Biology subjects

KARMAKAR, S.

Publications and source records attributed to KARMAKAR, S..

2 recordsLinked to original sources

bioRxiv2025

Transcriptomic landscape of Gallbladder cancer reveals altered pathways related to cell cycle and Aurora kinase

BackgroundGallbladder cancer (GBC) is a rare but aggressive biliary tract malignancy. This study explores the transcriptomic profile of GBC to identify differentially expressed genes (DEGs) and dysregulated pathways involved in its pathogenesis. MethodsRNA sequencing was performed on 13 GBC tumors and 6 matched controls. Functional enrichment analysis as well as WGCNA were used to identify dysregulated pathways, functionally relevant gene modules and hub genes. Key targets were validated in patient tissues and cell lines. ResultsA total of 621 DEGs were identified (247 upregulated, 374 downregulated). Gene set enrichment analysis revealed activation of E2F targets and G2/M checkpoint, with downregulation of bile acid metabolism and estrogen response pathways. A tumor grade-correlated WGCNA module was enriched in cell cycle genes. TPX2 emerged as a central hub gene. Inhibitors of aurora kinase, TPX2 dependent enzyme, significantly reduced proliferation, migration, and invasion in GBC cells. High-grade tumors confirmed elevated Aurora kinase expression. ConclusionsThis first transcriptomic analysis of GBC in South-East Asian Indians uncovers key drivers like TPX2 and Aurora kinases in disease progression. The study highlights cell cycle dysregulation and sex-linked signatures, offering insights for biomarker discovery and targeted therapies.

cancer biology↗

bioRxiv2024

Mechanism of host cell invasion by Leishmania through KMP-11 mediated cholesterol-transport and membrane phase transition

The first step of successful infection by any intracellular pathogen relies on its ability to invade its host cell membrane. However, the detailed structural and molecular understanding underlying lipid membrane modification during pathogenic invasion remains unclear. In this study, we show that a specific Leishmania donovani (LD) protein, KMP-11, forms oligomers that bridge LD and host macrophage (M{Phi}) membranes. This KMP-11 induced interaction between LD and M{Phi} depends on the variations in cholesterol (CHOL) and ergosterol (ERG) contents in their respective membranes. These variations are crucial for the subsequent steps of invasion, including (a) the initial attachment, (b) CHOL transport from M{Phi} to LD, and (c) detachment of LD from the initial point of contact through a liquid ordered (Lo) to liquid disordered (Ld) membrane-phase transition. To validate the importance of KMP-11, we generated KMP-11 depleted LD, which failed to attach and invade host M{Phi}. Through tryptophan-scanning mutagenesis and synthesized peptides, we developed a generalized mathematical model, which demonstrates that the hydrophobic moment and the symmetry sequence code at the membrane interacting protein domain are key factors in facilitating the membrane phase transition and, consequently, the host cell infection process by Leishmania parasites.

biophysics↗