Biology subjects

Wahiduzzaman, M.

Publications and source records attributed to Wahiduzzaman, M..

4 recordsLinked to original sources

bioRxiv2026

NgBR controls hepatic adiponectin signaling competence through KAT7-dependent chromatin regulation

Adiponectin signaling is essential for hepatic glucose homeostasis, yet the molecular basis of adiponectin receptor responsiveness remains incompletely understood. Here, we identify the Nogo-B receptor (NgBR; NUS1) as a regulator of hepatic adiponectin sensitivity. Across human, cynomolgus monkey, and mouse datasets, hepatic NgBR expression is consistently reduced in obesity-associated diabetes, indicating a conserved metabolic signature. Hepatocyte-specific NgBR deletion abolishes the metabolic effects of the adiponectin agonist AdipoRon, resulting in impaired AMPK activation, persistent gluconeogenesis, and ceramide accumulation. Mechanistically, NgBR loss suppresses KAT7 expression and reduces histone acetylation at AdipoR1 and AdipoR2 promoters, thereby limiting receptor expression. Adeno-associated virus (AAV)-mediated restoration of hepatic NgBR reinstates KAT7-dependent chromatin activation, adiponectin receptor expression, and glucose homeostasis. These findings support a hepatocellular mechanism in which NgBR maintains adiponectin receptor competence and suggest a potential therapeutic strategy for restoring adiponectin responsiveness in metabolic disease. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=115 SRC="FIGDIR/small/726643v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@117fa66org.highwire.dtl.DTLVardef@1385297org.highwire.dtl.DTLVardef@b64369org.highwire.dtl.DTLVardef@3dd55_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2024

FerroEnrich: An Interactive web tool for computing Ferroptosis index and gene enrichment.

Ferroptosis is an iron-dependent form of controlled cell death and is characterized by the formation of lipid peroxides. Understanding gene expressions associated with ferroptosis is critical for determining its function in illnesses and potential therapeutic approaches. Despite its significance, no computational model is currently available to accurately quantify the ferroptosis incident. FerroEnrich is a sophisticated web-based tool built using R Shiny application to enumerate the occurrence of ferroptosis based on the relevant gene expressions. This tool available at https://ferroenrich.shinyapps.io/ferroenrich/ processes the input gene expression file to identify genes that are resistant or prone to ferroptosis, calculates ferroptosis index value with dynamic colored heatmap and gene network plot. This manuscript describes the design, operation and usability of FerroEnrich, including examples and a discussion of its potential impact on ferroptosis research. FerroEnrich is a vital tool for researchers, allowing them to explore and analyze complicated gene expression data related to ferroptosis.

bioinformatics↗

bioRxiv2024

Targeting fatty acid synthase suppresses tumor development in NF2/CDKN2A-deficient malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is an uncommon yet deadly cancer linked to asbestos exposure. The lack of effective early diagnosis and treatment leads to reduced life expectancy among patients with MPM. This study is aimed to identify a novel molecular target inhibitor to develop more effective therapeutics for MPM. Our drug screening assay showed that the fatty acid synthase (FASN) inhibitor cerulenin demonstrates strong and selective anti-proliferative properties against NF2/CDKN2A(p16)-deficient MPM cells, surpassing the effects of cisplatin or pemetrexed. FASN protein is frequently detected in NF2/p16-deficient MPM tumor-derived tissues (15/15, 100%), but rarely in NF2/p16-intact MPM tumors (8/25, 32%). Notably, cerulenin administration successfully reduced the growth of NF2/p16-deficient MPM tumors in xenografted mice. Cerulenin inhibits mitochondrial fission by targeting dynamin-related protein 1 (DRP1) in NF2/p16-deficient cells. Moreover, the disruption of the FASN gene leads to increased ubiquitination of DRP1. These findings suggest that FASN might play a role in the tumorigenesis of MPM cells through the regulation of mitochondrial dynamics. This research offers a novel perspective on the potential development of precision medicine for MPM.

cancer biology↗

bioRxiv2019

Tandem paired nicking promotes precise genome editing with scarce interference by p53

Targeted knock-in mediated by double-stranded DNA cleavage is accompanied by unwanted insertions and deletions (indels) at on-target and off-target sites. A nick-mediated approach scarcely generates indels but exhibits reduced efficiency of targeted knock-in. Here, we demonstrate that tandem paired nicking, a method for targeted knock-in involving two Cas9 nickases that create nicks at the homologous regions of the donor DNA and the genome in the same strand, scarcely creates indels at the edited genomic loci, while permitting the efficiency of targeted knock-in largely equivalent to that of the Cas9 nuclease-based approach. Tandem paired nicking seems to accomplish targeted knock-in via DNA recombination analogous to Hollidays model, and creates intended genetic changes in the genome without introducing additional nucleotide changes such as silent mutations. Targeted knock-in through tandem paired nicking neither triggers significant p53 activation nor occurs preferentially in p53-suppressed cells. These properties of tandem paired nicking demonstrate its utility in precision genome engineering.

molecular biology↗