A5036772721- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- Epilepsy research and treatment
- Genetics and Neurodevelopmental Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Mitochondrial Function and Pathology
- EEG and Brain-Computer Interfaces
- Anesthesia and Sedative Agents
- Amyotrophic Lateral Sclerosis Research
- Parkinson's Disease Mechanisms and Treatments
- Cholinesterase and Neurodegenerative Diseases
- Ion channel regulation and function
- Genomics and Rare Diseases
- Metabolism and Genetic Disorders
- Nicotinic Acetylcholine Receptors Study
- Bioinformatics and Genomic Networks
- Infectious Encephalopathies and Encephalitis
- Electrochemical Analysis and Applications
- Functional Brain Connectivity Studies
- Drug Transport and Resistance Mechanisms
- Medicinal Plants and Neuroprotection
- Neonatal and fetal brain pathology
- Neural dynamics and brain function
- RNA regulation and disease
- Zebrafish Biomedical Research Applications
University of Alabama at Birmingham
2018-2024
Gladstone Institutes
2021-2024
University of California, San Francisco
2021-2023
Rush University Medical Center
2018-2021
Rush University
2019
Genome-wide association studies identified the
The R47H variant of triggering receptor expressed on myeloid cells 2 (TREM2) increases the risk Alzheimer's disease (AD). To investigate potential mechanisms, we analyzed knockin mice expressing human TREM2-R47H from one mutant mouse Trem2 allele. showed increased seizure activity in response to an acute excitotoxin challenge, compared wildtype controls or common TREM2. also spontaneous thalamocortical epileptiform App amyloid precursor proteins bearing autosomal dominant AD mutations and a...
Inflammatory processes induced by brain injury are important for recovery; however, when uncontrolled, inflammation can be deleterious, likely explaining why most anti-inflammatory treatments have failed to improve neurological outcomes after in clinical trials. In the thalamus, chronic activation of glial cells, a proxy inflammation, has been suggested as an indicator increased seizure risk and cognitive deficits that develop cortical injury. Furthermore, lesions more than other regions,...
Dravet syndrome (DS) is a developmental and epileptic encephalopathy that results from mutations in the Na v 1.1 sodium channel encoded by SCN1A . Most known DS-causing are coding regions of , but we recently identified several disease-associated intron 20 within or near to cryptic evolutionarily conserved “poison” exon, 20N, whose inclusion predicted lead transcript degradation. However, it not clear how these variants alter expression DS pathophysiology an organismal context, nor exon 20N...
Abstract Loss of function progranulin ( GRN ) mutations are a major autosomal dominant cause frontotemporal dementia (FTD). Patients with FTD due to (FTD- develop lobar degeneration TDP-43 pathology type A (FTLD-TDP A) and exhibit elevated levels lysosomal proteins storage material in frontal cortex, perhaps indicating dysfunction as mechanism disease. To investigate whether patients sporadic FTLD similar signs dysfunction, we compared protein levels, transcript FTD- or FTLD-TDP A. We...
Cortical electro-encephalography (EEG) served as the clinical reference for monitoring unconsciousness during general anesthesia. The existing EEG-based monitors classified anesthesia states underdosed, adequate, or overdosed, lacking predictive power due to absence of transition phases among these states. In response this limitation, we undertook an analysis EEG signal isoflurane-induced in mice. Adopting a data-driven approach, applied processing techniques track θ- and δ-band dynamics,...
Tau reduction is a promising therapeutic strategy for Alzheimer's disease. In numerous models, tau via genetic knockout beneficial, at least in part due to protection against hyperexcitability and seizures, but the underlying mechanisms are unclear. Here we describe generation initial study of new conditional
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Abstract Background Genome‐wide association studies have identified genetic risk factors for AD, including a single nucleotide polymorphism in the bridging integrator 1 (BIN1) gene that is present approximately 40% of population and has largest effect size common AD factors. While between BIN1 been established, mechanisms by which contributes to remain understudied. We previously showed increasing expression primary hippocampal neurons increases neuronal excitability (Voskobiynyk & Roth...
Abstract Solute carrier family 6 member 1 ( SLC6A1 ) gene encodes GAT-1, a GABA transporter expressed on glia and presynaptic terminals of inhibitory neurons. Mutations in are associated with myoclonic atonic epilepsy, absence autism, intellectual disability. However, the mechanisms leading to these defects unknown. Here, we used novel mouse model harboring point mutation (S295L) recently identified human that results impaired membrane trafficking GAT-1 protein. We performed chronic wireless...
Abstract Cortical electro-encephalography (EEG) has become the clinical reference for monitoring unconsciousness during general anesthesia. The current EEG-based monitors classify anesthesia states simply as underdosed, adequate, or overdosed, with no transition phases among these states, and therefore predictive power. To address issue of phases, we analyzed EEG signal isoflurane-induced in mice. We adopted a data-driven approach utilized processing to track θ - δ band dynamics well...
Abstract The solute carrier family 6 member 1 ( SLC6A1 ) gene encodes GAT‐1, a γ‐aminobutyric acid transporter expressed on astrocytes and inhibitory neurons. Mutations in are associated with epilepsy developmental disorders, including motor social impairments, but variant‐specific animal models needed to elucidate mechanisms. Here, we report electrocorticographic (ECoG) recordings clinical data from patient variant that GAT‐1 serine‐to‐leucine substitution at amino 295 (S295L), who was...
Alzheimer's disease (AD) affects about five million Americans, who receive only a very modest benefit from current treatment options. Multiple trials have failed in the past, raising interest identifying new targets to treat AD. GWAS studies identified bridging integrator 1 (BIN1) as one of leading genetic risk factors Neurons express unique BIN1 isoforms, and growing body evidence indicates loss neuronal However, function remains unclear its contribution AD is critical investigate. We...
Alzheimer's disease (AD) is marked by the accumulation of Amyloid beta peptides, neuronal cell death, and synapse loss. However, dysregulation voltage gated ion channels may also contribute to AD progression. Our lab has shown that in dorsal hippocampus transgenic mouse models AD, CA1 pyramidal neurons exhibit a channelopathy which hyperpolarization-activated cyclic-nucleotide (HCN) are mislocalized. magnetic resonance imaging (MRI) studies have anterior hippocampus, corresponding ventral...
Genome-wide association studies identified the BIN1 locus as a leading modulator of genetic risk in Alzheimer’s disease (AD). One limitation understanding ’s contribution to AD is its unknown function brain. AD-associated variants are generally noncoding and likely change expression. Here, we determined effects increasing expression major neuronal isoform human cultured hippocampal neurons. Higher induced network hyperexcitability on multielectrode arrays, increased frequency synaptic...
Abstract Dravet syndrome (DS) is a developmental and epileptic encephalopathy that results from mutations in the Na v 1.1 sodium channel encoded by SCN1A . Most known DS-causing are coding regions of , but we recently identified several disease-associated intron 20 within or near to cryptic evolutionarily conserved “poison” exon, 20N, whose inclusion leads transcript degradation. However, it not clear how these variants alter processing DS pathophysiology an organismal context, nor exon 20N...
Abstract Background Alzheimer’s disease (AD) affects about five million Americans and the underlying causes of remain uncertain. Genome wide association studies (GWAS) have identified bridging integrator 1 ( BIN1 ) as one leading genetic risk factors in AD. Neurons express unique isoforms, but their function is unknown. Thus, key question that may contribute to a deeper understanding AD pathophysiology how neuronal function. Methods To address this question, we determined effects expressing...
Abstract Background Loss‐of‐function mutations in progranulin ( GRN ) are an autosomal dominant cause of frontotemporal dementia (FTD). Progranulin is critical for maintenance lysosomal function. Patients with FTD due to (FTD‐ exhibit signs dysfunction, which may contribute FTD‐ pathogenesis. To assess the potential involvement dysfunction sporadic origin, we investigated whether abnormalities also present patients lobar degeneration TDP‐43 pathology (FTLD‐TDP) type A, same FTLD subtype...