A5013146806- Neuroscience and Neuropharmacology Research
- Amino Acid Enzymes and Metabolism
- Epigenetics and DNA Methylation
- Tryptophan and brain disorders
- Ion channel regulation and function
- Receptor Mechanisms and Signaling
- Endoplasmic Reticulum Stress and Disease
- Amyotrophic Lateral Sclerosis Research
- Anesthesia and Neurotoxicity Research
- Fibroblast Growth Factor Research
- Heat shock proteins research
- Cholinesterase and Neurodegenerative Diseases
- Neurogenesis and neuroplasticity mechanisms
- Alzheimer's disease research and treatments
- Neurogenetic and Muscular Disorders Research
- Genetics and Neurodevelopmental Disorders
- Protein Kinase Regulation and GTPase Signaling
- Neural dynamics and brain function
- Sex and Gender in Healthcare
- Hippo pathway signaling and YAP/TAZ
- Genetics, Aging, and Longevity in Model Organisms
- Nicotinic Acetylcholine Receptors Study
- Ion Channels and Receptors
- Health Policy Implementation Science
- S100 Proteins and Annexins
McLean Hospital
2020-2024
Harvard University
2020-2024
The University of Texas Medical Branch at Galveston
2013-2020
d -serine is the primary NMDAR coagonist at mature forebrain synapses and synthesized by enzyme serine racemase (SR). However, our understanding of mechanisms regulating availability synaptic remains limited. Though early studies suggested released from astrocytes, more recent have demonstrated a predominantly neuronal localization SR. More specifically, work intriguingly suggests that SR may be found postsynaptic density, yet functional implications on transmission are not known. Here, we...
Resilience and vulnerability to neuropsychiatric disorders are linked molecular changes underlying excitability that still poorly understood. Here, we identify glycogen-synthase kinase 3β (GSK3β) voltage-gated Na+ channel Nav1.6 as regulators of neuroplasticity induced by environmentally enriched (EC) or isolated (IC) conditions-models for resilience vulnerability. Transcriptomic studies in the nucleus accumbens from EC IC rats predicted low levels GSK3β SCN8A mRNA a protective phenotype...
Purpose: Retinal ischemia, a common cause of several vision-threatening diseases, contributes to the death retinal neurons, particularly ganglion cells (RGCs). Heat shock transcription factor 1 (HSF1), stress-responsive protein, has been shown be important in response cellular stress stimuli, including ischemia. This study is investigate whether HSF1 role neuronal injury mouse model ischemia-reperfusion (IR). Methods: IR was induced by inserting an infusion needle into anterior chamber right...
Abstract Synaptic damage is one of the most prevalent pathophysiological responses to traumatic CNS injury and underlies much associated cognitive dysfunction; however, it poorly understood. The D‐amino acid, D‐serine, serves as primary co‐agonist at synaptic NMDA receptors (NDMARs) a critical mediator NMDAR‐dependent transmission plasticity. In physiological conditions, D‐serine produced released by neurons from enzymatic conversion L‐serine serine racemase (SRR). However, under...
Abstract Background Mutations in the Cu/Zn superoxide dismutase gene (SOD1) are responsible for 20% of familial forms amyotrophic lateral sclerosis (ALS), and mutant SOD1 has been shown to have increased surface hydrophobicity vitro . Mutant may adopt a complex array conformations with varying toxicity vivo We used novel florescence-based proteomic assay using 4,4’-bis-1-anilinonaphthalene-8-sulfonate (bisANS) assess hydrophobicity, thereby distinguish between different conformations,...
Protein–protein interactions (PPI) offer unexploited opportunities for CNS drug discovery and neurochemical probe development. Here, we present ZL181, a novel peptidomimetic targeting the PPI interface of voltage-gated Na+ channel Nav1.6 its regulatory protein fibroblast growth factor 14 (FGF14). ZL181 binds to FGF14 inhibits interaction with C-tail. In HEK-Nav1.6 expressing cells, acts synergistically suppress current density slow kinetics fast inactivation, but antagonizes modulation...
Abnormalities in electroencephalographic (EEG) biomarkers occur patients with schizophrenia and those clinically at high risk for transition to psychosis are associated cognitive impairment. Converging evidence suggests N-methyl-D-aspartate receptor (NMDAR) hypofunction plays a central role the pathophysiology of likely contributes biomarker impairments. Thus, characterizing these is significant interest early diagnosis development novel treatments. We utilized vivo EEG recordings behavioral...
TAR DNA binding protein 43 (TDP‐43) is a nuclear that has been shown to have altered homeostasis in the form of neuronal and cytoplasmic aggregates some familial almost all cases sporadic amyotrophic lateral sclerosis as well 51% frontotemporal lobar degeneration 57% Alzheimer's disease cases. Heat shock proteins (HSPs), such HSP70, recognize misfolded or aggregated refold, disaggregate, turn them over are upregulated by master transcription factor heat 1 (HSF1). Here, we explore effect HSF1...
Multiple voltage-gated Na+ (Nav) channelopathies can be ascribed to subtle changes in the Nav macromolecular complex. Fibroblast growth factor 14 (FGF14) is a functionally relevant component of Nav1.6 channel complex, causative link spinocerebellar ataxia 27 (SCA27) and an emerging risk for neuropsychiatric disorders. Yet, how this protein:channel complex regulated cell still poorly understood. To search key cellular pathways upstream FGF14:Nav1.6 we have developed, miniaturized optimized...
Abstract The proper development and function of telencephalic GABAergic interneurons is critical for maintaining the excitation inhibition (E/I) balance in cortical circuits. Glutamate contributes to interneuron (CIN) via N -methyl- d -aspartate receptors (NMDARs). NMDAR activation requires binding a co-agonist, either glycine or -serine. -serine (co-agonist at many mature forebrain synapses) racemized by neuronal enzyme serine racemase (SR) from l We utilized constitutive SR knockout (SR...
Abstract D-serine is the primary NMDA receptor (NMDAR) co-agonist at mature forebrain synapses and synthesized by enzyme serine racemase (SR). However, our understanding of mechanisms regulating availability synaptic remains limited. Though early studies suggested released from astrocytes, more recent have demonstrated a predominantly neuronal localization SR. More specifically, work intriguingly suggests that SR may be found postsynaptic density, yet functional implications on transmission...
SUMMARY Cognitive losses resulting from severe brain trauma have long been associated with the focal region of tissue damage, leading to devastating functional impairment. For decades, researchers focused on sequelae cellular alterations that exist within perilesional tissues; however, few clinical trials successful. Here, we employed a mouse injury model resulted in expansive synaptic damage regions outside injury. Our findings demonstrate results prolonged increase D-serine release...
The expression of GABA A Rs goes through large scale, evolutionarily conserved changes the early postnatal period. While these have been well-studied in brain regions such as hippocampus and sensory cortices, less is known about developmental other areas. nucleus accumbens (NAc) a major hub circuitry that mediates motivated behaviors disruptions NAc activity part neuropathology observed mood substance use disorders. Considering importance vulnerability to etiology disorders, it essential...
Background Neurodevelopmental disorders (NDDs) can cause debilitating impairments in social cognition and aberrant functional connectivity large-scale brain networks, leading to isolation diminished everyday functioning. To facilitate the treatment of impairments, animal models NDDs that link N- methyl-D-aspartate receptor (NMDAR) hypofunction deficits adulthood have been used. However, understanding etiology requires investigating changes during sensitive windows development. Methods We...
ABSTRACT Introduction Abnormalities in electroencephalographic (EEG) biomarkers occur patients with schizophrenia and those clinically at high risk for transition to psychosis are associated cognitive impairment. While the pathophysiology of remains poorly understood, converging evidence suggests N -methyl-D-aspartate receptor (NMDAR) hypofunction plays a central role likely contributes biomarker impairments. Thus, characterization such is significant interest both early diagnosis...