Biology subjects

Kianmehr, L.

Publications and source records attributed to Kianmehr, L..

4 recordsLinked to original sources

bioRxiv2025

Multi-Omics Integration Reveals Lipid Metabolic Reprogramming as a Driver of Cystogenesis in Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Autosomal dominant polycystic kidney disease (ADPKD) is a most common hereditary kidney disorder and a major contributor to end-stage kidney disease (ESKD), but its molecular progression mechanisms are unclear. We performed metabolomic and transcriptomic profiling on a longitudinal cohort of 254 and 47 ADPKD patients, respectively, to identify molecular alterations and then applied Multi-Omics Factor Analysis (MOFA) to uncover coordinated signatures. Disease progression was associated with a marked shift in dysregulated lipids profile, increased acylcarnitines, and increased glycolytic metabolites, suggesting a shift from fatty acid oxidation (FAO) toward glycolysis. Transcriptomic analysis revealed enrichment of PPAR signaling, cytoskeletal remodeling, and cystogenesis, providing a mechanistic link between metabolic alterations and structural dysregulation. Integrative analysis identified a central axis where inflammation, metabolic reprogramming, and cytoskeletal remodeling converges. Our integrated multi-omics analysis defines a molecular framework where transcriptomic dysregulation drives metabolic reprogramming contribute to cystogenesis, providing potential biomarkers and insights to guide precision therapy in ADPKD progression. Lay SummaryThe clinical heterogeneity of ADPKD limits current prognostic tools for early disease progression, often delaying therapeutic intervention. This study integrates longitudinal clinical data with multi-omics profiling (whole-blood transcriptomics and plasma metabolomics) in a large ADPKD cohort using Multi-Omics Factor Analysis. This approach identified coordinated molecular signatures linking aberrant gene expression and metabolic reprogramming directly to disease progression, hypertension, and mortality status. These findings uncover novel mechanistic drivers of ADPKD and suggest biomarkers to enhance early risk stratification, supporting the development of precision medicine strategies.

bioinformatics↗

bioRxiv2024

Analysis of RNA/DNA Hybrid Profiles in Blood From Autistic Patients Reveals Differences in mRNA and non-coding RNA Regions

DNA/RNA hybrids are present in normal cellular physiology, but when misregulated in the genome, they can contribute to human pathologies such as neurodevelopmental disorders and cancer. These hybrid structures are often abundant in repetitive genomic sequences such as telomeres and centromeres, contributing to evolutionary conserved phenomena. However, excessive accumulation can lead to DNA damage and genomic instability. Studies of autism spectrum disorders (ASDs) have revealed genome-wide disruptions, including mutations and significant deregulation of gene expression. Surprisingly, the common underlying factors remain unidentified. ASDs, which are of hereditary origin and more prevalent among boys, manifest themselves during development through disorders of various origins. In this study, we used whole-genome transcriptomic analysis of DNA/RNA hybrids from blood samples of autistic patients and healthy controls. we identified differences between numerous hybrid genomic regions with varying sequence compositions. Additionally, we observed local specificity in genomic regions, where RNA could either inhibit or enhance transcription. Our analysis of short RNAs hybridized with DNA revealed a striking example of transcriptional activity, where each gene is stably transcribed. We propose that non-coding RNAs originating from exons, introns or intergenic regions bind to DNA as hybrids (DNA/RNA) and influence gene expression. The specific levels of these short RNAs may regulate their own transcription, likely affecting cell fate.

molecular biology↗

bioRxiv2021

Accumulation of lncRNAs/DNA hybrid reveals RNase HII transcripts down-regulation in psoriasis.

Long functional non-coding RNAs (lncRNAs) have been in the limelight in aging research because short telomeres are associated with higher levels of TERRA (Telomeric Repeat containing RNA). The genomic instability caused in Immune-mediated inflammatory diseases (IMID) especially in patients with psoriasis, which lead to short telomeres in psoriasis lesions, is a mechanism leading to cell aging. Research on the fraction of TERRA in hybrid with DNA offers avenues for new strategies. Skin samples were fractionated to obtain the RNA associated with DNA as a R-loop structure. TERRA analysis was performed by RT-qPCR and RNA-seq analysis. The higher amount of TERRA levels attached with each chromosome end was found with psoriasis patients. The increased levels of TERRA linked with telomeres correlate with the decrease in the RNase-HII transcript which means the unresolved DNA/RNA hybrids may ultimately facilitate the formation of skin lesions. LncRNAs have multiple molecular functions, including the regulation of heterochromatin, which controls genome stability and epigenome shaping and may be used as a trans-generational prognostic marker in patients with psoriasis.

molecular biology↗

bioRxiv2020

DNA-RNA hybrid (R-loop): from a unified picture of the mammalian telomere to the genome-wide

Local three-stranded DNA-RNA hybrid regions of the genomes (R-loops) have been detected either by binding of a monoclonal antibody (DRIP assay) or by enzymatic recognition by RNaseH. Such a structure has been postulated for the mouse and human telomeres, clearly suggested by the identification of the complementary RNA TERRA. It was, however, evidenced by DRIP exclusively in human cancer and not in normal human nor in any mouse cell. Based on the observation that in several fractionation procedures, DNA-RNA hybrids copurify with double-stranded DNA, we developed a preparative approach that allows detection of stable DNA-RNA triplexes in a complex genome, their physical isolation and their RNA nucleotide sequence. We then define in the normal mouse and human genomes the notion of terminal R-loop complexes including TERRA molecules synthesized from local promoters of every chromosome. In addition to the telomeric structures since, the finding of the RNA peak, applied in addition to the whole murine sperm genomes, has highlighted a reproducible profile of the R-loop complexes from entire genome suggesting a defined profile for a future generation.

genetics↗