Biology subjects

Kober, K.

Publications and source records attributed to Kober, K..

4 recordsLinked to original sources

bioRxiv2025

Consensus Co-Expression Analysis Identifies A Common Set Of Co-Expressed Genes Associated With Diabetic Peripheral Neuropathy And Chemotherapy-Induced Peripheral Neuropathy

BackgroundDiabetic peripheral neuropathy (DPN) and chemotherapy-induced peripheral neuropathy (CIPN) are major clinical challenges with limited therapeutic options. While these conditions arise from different causes, they may share common molecular mechanisms that could be targeted for intervention. MethodsWe performed consensus weighted gene co-expression network analysis (WGCNA) on two publicly available datasets: GSE185011 (DPN vs. healthy controls in peripheral blood mononuclear cells) and GSE173610 (paclitaxel-treated vs. control iPSC-derived sensory neurons). After filtering all but the most variable genes, consensus analysis was used to identify conserved co-expression modules across both conditions. ResultsConsensus analysis identified a 193-gene module (ME3/brown) significantly associated with both DPN (correlation=0.817, p=0.0040) and CIPN (correlation=0.971, p=0.0060). Functional enrichment analysis of this module revealed pathways related to Glycolysis, FoxO signaling, Apoptosis, and Autophagy. ConclusionsOur analysis reveals a convergent molecular signature underlying both DPN and CIPN, centered on metabolic reprogramming, transcriptional stress, and programmed cell death. These findings provide a systems-level framework for developing therapies targeting shared pathological mechanisms.

systems biology↗

bioRxiv2025

Alternative Splicing And Global Transcriptome Changes Associated With LPS Stimulation In Human Peripheral Blood Mononuclear Cells

IntroductionLipopolysaccharide (LPS), a major component of gram-negative bacterial cell walls, elicits strong innate immune activation and is a widely used model for studying inflammatory responses. While the transcriptional response to LPS stimulation has been characterized, the role of alternative splicing (AS) in modulating this response remains largely unexplored. MethodsUsing deep RNA sequencing of Peripheral Blood Mononuclear Cells from three healthy female donors, we evaluated transcriptome-wide differential gene expression and alternative splicing in response to LPS stimulation. ResultsOur global differential gene expression and pathway impact analyses identified 490 differentially expressed genes and 46 significantly perturbed KEGG pathways, recapitulating known LPS-induced inflammatory responses and identifying two novel signaling pathways, (e.g., SNARE interactions in vesicular transport and the mRNA surveillance pathways). Differential alternative splicing analysis revealed critical impacts on immune-related pathways, including Toll-like receptor signaling, PI3K/AKT signaling, and pro-inflammatory macrophage polarization. Notably, we identified alternative splicing events in genes such as MyD88 and TLR4, which play key roles in terminating inflammatory signaling, as well as splicing of long non-coding RNAs (e.g., MALAT1, PVT1) with potential regulatory functions in immune responses. DiscussionThis study is the first transcriptome-wide characterization of alternative splicing in response to LPS stimulation in PBMCs. Our findings suggest that alternative splicing is a fundamental regulatory mechanism in the inflammatory response and provides potential targets for therapeutic intervention in immune-related conditions.

immunology↗

bioRxiv2023

Isolectin B4 (IB4)-conjugated streptavidin for the selective knockdown of proteins in IB4-positive (+) nociceptors

In vivo analysis of protein function in nociceptor subpopulations using antisense oligonucleotides and short interfering RNAs is limited by their non-selective cellular uptake. To address the need for selective transfection methods, we covalently linked isolectin B4 (IB4) to streptavidin and analyzed whether it could be used to study protein function in IB4(+)-nociceptors. Rats treated intrathecally with IB4-conjugated streptavidin complexed with biotinylated antisense oligonucleotides for protein kinase C epsilon (PKC{varepsilon}) mRNA were found to have: a) less PKC{varepsilon} in dorsal root ganglia (DRG), b) reduced PKC{varepsilon} expression in IB4(+) but not IB4(-) DRG neurons, and c) fewer transcripts of the PKC{varepsilon} gene in the DRG. This knockdown in PKC{varepsilon} expression in IB4(+) DRG neurons is sufficient to reverse hyperalgesic priming, a rodent model of chronic pain that is dependent on PKC{varepsilon} in IB4(+)-nociceptors. These results establish that IB4-streptavidin can be used to study protein function in a defined subpopulation of nociceptive C-fiber afferents.

neuroscience↗

bioRxiv2022

Global Endometrial DNA Multi-omics Analysis Reveals Insights into mQTL Regulation and Associated Endometriosis Disease Risk

Endometriosis is a leading cause of pain and infertility affecting millions of women globally. Identifying biologic and genetic effects on DNA methylation (DNAm) in endometrium increases understanding of mechanisms that influence gene regulation predisposing to endometriosis and offers an opportunity for novel therapeutic target discovery. Herein, we characterize variation in endometrial DNAm and its association with menstrual cycle phase, endometriosis, and genetic variants through analysis of genome-wide genotype data and methylation at 759,345 DNAm sites in endometrial samples from 984 deeply-phenotyped participants. We identify significant differences in DNAm profiles between menstrual cycle phases and at four DNAm sites between stage III/IV endometriosis and controls. We estimate that 15.4% of the variation in endometriosis is captured by DNAm, and identify DNAm networks associated with endometriosis. DNAm quantitative trait locus (mQTL) analysis identified 118,185 independent cis-mQTL including some tissue-specific effects. We find significant differences in DNAm profiles between endometriosis sub- phenotypes and a significant association between genetic regulation of methylation in endometrium and disease risk, providing functional evidence for genomic targets contributing to endometriosis risk and pathogenesis.

systems biology↗