Biology subjects

Anbarasu, K.

Publications and source records attributed to Anbarasu, K..

5 recordsLinked to original sources

bioRxiv2026

Network-based integration of gene expression and DNA methylation identifies prognostic biomarkers for early-stage pancreatic cancer

Pancreatic ductal adenocarcinoma remains one of the most lethal malignancies, largely due to the absence of reliable early-stage biomarkers. Here, we present a network-based multi-omics framework that integrates gene expression and DNA methylation data through partial correlation analysis to uncover prognostic markers. Four distinct networks were constructed: gene expression co-expression, methylation-only, multiplex (inter-layer connections linking the same genes across omics layers), and monoplex (fused multi-omics). Weighted gene co-expression network analysis (WGCNA) was applied to each network to select non-redundant, topologically representative hub genes as features for machine learning classification. Models trained on cross-layer (multiplex) features achieved an ROC of 82%, compared with 50-60% using single-omics features alone. The most strongly associated genes with poor prognosis include TFCP2L1, DHX32, and NCK1.

cancer biology↗

bioRxiv2025

The 5-HT1A receptor antagonist WAY-100635 maleate reprograms metabolism to promote RGC differentiation and regeneration in retino-visual centers

Metabolic collapse of retinal ganglion cells (RGCs) onsets glaucoma, yet no approved drug directly protects these neurons. Through a live-cell mitochondrial screen in human stem-cell-derived hRGCs we uncovered WAY-100635 (WAY), a clinically tested 5-HT1A antagonist, as a systemic neuroprotectant. WAY triggers a reversible cyclic-AMP surge that activates PGC-1-driven reversible mitochondrial biogenesis and suppresses apoptosis. In glaucoma associated OPTNE50K hRGCs, WAY restores mitochondrial fitness, dampens excitotoxicity, and reprograms metabolism toward aerobic glycolysis, while in progenitors WAY boosts mitochondrial cristae maturation, oxidative phosphorylation, and cell-cycle exit to accelerate RGC specification. Daily intraperitoneal dosing preserves RGC bodies, neural activity, promotes axon regeneration into the optic nerve and vision centers after optic-nerve crush, as well as shows RGC protection and maintenance of visual acuity in chronic ocular hypertension glaucoma. As the non-invasive neuroprotective therapy with a human safety profile, WAY addresses a critical gap in glaucoma care and potentially for other mitochondrial optic neuropathies. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=187 SRC="FIGDIR/small/659983v1_ufig1.gif" ALT="Figure 1"> View larger version (65K): org.highwire.dtl.DTLVardef@131ff3eorg.highwire.dtl.DTLVardef@16c4e6borg.highwire.dtl.DTLVardef@190724eorg.highwire.dtl.DTLVardef@4067e4_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2024

Anti-Candida and antibiofilm activity of epinecidin-1 and its variants

To boost the stability and antimicrobial efficacy of the antimicrobial peptide (AMP) epinecidin-1, we previously engineered two variants -- variant-1 and variant-2--by substituting alanine and histidine residues with lysine. This modification led to improved structural integrity and antibacterial function. Our current study builds on this foundation by assessing the anti-Candida capabilities of epinecidin-1 and its variants against test organisms Candida albicans, Candida tropicalis, and Candida krusei. Both variants exhibited potent anti-Candida activity, particularly in disrupting biofilm formation. Minimum Inhibitory Concentrations (MICs) were found to be decreased for both variants compared to the original epinecidin-1 peptide, with variant-2 exhibiting the strongest activity. Electron microscopy confirmed that the mechanism of action involves pore formation and the induction of reactive oxygen species in the Candida cell membrane. Computational analysis showed the peptides have a high tendency to interact with the Candida cell membrane proteins like Exo-B-(1,3)-Glucanase, Secreted aspartic proteinase (Sap) 1, and N-terminal domain adhesin: Als 9-2, to prevent biofilm development.

bioengineering↗

bioRxiv2022

Enhanced mitochondrial biogenesis promotes cell survival in human stem cell derived retinal ganglion cells of the central nervous system

Mitochondrial dysfunctions are widely afflicted in central nervous system (CNS) disorders with minimal understanding on how to improve mitochondrial homeostasis to promote neuroprotection. Here we used human stem cell differentiated retinal ganglion cells (hRGCs) of the CNS, which are highly sensitive towards mitochondrial dysfunctions due to their unique structure and function, to identify mechanisms for improving mitochondrial quality control (MQC). We found that hRGCs are efficient in maintaining mitochondrial homeostasis through rapid degradation and biogenesis of mitochondria under acute damage. Using a glaucomatous Optineurin mutant (E50K) stem cell lines, we saw that at basal level mutant hRGCs possess less mitochondrial mass and suffer mitochondrial swelling due to excess ATP production load. Activation of mitochondrial biogenesis through pharmacological inhibition of the Tank binding kinase 1 (TBK1) restored energy homeostasis, mitigated mitochondrial swelling with neuroprotection against acute mitochondrial damage for glaucomatous E50K hRGCs, revealing a novel neuroprotection mechanism.

neuroscience↗

bioRxiv2021

Selection-free non-viral method revealed highly efficient CRISPR-Cas9 genome editing of human pluripotent stem cells guided by cellular autophagy

Cationic liposome-mediated delivery of drugs, DNA, or RNA plays a pivotal role in small molecule therapy, gene editing, and immunization. However, our current knowledge regarding the cellular structures that facilitate this process remains limited. Here, we used human pluripotent stem cells (hPSCs), which form compact colonies consisting of dynamically active cells at the periphery and epithelial-like cells at the core. We discovered that cells at the colony edges selectively got transfected by cationic liposomes through Arp2/3 dependent dynamic lamellipodia, which is augmented by myosin II inhibition. Conversely, cells at the core establish tight junctions at their apical surfaces, impeding liposomal access to the basal lamellipodia and thereby inhibiting transfection. In contrast, liposomes incorporating mannosylated lipids are internalized throughout the entire colony via receptor-mediated endocytosis. These findings contribute a novel mechanistic insight into enhancing therapeutic delivery via liposomes, particularly in cell types characterized by dynamic lamellipodia, such as immune cells, or those comprising the epithelial layer. Significance StatementDrug or gene delivery to human cells is essential for effective treatment. Cationic liposomes provide a safe delivery vehicle compared to viruses. However, the cellular structures required for internalizing liposomes are not yet fully understood. Using human stem cells which grow in compact colonies with more dynamic cells at the periphery and epithelial like cells at the center, here we discovered that Arp2/3 dependent dynamic lamellipodia promotes cationic liposome delivery in dynamic cells while receptor mediated endocytosis is required for epithelial cells. This is significant as it provides mechanisms for enhancing liposome delivery to both migratory and epithelial cells in our body. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/444342v2_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@800db1org.highwire.dtl.DTLVardef@1031a31org.highwire.dtl.DTLVardef@aca227org.highwire.dtl.DTLVardef@1c9df00_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO Mechanisms for liposome transfection to the lamellipodial or epithelial cells. Data shown here suggest cationic liposomes fuse with the negatively charged dynamic lamellipodia membrane in an Arp2/3 dependent manner and the process is enhanced by Myosin II inhibition, such as with the stem cell colony edge cells. However, cells more epithelial in nature such as those inside the stem cell colony center do not possess dynamic lamellipodia at the apical surface, rather they form tight junctions which inhibit cationic liposome transfection. Epithelial cells rely on receptor mediated endocytosis in both Myosin II dependent and independent manners to internalize liposomes with lipids that contain ligands for cell surface receptors such as mannose. C_FIG

cell biology↗