A5102961083- Alzheimer's disease research and treatments
- Bioinformatics and Genomic Networks
- Genetic Associations and Epidemiology
- Neuroinflammation and Neurodegeneration Mechanisms
- Folate and B Vitamins Research
- Epigenetics and DNA Methylation
- Nutrition, Genetics, and Disease
- Dementia and Cognitive Impairment Research
- Parkinson's Disease Mechanisms and Treatments
- Biological Research and Disease Studies
- RNA regulation and disease
- Single-cell and spatial transcriptomics
- Health, Environment, Cognitive Aging
- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Intracerebral and Subarachnoid Hemorrhage Research
- Mitochondrial Function and Pathology
- Nuclear Receptors and Signaling
- Inflammation biomarkers and pathways
- Neurological diseases and metabolism
- Gene expression and cancer classification
- RNA Research and Splicing
- Immune cells in cancer
- Neurological Disease Mechanisms and Treatments
- Genomic variations and chromosomal abnormalities
Genomics England
2024-2025
Mayo Clinic in Florida
2015-2024
WinnMed
2013-2024
The University of Texas Southwestern Medical Center
2024
Jacksonville College
2011-2024
California Polytechnic State University
2024
Celyad (Belgium)
2023
Mount Sinai Medical Center
2017
Mayo Clinic in Arizona
2017
Medical University of Silesia
2015
Abstract Previous genome-wide association studies (GWAS), conducted by our group and others, have identified loci that harbor risk variants for neurodegenerative diseases, including Alzheimer's disease (AD). Human are enriched polymorphisms affect gene expression, some known to associate with expression changes in the brain. Postulating many confer via transcriptional regulatory mechanisms, we analyzed levels brain tissue of subjects AD related diseases. Herein, describe collective datasets...
Abstract Introduction Comparative transcriptome analyses in Alzheimer's disease (AD) and other neurodegenerative proteinopathies can uncover both shared distinct pathways. Methods We analyzed 940 brain transcriptomes including patients with AD, progressive supranuclear palsy (PSP; a primary tauopathy), control subjects. Results identified transcriptional coexpression networks implicated myelination, which were lower PSP temporal cortex (TCX) compared AD. Some of these associations retained...
Abstract Introduction MAPT encodes for tau, the predominant component of neurofibrillary tangles that are neuropathological hallmarks Alzheimer’s disease (AD). Genetic association variants with late-onset AD (LOAD) risk has been inconsistent, although insufficient power and incomplete assessment haplotypes may account this. Methods We examined LOAD in more than 20,000 subjects ( n -cases = 9,814, -controls 11,550) from Mayo Clinic 2,052, 3,406) Disease Genetics Consortium (ADGC, 7,762,...
Rare coding variants ABI3_rs616338-T and PLCG2_rs72824905-G were identified as risk or protective factors, respectively, for Alzheimer's disease (AD).We tested the association of these with five neurodegenerative diseases in Caucasian case-control cohorts: 2742 AD, 231 progressive supranuclear palsy (PSP), 838 Parkinson's (PD), 306 dementia Lewy bodies (DLB) 150 multiple system atrophy (MSA) vs. 3351 controls; an African-American AD cohort (181 331 controls). 1479 1491 controls...
Abstract To uncover molecular changes underlying blood-brain-barrier dysfunction in Alzheimer’s disease, we performed single nucleus RNA sequencing 24 disease and control brains focused on vascular astrocyte clusters as main cell types of gliovascular-unit. The majority the transcriptional were pericytes. Of targets predicted to interact with astrocytic ligands, SMAD3 , upregulated pericytes, has highest number ligands including VEGFA downregulated astrocytes. We validated these findings...
To investigate the top late-onset Alzheimer disease (LOAD) risk loci detected or confirmed by International Genomics of Alzheimer's Project for association with brain gene expression levels to identify variants that influence (AD) through regulation.Expression from cerebellum (CER) and temporal cortex (TCX) were obtained using Illumina whole-genome cDNA-mediated annealing, selection, extension, ligation assay (WG-DASL) ∼400 autopsied patients (∼200 AD ∼200 non-AD pathologies). We tested 12...
Large-scale brain bulk-RNAseq studies identified molecular pathways implicated in Alzheimer's disease (AD), however these findings can be confounded by cellular composition changes bulk-tissue. To identify cell intrinsic gene expression alterations of individual types, we designed a bioinformatics pipeline and analyzed three AD control datasets temporal dorsolateral prefrontal cortex from 685 samples. We detected cell-proportion brains that are robustly replicable across the independently...
Abstract Background Alzheimer’s disease (AD) is neuropathologically characterized by amyloid-beta (Aβ) plaques and neurofibrillary tangles. The main protein components of these hallmarks include Aβ40, Aβ42, tau, phosphor-tau, APOE. We hypothesize that genetic variants influence the levels solubility AD-related proteins in brain; identifying may provide key insights into pathogenesis. Methods Genome-wide genotypes were collected from 441 AD cases, imputed to haplotype reference consortium...
Progressive supranuclear palsy (PSP) is a neurodegenerative parkinsonian disorder characterized by tau pathology in neurons and glial cells. Transcriptional regulation has been implicated as potential mechanism conferring disease risk neuropathology for some PSP genetic variants. However, the role of transcriptional changes drivers distinct cell-specific lesions not explored. In this study, we integrated brain gene expression measurements, quantitative traits genome-wide genotypes from 268...
To investigate association of genetic risk factors for late-onset Alzheimer disease (LOAD) with posterior cortical atrophy (PCA), a syndrome visual impairment predominant (AD) pathology in regions, and "posterior AD" neuropathology.We assessed 81 participants PCA diagnosed clinically 54 neuropathologic diagnosis AD vs 2,523 controls 11 significant single nucleotide polymorphisms (SNPs) from published LOAD genome-wide studies.There was highly APOE ε4 increased (p = 0.0003, odds ratio [OR]...
Abstract INTRODUCTION Multi-omics studies in Alzheimer’s disease (AD) revealed many potential pathways and therapeutic targets. Despite their promise of precision medicine, these lacked African Americans (AA) Latin (LA), who are disproportionately affected by AD. METHODS To bridge this gap, Accelerating Medicines Partnership AD (AMP-AD) expanded brain multi-omics profiling to multi-ethnic donors. RESULTS We generated data curated harmonized phenotypic from AA (n=306), LA (n=326), or (n=4)...
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, yet our comprehension predominantly relies on studies within non-Hispanic White (NHW) population. Here we aimed to provide comprehensive insights into proteomic landscape of AD across diverse racial and ethnic groups.
Abstract INTRODUCTION Multi‐omics studies in Alzheimer's disease (AD) revealed many potential pathways and therapeutic targets. Despite their promise of precision medicine, these lacked Black Americans (BA) Latin (LA), who are disproportionately affected by AD. METHODS To bridge this gap, Accelerating Medicines Partnership Disease (AMP‐AD) expanded brain multi‐omics profiling to multi‐ethnic donors. RESULTS We generated data curated harmonized phenotypic from BA ( n = 306), LA 326), or 4)...
Despite advances in clinical management, cardiovascular disease remains the leading cause of death America. While cardiomyocytes retain limited plasticity following maturation, heart is grossly unable to recover from structural damage. Mesenchymal stem cell (MSC) therapy, through its promise repair and regeneration cardiac tissue, represents an exciting avenue treatment for a range diseases. MSCs are relatively immunoprivileged, lacking both major histocompatibility II T-cell co-stimulatory...
Genome engineering technologies are powerful tools in cell-based immunotherapy to optimize or fine-tune cell functionalities. However, their use for multiple gene edits poses relevant biological and technical challenges. Short hairpin RNA (shRNA)-based bypasses these criticalities represents a valid alternative CRISPR-based editing. Here, we describe microRNA (miRNA)-based multiplex shRNA platform obtained by combining highly efficient miRNA scaffolds into chimeric cluster, deliver up four...
Progressive supranuclear palsy (PSP) is a neurodegenerative parkinsonian disorder characterized by cell-type-specific tau lesions in neurons and glia. Prior work uncovered transcriptome changes human PSP brains, although their cell-specificity unknown. Further, systematic data integration experimental validation platforms to prioritize brain transcriptional perturbations as therapeutic targets are currently lacking. In this study, we combine bulk tissue (n = 408) single nucleus RNAseq 34)...
Selective potentiators of glutamate response at metabotropic receptor subtype 5 (mGluR5) have exciting potential for the development novel treatment strategies schizophrenia. A total 1,382 compounds with positive allosteric modulation (PAM) mGluR5 were identified through high-throughput screening (HTS) a diverse library 144,475 substances utilizing functional assay measuring receptor-induced intracellular release calcium. Primary hits tested concentration-dependent activity, and potency data...