Biology subjects

Chaubey, A.

Publications and source records attributed to Chaubey, A..

2 recordsLinked to original sources

bioRxiv2026

Plasma Extracellular Vesicle Lipidomics Reveals an SMPD1-Driven Sphingomyelin Salvage Pathway Collapse in Parkinson's Disease

While lysosomal lipid dysregulation is implicated in Parkinsons disease (PD), identifying the precise enzymatic drivers remains limited by the lack of subcellularly resolved metabolic mapping. Leveraging endosome-origin plasma extracellular vesicle (PsEV) lipidomics, we identified a profound bidirectional disruption of the ceramide-sphingomyelin (SM) axis in PD, driven by asymmetric upregulation of sphingomyelin phosphodiesterase 1 (SMPD1) and sphingomyelin synthase 1 (SGMS1). BODIPY-C5 SM tracking revealed that SMPD1 perturbation severely impairs lysosomal SM turnover. Crucially, this SMPD1-driven hydrolysis forces a salvage pathway collapse, bottlenecked by SPHK1/SGPL1 downregulation, which precipitates oxidative membrane damage and PINK1/Parkin-dependent mitophagy failure. We robustly validated this multi-pathway dysfunction across orthogonal in vitro, in vivo mouse, and postmortem human brain models. Furthermore, SMPD1/SGMS1 expression distinctly stratifies clinical phenotypes, marking the aggressive Postural Instability/Gait Difficulty (PIGD) subtype. Our findings establish SMPD1-mediated lysosomal impairment and ceramide-SM imbalance as a core biochemical axis in PD pathophysiology.

neuroscience↗

bioRxiv2021

Mesenchymal-like glioma cells are enriched in the gelatin methacrylate hydrogels

Glioblastoma is the most lethal primary malignant brain tumor in adults. Simplified two-dimensional (2D) cell culture and neurospheres in vitro models fail to recapitulate the complexity of the tumor microenvironment, limiting its ability to predict therapeutic response. Three-dimensional (3D) scaffold-based models have emerged as a promising alternative for addressing these concerns. One such 3D system is gelatin methacrylate (GelMA) hydrogels, which can be used for modeling the glioblastoma microenvironment. We characterized the phenotype of patient-derived glioma cells cultured in GelMA hydrogels (3D-GMH) for their tumorigenic properties using invasion and chemoresponse assays. In addition, we used integrated single-cell and spatial transcriptome analysis to compare cells cultured in 3D-GMH to cells in vivo. Finally, we assessed tumor-immune cell interactions with a macrophage infiltration assay and a cytokine array. We show that cells cultured in 3D-GMH develop a mesenchymal-like cellular phenotype found in perivascular and hypoxic regions present in the core of the tumor, and recruit macrophages by secreting cytokines in contrast to the cells grown as neurospheres that match the phenotype of cells of the infiltrative edge of the tumor.

cancer biology↗