary processing areas these neurons synapse also is consistent feature across species. Prior studies lobsters have shown that serotonin promotes branching projection neurons. This paper presents evidence regulates...
Abstract The main output pathways from the olfactory lobes (primary centers) and accessory (higher‐order integrative areas) of decapod crustaceans terminate within both neuropil regions lateral protocerebrum: medulla terminalis hemiellipsoid body. present study examines morphogenesis protocerebral neuropils lobster, Homarus americanus , development their neuronal connections with paired lobes. was found to emerge during initial stages embryogenesis be target pathway lobe. In contrast, body...
Objective Myotonia is caused by involuntary firing of skeletal muscle action potentials and causes debilitating stiffness. Current treatments are insufficiently efficacious associated with side effects. can be triggered voluntary movement (electrically induced myotonia) or percussion (mechanically myotonia). Whether distinct molecular mechanisms underlie these triggers unknown. Our goal was to identify ion channels involved in mechanically myotonia evaluate block the as a novel approach...