Biology subjects

Vogt, B. J.

Publications and source records attributed to Vogt, B. J..

3 recordsLinked to original sources

bioRxiv2026

Circulating biomarkers in serum from aortic valve stenosis patients predict sex-specific drug responses in valve myofibroblasts

Aortic valve stenosis (AVS) is a prevalent, sexually dimorphic cardiovascular disease characterized by fibro-calcification of the aortic valve leaflet. Sex differences in AVS arise in part from sexually dimorphic serum composition that differentially regulate valvular interstitial cell (VIC) myofibroblast activation. However, how individual serum factors contribute to sex-specific drug responses targeting VIC myofibroblast activation remains unknown. Here, we integrate serum proteomic profiling with in vitro drug screening using hydrogel biomaterials to identify sex-specific regulators of antifibrotic drug efficacy. We found that Insulin-like Growth Factor Binding Protein 2 (IGFBP2) serum levels are associated with resistance to the antifibrotic drug Evogliptin only in female VICs cultured with female AVS serum. This mechanism is driven by IGFBP2-mediated activation of Rho/ROCK and focal adhesion kinase signaling pathways that counteract Evogliptin treatment. Our findings reveal a sex-specific, serum-mediated mechanism of Evogliptin resistance and highlight IGFBP2 as a candidate biomarker for stratifying female AVS patients for Evogliptin treatment. More broadly, these findings underscore the importance of incorporating sex-stratified biomarker analyses into AVS therapeutic development to improve patient-specific treatment recommendations.

bioengineering↗

bioRxiv2025

Ketogenesis is dispensable for the metabolic adaptations to caloric restriction

Caloric restriction (CR) extends the health and lifespan of diverse species. When fed once daily, CR-treated mice rapidly consume their food and endure a prolonged fast between meals. As fasting is associated with a rise in circulating ketone bodies, we investigated the role of ketogenesis in CR using mice with whole-body ablation of Hmgcs2, the rate-limiting enzyme producing the main ketone body {beta}-hydroxybutyrate ({beta}HB). Here, we report that Hmgcs2 is largely dispensable for many metabolic benefits of CR, including CR-driven changes in adiposity, glycemic control, liver autophagy, and energy balance. Although we observed sex-specific effects of Hmgcs2 on insulin sensitivity, fuel selection, and adipocyte gene expression, the overall physiological response to CR remained robust in mice lacking Hmgcs2. To gain insight into why the deletion of Hmgcs2 does not disrupt CR, we measured fasting {beta}HB levels as mice initiated a CR diet. Surprisingly, as mice adapt to CR, they no longer engage high levels of ketogenesis during the daily fast. Our work suggests that the metabolic benefits of long-term CR are not mediated by ketogenesis.

physiology↗

bioRxiv2024

Determining sex differences in drug combinations targeting aortic valve myofibroblast activation using an artificial intelligence derived platform

Aortic valve stenosis (AVS) is a sexually dimorphic disease where aortic valve leaflets develop fibrosis and calcification, leading to heart failure if untreated. Sex differences in AVS progression depend on valvular interstitial cells (VICs) activating to myofibroblasts that drive aberrant extracellular matrix remodeling. To date, no treatment strategies have leveraged cellular sex differences to determine drug combinations that effectively target VIC myofibroblast activation. Here, we harnessed IDentif.AI, an artificial intelligence (AI)-derived drug optimization platform, to optimize sex-specific synergistic drug combinations that may prevent and reverse VIC myofibroblast activation on hydrogel biomaterials. The results reveal that anti-fibrotic drug efficacy and combinatorial interactions are dependent on cell sex. This study provides a framework for developing clinically relevant AVS treatment strategies through the integration of high-throughput hydrogel cell culture platforms and AI-driven drug optimization. The workflow towards designing targeted AVS drug combinations may help accelerate AVS drug development for male and female patients and address health disparities in AVS treatment outcomes.

bioengineering↗