Zordoky_Lab
506 posts
@Zordoky_Lab
The overall goal of the Zordoky lab is to prevent and/or reverse the cardiovascular complications of cancer treatment
Some cancer therapies, while treating tumors, can also reveal unexpected effects on the heart! In this study, we uncover the mechanistic basis of sinus bradycardia observed in breast cancer patients treated with next-generation oral SERDs, using a powerful zebrafish preclinical model that faithfully recapitulates the clinical phenotype. We demonstrate that SERD-induced bradycardia is an on-target effect, mediated through nuclear Esr1 (ERα) signaling, rather than GPER-dependent or off-target pathways. Using Giredestrant, we show that this bradycardia is Esr1 dependent and can be effectively rescued by competitive estrogen receptor agonists. Together, these findings establish a direct mechanistic link between nuclear estrogen signaling and heart rate regulation. As SERDs move rapidly into clinical use for breast cancer therapy, understanding and mitigating cardiovascular side effects is critical. By establishing a preclinical system that mirrors patient responses, this work lays the foundation for developing strategies to preserve anticancer efficacy while reducing cardiovascular risk. I am deeply grateful to all my co-authors, my mentor @AartiAsnaniMD, and Dr. Ciara Metcalfe and her outstanding team at @genentech for their guidance, collaboration, and support throughout this work. Looking forward to continuing to contribute to translational cardiovascular science and drug discovery. #CardioOncology #HeartRate #EstrogenSignaling #PreclinicalModel #CRISPR #ZebrafishModel #JACCBTS #DrugDiscovery #CardiovascularResearch jacc.org/doi/10.1016/j.…
CD206⁺IL-4Rα⁺ macrophages proliferate and drive adverse LV remodeling via FIZZ1-mediated fibrosis. IL-4Rα deletion or silencing reverses remodeling and improves function. A novel therapeutic target in ischemic cardiomyopathy ahajournals.org/doi/full/10.11…
We are so glad to feature 2023 Oklahoma NSC Pilot Awardee Matthew Yousefzadeh in this Pilot Awardee Spotlight! Check out the full interview here: bit.ly/431MNNO
