Biology subjects

Cohen, C. A.

Publications and source records attributed to Cohen, C. A..

3 recordsLinked to original sources

bioRxiv2026

Natural compounds magnolol and dicoumarol enhance adipogenesis for future food applications

Edible adipose tissue can enhance the sensory and nutritional qualities of cultivated and plant-based meats, yet efficient adipogenic differentiation remains a major bottleneck and synthetic PPAR{gamma} agonists are not approved for use in food production. Here, we report a natural compound screen in 3T3-L1 adipocytes that identifies magnolol and dicoumarol as enhancers of adipogenesis; this combination also robustly promotes lipid accumulation in primary porcine dedifferentiated fat cells and ovine preadipocytes. Transcriptomic analyses show that magnolol and dicoumarol induce adipogenesis in murine and porcine cell systems through canonical adipogenic pathways with a narrower transcriptional footprint than the potent PPAR{gamma} agonist rosiglitazone. These findings support the potential of naturally occurring compounds magnolol and dicoumarol as enhancers of adipogenesis for both mechanistic studies and food-relevant applications. More broadly, our findings establish a generalizable screening framework and identify small-molecule combinations that accelerate adipose tissue engineering across murine, porcine, and ovine culture systems.

bioengineering↗

bioRxiv2024

Elucidating the Type 2 Diabetes Regulatory Network: Identification of EGFR as a Key Hub and Novel Drug Candidates

IntroductionType 2 diabetes (T2D) is a complex metabolic disorder with incompletely understood molecular mechanisms. This study aimed to elucidate the T2D regulatory network and identify potential drug targets and candidates. MethodsWe performed differential gene expression analysis on multiple T2D datasets, constructed protein-protein interaction networks, and conducted a meta-analysis to identify key hub genes. Functional enrichment analysis was performed on the resulting network. Structure-based virtual screening targeting EGFR, followed by molecular dynamics simulations, was used to identify potential drug candidates. ResultsEGFR emerged as a consistently top-ranked hub gene across studies. The regulatory network comprised hub genes, transcription factors, and miRNAs involved in processes such as apoptosis regulation, cellular response to organic substances, and reactive oxygen species metabolism. Virtual screening identified three compounds with favorable ADMET properties and strong binding affinities to EGFR, outperforming control drugs. These compounds demonstrated stable interactions in molecular dynamics simulations. ConclusionsOur integrative analysis provides new insights into the T2D regulatory network, highlighting EGFR as a potential therapeutic target. The identified drug candidates offer promising avenues for T2D treatment and related disorders involving EGFR signaling, bridging systems biology and drug discovery approaches in metabolic disease research.

bioinformatics↗

bioRxiv2021

Pan-ErbB inhibition protects from SARS-CoV-2 replication, inflammation, and injury

Targeting host factors exploited by multiple viruses could offer broad-spectrum solutions for pandemic preparedness. Seventeen candidates targeting diverse functions emerged in a screen of 4,413 compounds for SARS-CoV-2 inhibitors. We demonstrated that lapatinib and other approved inhibitors of the ErbB family receptor tyrosine kinases suppress replication of SARS-CoV-2, Venezuelan equine encephalitis virus (VEEV), and other emerging viruses with a high barrier to resistance. Lapatinib suppressed SARS-CoV-2 entry and later stages of the viral life cycle and showed synergistic effect with the direct-acting antiviral nirmatrelvir. We discovered that ErbB1, 2 and 4 bind SARS-CoV-2 S1 protein and regulate viral and ACE2 internalization, and they are required for VEEV infection. In human lung organoids, lapatinib protected from SARS-CoV-2-induced activation of ErbB-regulated pathways implicated in non-infectious lung injury, pro-inflammatory cytokine production, and epithelial barrier injury. Lapatinib suppressed VEEV replication, cytokine production and disruption of the blood-brain barrier integrity in microfluidic-based human neurovascular units, and reduced mortality in a lethal infection murine model. We validated lapatinib-mediated inhibition of ErbB activity as an important mechanism of antiviral action. These findings reveal regulation of viral replication, inflammation, and tissue injury via ErbBs and establish a proof-of-principle for a repurposed, ErbB-targeted approach to combat emerging viruses.

microbiology↗