Biology subjects

Finke, D.

Publications and source records attributed to Finke, D..

3 recordsLinked to original sources

bioRxiv2026

HDAC inhibition via suberoylanilide hydroxamic acid (SAHA) ameliorates Doxorubicin-induced cardiotoxicity

BackgroundAnthracycline-induced cardiotoxicity remains a major limitation of cancer therapy, and effective preventive strategies are lacking. Topoisomerase II{beta} (Topo IIb) has been implicated as a central driver of this toxicity, suggesting that epigenetic regulators may interfere with pathological cardiac response. Methods and ResultsHere, we show that doxorubicin promotes Topo IIb accumulation at cardiomyocyte gene promoters (e.g., Actc1, Myl2, and Myh7) overlapping myocyte enhancer factor 2 (MEF2) binding sites and enhances MEF2-dependent transcription. This response is attenuated by the pan-histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA). SAHA-mediated cardioprotection requires class IIa HDACs, as genetic loss of HDAC4 abolishes its effect. Mechanistically, SAHA induces acetylation of the chaperone 14-3-3, disrupting its interaction with HDAC4/5, promoting their nuclear accumulation, and repressing MEF2-driven transcription. In vivo, SAHA mitigates doxorubicin-induced cardiotoxicity. ConclusionThese findings identify HDAC inhibition as a cardioprotective repurposing strategy and reveal a mechanistic link between epigenetic regulation and anthracycline-associated cardiotoxicity.

molecular biology↗

bioRxiv2025

ZEB1 Is a Key Regulator of Cardiomyocyte Structure and Function

BackgroundOur previous work identified the transcription factor "Zinc Finger E-Box Binding Homeobox 1" (ZEB1) as a downstream effector of Cytoplasmic Polyadenylation Element Binding Protein 4 (CPEB4), an RNA-binding protein responsive to cardiac stress. While ZEB1 is known for its role in cancer metastasis and epithelial-to-mesenchymal transition (EMT), its function in cardiomyocytes is not well understood. Based on previous findings, we hypothesize that ZEB1 is essential for maintaining the structural integrity and mitochondrial function of cardiomyocytes. MethodsAAV9-Zeb1 was used for the overexpression of Zeb1. Using a myosin heavy chain alpha (MHC) Cre system, we created a Zeb1 conditional knockout mouse. To evaluate cardiac function and structure, we used echocardiography, electron microscopy, immunohistochemistry. We identified differentially expressed genes following Zeb1 deletion using RNA-seq and determined direct Zeb1 target genes by integrating this transcriptome data with a Zeb1 ChIP-seq dataset. ResultsZEB1 deletion leads to sarcomere damage, mitochondrial dysfunction, and dedifferentiation, with more pronounced effects in females. Overexpression promotes hypertrophic remodeling. Echocardiographic analysis showed progressive systolic dysfunction, and histology revealed sarcomeric disarray, again especially in females. A tamoxifen-inducible ZEB1 knockout mouse model only confirmed ZEB1s crucial role in fully differentiated cardiomyocytes in female mice. Integrated analysis of RNA-seq and ChIP-seq revealed that Zeb1 directly regulated mitochondrial genes, thereby playing a critical role cardiomyocyte energy supply and having secondary effects on cardiac structure and function. ConclusionsZEB1 is critical for cardiomyocyte homeostasis, and maintaining its function is necessary for normal cardiac performance and structure.

molecular biology↗

bioRxiv2025

The Bacterial Methylorubrum extorquens Product TS201 Induces Multiple Modes of Action to Reduce Insect Feeding Damage on Maize

Microbial technologies are increasingly adopted to improve sustainable agriculture amid escalating economic, regulatory, and ecological pressures, yet few, if any, are supported by mechanistic understanding that translates to real-world performance. Here, we report TS201, a U.S. EPA-registered bioinsecticide, composed of Methylorubrum extorquens, that enhances maize yield and resilience under pest pressure. Across seven years (2016-2022) of field trials at 22 U.S. locations, TS201 increased yield and reduced lodging. Large-scale evaluations at 81 sites in eight U.S. states (2023-2024) confirmed its agronomic benefit. Mechanistically, TS201 induced biosynthesis of methyl anthranilate, a volatile insect-repellent compound, and triggered pest avoidance of treated roots. These findings reveal a novel plant-microbe-insect interaction and establish a systems biology framework for harnessing microbial plant resilience to advance crop production.

plant biology↗