A5048476893- Alzheimer's disease research and treatments
- Tryptophan and brain disorders
- Neuroscience and Neuropharmacology Research
- Mitochondrial Function and Pathology
- Receptor Mechanisms and Signaling
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Ion channel regulation and function
- Computational Drug Discovery Methods
- Biotin and Related Studies
- Stress Responses and Cortisol
- Bioinformatics and Genomic Networks
- Cholinesterase and Neurodegenerative Diseases
- Dementia and Cognitive Impairment Research
- Nutritional Studies and Diet
- Metabolomics and Mass Spectrometry Studies
- Diet and metabolism studies
Emory University
2020-2024
Mayo Clinic in Florida
2024
Emory and Henry College
2022
University of Florida
2019
Alzheimer's disease (AD) lacks protein biomarkers reflective of its diverse underlying pathophysiology, hindering diagnostic and therapeutic advancements. Here, we used integrative proteomics to identify cerebrospinal fluid (CSF) representing a wide spectrum AD pathophysiology. Multiplex mass spectrometry identified ~3500 ~12,000 proteins in CSF brain, respectively. Network analysis the brain proteome resolved 44 biologically modules, 15 which overlapped with proteome. markers these...
The molecular mechanisms and pathways enabling certain individuals to remain cognitively normal despite high levels of Alzheimer's disease (AD) pathology incompletely understood. These people with AD are described as preclinical or asymptomatic (AsymAD) appear exhibit cognitive resilience the clinical manifestations dementia. Here we present a comprehensive network-based approach from cases clinically pathologically defined map resilience-associated extend mechanistic validation. Multiplex...
Psychosocial experiences affect brain health and aging trajectories, but the molecular pathways underlying these associations remain unclear. Normal function relies on energy transformation by mitochondria oxidative phosphorylation (OxPhos). Two main lines of evidence position both as targets drivers psychosocial experiences. On one hand, chronic stress exposure mood states may alter multiple aspects mitochondrial biology; other functional variations in OxPhos capacity social behavior,...
Proteomic studies utilizing postmortem human brain tissue samples have yielded robust assessments of the aging and neurodegenerative disease(s) proteomes. While these analyses provide lists molecular alterations in conditions, like Alzheimer’s disease (AD), identifying individual proteins that affect biological processes remains a challenge. To complicate matters, protein targets may be highly understudied limited information on their function. address hurdles, we sought to establish...
Posttranslational modifications (PTMs) such as phosphorylation of RNA-binding proteins (RBPs) regulate several critical steps in RNA metabolism, including spliceosome assembly, alternative splicing, and mRNA export. Notably, serine-/arginine- (SR)-rich RBPs are densely phosphorylated compared with the remainder proteome. Previously, we showed that dephosphorylation splicing factor SRSF2 regulated increased interactions similar arginine-rich U1-70K LUC7L3. However, large-scale functional...
There is an urgent need to improve the translational validity of Alzheimer's disease (AD) mouse models. Introducing genetic background diversity in AD models has been proposed as a way increase and enable discovery previously uncharacterized contributions susceptibility or resilience. However, extent which influences brain proteome its perturbation unknown. In this study, we crossed 5XFAD model on C57BL/6J (B6) inbred with DBA/2J (D2) analyzed effects variation F1 progeny. Both transgene...
RGS14 is a complex multifunctional scaffolding protein that highly enriched within pyramidal cells (PCs) of hippocampal area CA2. In these neurons, suppresses glutamate-induced calcium influx and related G ERK signaling in dendritic spines to restrain postsynaptic plasticity. Previous findings show that, unlike PCs areas CA1 CA3, CA2 are resistant number neurological insults, including degeneration caused by temporal lobe epilepsy (TLE). While protective against peripheral injury, similar...
RGS14 is a complex multifunctional scaffolding protein that highly enriched within pyramidal cells (PCs) of hippocampal area CA2. There, suppresses glutamate-induced calcium influx and related G ERK signaling in dendritic spines to restrain postsynaptic plasticity. Previous findings show that, unlike PCs areas CA1 CA3, CA2 are resistant number neurological insults, including degeneration caused by temporal lobe epilepsy (TLE). While protective against peripheral injury, similar roles for...
Abstract Introduction African Americans (AA) are widely underrepresented in plasma biomarker studies for Alzheimer’s disease (AD) and current diagnostic candidates do not reflect the heterogeneity of AD. Methods Untargeted proteome measurements were obtained using SomaScan 7k platform to identify novel biomarkers AD a cohort AA clinically diagnosed as dementia (n=183) or cognitively unimpaired (CU, n=145). Machine learning approaches implemented set proteins that yields best classification...
There is a pressing need to improve the translational validity of Alzheimer's disease (AD) mouse models. Introducing genetic background diversity in AD models has been proposed as way increase and enable discovery previously uncharacterized contributions susceptibility or resilience. However, extent which influences brain proteome its perturbation unknown. Here we crossed 5XFAD model on C57BL/6J (B6) inbred with DBA/2J (D2) analyzed effects variation F1 progeny. Both transgene insertion...
Abstract We present an integrative proteomic strategy for the nomination and validation of proteins associated with cognitive resilience to Alzheimer’s disease (AD). Correlation network analysis across distinct stages AD was used prioritize protein modules linked resilience. Neuritin (NRN1), a hub in module synaptic biology, identified as top candidate selected functional cultured neurons. NRN1 provided dendritic spine against amyloid-β (Aβ), blocked Aβ-induced neuronal hyperexcitability....
Abstract Psychosocial experiences affect brain health and aging trajectories, but the molecular pathways underlying these associations remain unclear. Normal function relies heavily on energy transformation by mitochondria oxidative phosphorylation (OxPhos), two main lines of evidence bi-directionally link as both targets drivers psychosocial experiences. On one hand, chronic stress exposure possibly mood states alter multiple aspects mitochondrial biology; other functional variations in...
Abstract Background The noradrenergic locus coeruleus (LC) is the first region to accumulate hyperphosphorylated tau pathology (p‐tau) in Alzheimer’s disease (AD). Using TgF344‐AD transgenic rats, which develop endogenous p‐tau LC prior forebrain regions, we have recently demonstrated age‐dependent effects of on firing rates. Specifically, neurons exhibit early hyperactivity followed by late hypoactivity. These changes rates are coincident with emergence behavioral phenotypes that...
ABSTRACT Post-translational modifications (PTMs) within splicing factor RNA-binding proteins (RBPs), such as phosphorylation, regulate several critical steps in RNA metabolism including spliceosome assembly, alternative and mRNA export. Notably, the arginine-/serine-rich (RS) domains SR are densely modified by phosphorylation compared with remainder of proteome. Previously, we showed that dephosphorylation SRSF2 regulated increased interactions similar arginine-rich RBPs U1-70K LUC7L3. In...