A5112116111- Bioinformatics and Genomic Networks
- CRISPR and Genetic Engineering
- Alzheimer's disease research and treatments
- Molecular Biology Techniques and Applications
- Cancer Genomics and Diagnostics
- Mitochondrial Function and Pathology
- Dementia and Cognitive Impairment Research
- Vibrio bacteria research studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Genetic Associations and Epidemiology
- RNA Research and Splicing
- Single-cell and spatial transcriptomics
- Photoreceptor and optogenetics research
- Pluripotent Stem Cells Research
- Health, Environment, Cognitive Aging
- Signaling Pathways in Disease
- Pregnancy and preeclampsia studies
- Antibiotic Resistance in Bacteria
- Metabolomics and Mass Spectrometry Studies
- Epigenetics and DNA Methylation
- Microbial Metabolism and Applications
- RNA modifications and cancer
- Metabolism and Genetic Disorders
- Tryptophan and brain disorders
- Planarian Biology and Electrostimulation
Rush University Medical Center
2018-2025
Georgia State University
2025
Rush University
2020-2024
Capital Medical University
2024
Chinese Academy of Sciences
2011-2024
Chengdu Institute of Biology
2024
Nanjing Agricultural University
2024
Northwest A&F University
2007-2023
Columbia University
2023
Institute on Aging
2023
Identifying the molecular systems and proteins that modify progression of Alzheimer's disease related dementias (ADRD) is central to drug target selection. However, discordance between mRNA protein abundance, scarcity proteomic data, has limited our ability advance candidate targets are mainly based on gene expression. Therefore, by using a deep neural network predicts abundance from expression, here we attempt track early drivers ADRD. Specifically, applying clei2block learning model 1192...
Lifetime risk of Alzheimer disease (AD) dementia is twofold higher in women compared with men, and low estrogen levels postmenopause have been suggested as a possible contributor. We examined 3 ER (GPER1, ER2, ER1) variants association AD traits an indirect method to test the between women. Although study focus was on women, comparison, we separately molecular men.Participants were followed for average 10 years one 2 longitudinal clinical pathologic studies aging. Global cognition assessed...
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,...
Abstract The biological mechanisms underlying women’s increased Alzheimer’s disease (AD) prevalence remain undefined. Previous case/control studies have identified sex-biased molecular pathways, but sex-specific relationships between gene expression and AD endophenotypes, particularly sex chromosomes, are underexplored. With bulk transcriptomic data across 3 brain regions from 767 decedents, we investigated associations post-mortem β-amyloid tau as well antemortem longitudinal cognition. Of...
5-hydroxymethylcytosine, also known as the sixth DNA base of genome, plays an important role in brain aging and neurological disorders such Alzheimer's disease. However, little is about its genome-wide distribution association with disease pathology. Here, we report a profiling 5-hydroxymethylcytosine 1079 autopsied brains (dorsolateral prefrontal cortex) older individuals assess multiple measures pathologies, including pathological diagnosis disease, amyloid-β load, PHFtau tangle density....
Abstract Mitochondrial iron overload in acquired idiopathic sideroblastic anemia (AISA) may be attributable to mutations of mitochondrial DNA (mtDNA), because these can cause respiratory chain dysfunction, thereby impairing reduction ferric (Fe3+) ferrous (Fe2+). The reduced form is essential the last step heme biosynthesis. It not yet understood which part linked. In two patients with AISA we identified point mtDNA affecting same transmembrane helix within subunit I cytochrome c oxidase...
The bioluminescent bacterium Vibrio fischeri initiates a specific, persistent symbiosis in the light organ of squid Euprymna scolopes. During early stages colonization, V. is exposed to host-derived nitric oxide (NO). Although NO can be both an antimicrobial component innate immunity and key signaling molecule eukaryotes, potential roles beneficial host-microbe associations have not been described. hnoX encodes heme NO/oxygen-binding (H-NOX) protein, member family bacterial NO- and/or...
The contribution of the different waves and sites developmental hematopoiesis to fetal adult blood production remains unclear. Here, we identify lymphatic vessel endothelial hyaluronan receptor-1 (LYVE1) as a marker yolk sac (YS) endothelium definitive hematopoietic stem progenitor cells (HSPCs). Endothelium in mid-gestation YS vitelline vessels, but not dorsal aorta placenta, were labeled by Lyve1-Cre. Most HSPCs erythro-myeloid progenitors Lyve1-Cre lineage traced, primitive erythroid not,...
Alzheimer's disease (AD) has been associated with cardiovascular and cerebrovascular risk factors (CVRFs) during middle age later is frequently accompanied by pathology at death. An interaction between CVRFs genetic variants might explain the pathogenesis. Genome-wide, gene CVRF analyses for AD, in 6568 patients 8101 controls identified FMNL2 (p = 6.6 × 10
Abstract The relationship between genetic variation and gene expression in individual brain cell types subtypes has remained elusive. Here, we generated single-nucleus RNA sequencing data from the dorsolateral prefrontal cortex of 424 individuals advanced age; analyzing 1.5 million nuclear transcriptomes, assessed effect variants on cis ( -eQTL) for 7 81 subtypes. This effort identified 10,004 eGenes at type level 8,138 subtype level. Many are only detected within A new variant influences...
Abstract Emerging evidence shows that the meninges conduct essential immune surveillance and defense at brain border, dysfunction of meningeal immunity contributes to aging neurodegeneration. However, no study exists on molecular properties cell types within human leptomeninges. Here, we provide single nuclei profiling dissected postmortem leptomeninges from aged individuals. We detect diverse types, including unique endothelial, mural, fibroblast subtypes. For cells, show most T cells...
Abstract INTRODUCTION The ɛ4 allele of the apolipoprotein E gene ( APOE ɛ4) is strongest genetic risk factor for Alzheimer's disease (AD), but mechanisms connecting to AD are not clear. METHODS Participants n = 596) were from two clinical‐pathological studies. Tissues dorsolateral prefrontal cortex examined identify 8425 proteins. Post mortem pathological assessment used immunohistochemistry obtain amyloid beta (Aβ) load and tau tangle density. RESULTS In separate models, was associated with...
Nitric oxide (NO) is implicated in a wide range of biological processes, including innate immunity against pathogens, signal transduction and protection oxidative stress. However, its possible roles beneficial host-microbe associations are less well recognized. During the early stages squid-vibrio symbiosis, bacterial symbiont Vibrio fischeri encounters host-derived NO, which has been hypothesized to serve as specificity determinant. We demonstrate here that flavohaemoglobin, Hmp, V....
Abstract INTRODUCTION The secreted phosphoprotein 1 ( SPP1 ) gene expressed by CD11c + cells is known to be associated with microglia activation and neuroinflammatory diseases. As most studies rely on mouse models, we investigated these genes proteins in the cortical brain tissue of older adults their role Alzheimer's disease (AD) related disorders. METHODS We leveraged protein measurements, single‐nuclei, RNASeq data from Religious Orders Study Rush Memory Aging Project (ROSMAP) over 1200...
Molecular subtyping of brain tissue provides insights into the heterogeneity common neurodegenerative conditions, such as Alzheimer's disease. However, existing studies have mostly focused on single data modalities and only those individuals with severe cognitive impairment. To address these gaps, we applied similarity network fusion, a method capable integrating multiple high-dimensional multi-omic simultaneously, to an elderly sample spanning full spectrum ageing trajectories. We analyzed...
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)...
Abstract Approximately 40% of dementia cases could be prevented or delayed by modifiable risk factors related to lifestyle and environment. These factors, such as depression vascular disease, do not affect all individuals in the same way, likely due inter-individual differences genetics. However, precise nature how genetic profiles interact with brain health is poorly understood. Here we combine multiple data resources, including genotyping postmortem gene expression, map landscape structure...
Abstract INTRODUCTION Dietary patterns are associated with dementia risk, but the underlying molecular mechanisms largely unknown. METHODS We used RNA sequencing data from post mortem prefrontal cortex tissue and annual cognitive evaluations 1204 participants in Religious Orders Study Memory Aging Project. identified a transcriptomic profile correlated MIND diet (Mediterranean‐Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay) among 482 individuals who...
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)...