A5032814145- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Neuroscience and Neural Engineering
- Lipid Membrane Structure and Behavior
- Molecular Sensors and Ion Detection
- Hemoglobinopathies and Related Disorders
- Erythrocyte Function and Pathophysiology
- Epilepsy research and treatment
- Force Microscopy Techniques and Applications
- Acoustic Wave Resonator Technologies
- Nerve injury and regeneration
- Blood properties and coagulation
- Cellular transport and secretion
- Cardiac electrophysiology and arrhythmias
- Blood groups and transfusion
- Cellular Mechanics and Interactions
- Mechanical and Optical Resonators
- Pancreatic function and diabetes
- Genetics and Neurodevelopmental Disorders
Tufts University
2020-2023
AstraZeneca (United States)
2020
University of Connecticut
2014-2017
Super-resolution microscopy recently revealed that, unlike the soma and dendrites, axon membrane skeleton is structured as a series of actin rings connected by spectrin filaments that are held under tension. Currently, structure-function relationship axonal structure unclear. Here, we used atomic force (AFM) to show stiffness plasma significantly higher than stiffnesses dendrites somata. To examine whether determines its overall stiffness, introduced coarse-grain molecular dynamics model...
Hyperpolarizing GABAAR currents, the unitary events that underlie synaptic inhibition, are dependent upon efficient Cl− extrusion, a process is facilitated by neuronal specific K+/Cl− co-transporter KCC2. Its activity also determinant of anticonvulsant efficacy canonical GABAAR-positive allosteric: benzodiazepines (BDZs). Compromised KCC2 implicated in pathophysiology status epilepticus (SE), medical emergency rapidly becomes refractory to BDZ (BDZ-RSE). Here, we have identified small...
Kcc2 plays a critical role in determining the efficacy of synaptic inhibition, however, cellular mechanism neurons use to regulate its membrane trafficking, stability and activity are ill-defined. To address these issues, we used affinity purification isolate stable multi-protein complexes from plasma murine forebrain. We resolved using Blue-native polyacrylamide gel electrophoresis (BN-PAGE) coupled LC-MS/MS label-free quantification. Data available via ProteomeXchange with identifier...
First-in-line benzodiazepine treatment fails to terminate seizures in about 30% of epilepsy patients, highlighting a need for novel anti-seizure strategies. It is emerging that impaired K+/Cl- cotransporter 2 (KCC2) activity leads deficits GABAergic inhibition and increased seizure vulnerability patients. In neurons, the with-no-lysine (WNK) kinase-STE20/SPS1-related proline/alanine-rich (SPAK) kinase signalling pathway inhibits KCC2 via T1007 phosphorylation. Here, we exploit selective WNK...
Small conductance calcium-activated potassium (KCa2) channels are expressed throughout the CNS and play a critical role in synaptic neuronal excitability. KCa2 have somatodendritic distribution with their highest expression distal dendrites. It is unclear whether specifically present on axon initial segment (AIS), site at which action potentials initiated neurons. Through powerful combination of toxin pharmacology, single-molecule atomic force microscopy, dual-color fluorescence we report...
ABSTRACT KCC2 plays a critical role in determining the efficacy of synaptic inhibition and deficits its activity lead to epilepsy neurodevelopmental delay. Here we use unbiased proteomic analyses demonstrate that forms stable protein complexes neuronal plasma membrane with 96 autism and/or risk gene (ASD/Epi) products including ANKB, ANKG, CNTN1, ITPR1, NCKAP1, SCN2A, SHANK3, SPTAN1, SPTBN1. Many these proteins are also targets Fragile-X mental retardation (FMRP), inactivation which is...
ABSTRACT Kcc2 plays a critical role in determining the efficacy of synaptic inhibition, however, cellular mechanism neurons use to regulate its membrane trafficking, stability and activity are ill-defined. To address these issues, we used affinity purification isolate stable multi-protein complexes from plasma murine forebrain. We resolved using Blue-native polyacrylamide gel electrophoresis (BN-PAGE) coupled LC-MS/MS. Purified migrated as distinct molecular species 300, 600 800 kDa...