Kendall Van Keuren‐Jensen
A5031336237- Extracellular vesicles in disease
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- RNA modifications and cancer
- Amyotrophic Lateral Sclerosis Research
- RNA regulation and disease
- Circular RNAs in diseases
- Parkinson's Disease Mechanisms and Treatments
- Molecular Biology Techniques and Applications
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurogenetic and Muscular Disorders Research
- Single-cell and spatial transcriptomics
- RNA and protein synthesis mechanisms
- Alzheimer's disease research and treatments
- Adipose Tissue and Metabolism
- Cancer Genomics and Diagnostics
- Liver Disease Diagnosis and Treatment
- Neurological diseases and metabolism
- Cell Adhesion Molecules Research
- Genetic Associations and Epidemiology
- Caveolin-1 and cellular processes
- Nanoplatforms for cancer theranostics
- CRISPR and Genetic Engineering
- Genetic Neurodegenerative Diseases
Translational Genomics Research Institute
2016-2025
National Institute of Neurological Disorders and Stroke
2024
National Institute on Aging
2024
National Institutes of Health
2024
Massachusetts General Hospital
2024
Harvard University
2024
Mayo Clinic
2023
WinnMed
2023
City of Hope
2019-2023
City Of Hope National Medical Center
2023
Highlights•Plant exosome-like nanoparticles (ELNs) are taken up by gut bacteria•The lipid composition of ELNs determines uptake specific bacteria•ELN RNAs affect bacterial genes, notably affecting Lactobacillus production I3A•ELN-mediated I3A alterations IL-22 production, resulting in ameliorated colitisSummaryThe microbiota can be altered dietary interventions to prevent and treat various diseases. However, the mechanisms which food products modulate commensals remain largely unknown. We...
The release of RNA-containing extracellular vesicles (EV) into the milieu has been demonstrated in a multitude different vitro cell systems and variety body fluids. EV are limelight for their capacity to communicate genetically encoded messages other cells, suitability as candidate biomarkers diseases, use therapeutic agents. Although EV-RNA attracted enormous interest from basic researchers, clinicians, industry, we currently have limited knowledge on which mechanisms drive regulate RNA...
To dissect therapeutic mechanisms of transplanted stem cells and develop exosome-based nanotherapeutics in treating autoimmune neurodegenerative diseases, we assessed the effect exosomes secreted from human mesenchymal (MSCs) multiple sclerosis using an experimental encephalomyelitis (EAE) mouse model. We found that intravenous administration produced by MSCs stimulated IFNγ (IFNγ-Exo) (i) reduced mean clinical score EAE mice compared to PBS control, (ii) demyelination, (iii) decreased...
The discovery and reliable detection of markers for neurodegenerative diseases have been complicated by the inaccessibility diseased tissue- such as inability to biopsy or test tissue from central nervous system directly. RNAs originating hard access tissues, neurons within brain spinal cord, potential get periphery where they can be detected non-invasively. formation extracellular release microvesicles RNA binding proteins found carry cells protect degradation. Extracellular miRNAs...
Variants of UNC13A, a critical gene for synapse function, increase the risk amyotrophic lateral sclerosis and frontotemporal dementia
Developing strategies that promote the resolution of vascular inflammation and atherosclerosis remains a major therapeutic challenge. Here, we show exosomes produced by naive bone marrow-derived macrophages (BMDM-exo) contain anti-inflammatory microRNA-99a/146b/378a are further increased in BMDM polarized with IL-4 (BMDM-IL-4-exo). These exosomal microRNAs suppress targeting NF-κB TNF-α signaling foster M2 polarization recipient macrophages. Repeated infusions BMDM-IL-4-exo into Apoe−/− mice...
Abstract Gene set enrichment analysis has become one of the most frequently used applications in molecular biology research. Originally developed for gene sets, same statistical principles are now available all omics types. In 2016, we published miRNA and annotation tool (miEAA) human precursor mature miRNAs. Here, present miEAA 2.0, supporting input from ten investigated organisms. To facilitate inclusion workflow systems, implemented an Application Programming Interface (API). Users can...
<h3>Importance</h3> Substantial genome-wide association study (GWAS) work in Parkinson disease (PD) has led to the discovery of an increasing number loci shown reliably be associated with increased risk disease. Improved understanding underlying genes and mechanisms at these will key pathogenesis PD. <h3>Objective</h3> To investigate what genomic processes underlie sporadic <h3>Design Setting</h3> This genetic used bioinformatic tools Coloc transcriptome-wide (TWAS) integrate PD case-control...
Parkinson's disease is a neurodegenerative movement disorder that currently has no disease-modifying treatment, partly owing to inefficiencies in drug target identification and validation. We use Mendelian randomization investigate over 3,000 genes encode druggable proteins predict their efficacy as targets for disease. expression protein quantitative trait loci mimic exposure medications, we examine the causal effect on risk (in two large cohorts), age at onset progression. propose 23...
Abstract Personalized medicine promises individualized disease prediction and treatment. The convergence of machine learning (ML) available multimodal data is key moving forward. We build upon previous work to deliver predictions Parkinson’s (PD) risk systematically develop a model using GenoML, an automated ML package, make improved multi-omic PD, validated in external cohort. investigated top features, constructed hypothesis-free disease-relevant networks, drug–gene interactions. performed...
Extracellular vesicles (EVs) and their cargo constitute novel biomarkers. EV subpopulations have been defined not only by abundant tetraspanins (e.g., CD9, CD63 CD81) but also specific markers derived from source cells. However, it remains a challenge to robustly isolate characterize subpopulations. Here, we combined affinity isolation with super-resolution imaging comprehensively assess human plasma. Our Single VEsicle Nanoscopy (SEVEN) assay successfully quantified the number of...
In this study, we assess 34 of the most replicated genetic associations for Alzheimer's disease (AD) using data generated on Affymetrix SNP 6.0 arrays and imputed at over 5.7 million markers from a unique cohort 1600 neuropathologically defined AD cases controls (1019 591 controls). Testing top genes AlzGene meta-analysis, confirm well-known association with APOE single nucleotide polymorphisms (SNPs), CLU, PICALM CR1 SNPs recently implicated in unusually large sets, previously CST3 ACE...
There has been a growing interest in using next-generation sequencing (NGS) to profile extracellular small RNAs from the blood and cerebrospinal fluid (CSF) of patients with neurological diseases, CNS tumors, or traumatic brain injury for biomarker discovery. Small sample volumes samples low RNA abundance create challenges downstream assays. Plasma, serum, CSF contain amounts total RNA, which make up fraction. The purpose this study was maximize isolation RNA-limited apply these methods...
Abstract Interest in circulating RNAs for monitoring and diagnosing human health has grown significantly. There are few datasets describing baseline expression levels total cell-free RNA from healthy control subjects. In this study, extracellular (exRNA) was isolated sequenced 183 plasma samples, 204 urine samples 46 saliva 55 male college athletes ages 18–25 years. Many participants provided more than one sample, allowing us to investigate variability an individual’s exRNA over time. Here...
Previous translational studies implicate plasma extracellular microRNA-30d (miR-30d) as a biomarker in left ventricular remodeling and clinical outcome heart failure (HF) patients, although precise mechanisms remain obscure.
ABSTRACT Biofluid‐accessible extracellular vesicles (EVs) may represent a new means to improve the sensitivity and specificity of detecting disease. However, current methods isolate EVs encounter challenges when they are used select specific populations. Moreover, it has been difficult comprehensively characterize heterogeneous EV populations at single vesicle level. Here, we robustly assessed from cultured cell lines via nanoparticle tracking analysis, proteomics, transcriptomics,...
Cell-free DNA (cfDNA) in urine is a promising analyte for noninvasive diagnostics. However, cfDNA highly fragmented. Whether characteristics of these fragments reflect underlying genomic architecture unknown. Here, we characterized fragmentation patterns using whole-genome sequencing. Size distribution showed multiple strong peaks between 40 and 120 base pairs (bp) with modal size 81- sharp 10-bp periodicity, suggesting transient protection from complete degradation. These properties were...
Abstract Background Parkinson’s disease (PD) is a neurodegenerative movement disorder affecting 1–5% of the general population for which neither effective cure nor early diagnostic tools are available that could tackle pathology in phase. Here we report multi-stage procedure to identify candidate genes likely involved etiopathogenesis PD. Methods The study includes discovery stage based on analysis whole exome data from 26 dominant late onset PD families, validation performed 1542...
Abstract The cellular response to stress is an important determinant of disease pathogenesis. Uncovering the molecular fingerprints distinct responses may identify novel biomarkers and key signaling pathways for different diseases. Emerging evidence shows that transfer RNA‐derived small RNAs (tDRs) play pivotal roles in responses. However, RNA modifications present on tDRs are barriers accurately quantifying using traditional sequencing. Here, AlkB‐facilitated methylation sequencing used...
The Foundational Data Initiative for Parkinson Disease (FOUNDIN-PD) is an international collaboration producing fundamental resources disease (PD). FOUNDIN-PD generated a multi-layered molecular dataset in cohort of induced pluripotent stem cell (iPSC) lines differentiated to dopaminergic (DA) neurons, major affected type PD. were derived from the Parkinson's Progression Markers study, which included participants with PD carrying monogenic variants, variants intermediate effects, and...