Stanford Advisors

Contact

  • Academic
    mkay3@stanford.edu
    University - Scholar Department: Cardiothoracic Surgery Position: Postdoctoral Scholar

Additional Info

  • Mail Code: 5407

All Publications

  • Enhancing cardiac serine biosynthesis mitigates the progression of dilated cardiomyopathy. Metabolism: clinical and experimental Kay, M., Samuelsson, A. M., Bharucha, N., Li, X., Ramchandani, R., Baum, R. E., Ruiz, D., Laguerre, A., Lajevardi, S., Kambhampati, S., Metallo, C. M., Kapiloff, M. S., Karakikes, I. 2025: 156395

    Abstract

    Genetic dilated cardiomyopathy (DCM) is a leading cause of heart failure. However, disease-modifying therapies remain limited. Metabolic dysfunction has emerged as a key driver of DCM pathogenesis, and impaired serine biosynthesis, catalyzed by the rate-limiting enzyme phosphoglycerate dehydrogenase (PHGDH), has recently been identified as a potential therapeutic target. Here, we evaluated the therapeutic potential of increasing serine biosynthesis through AAV9-mediated PHGDH gene augmentation in a transgenic TM54 mouse model of DCM with established pathology. Longitudinal echocardiography showed preserved systolic function and prevented ventricular dilatation in TM54 mice treated with AAV9-PHGDH compared to AAV9-GFP controls. Histological analysis revealed reduced myocardial fibrosis and cardiomyocyte hypertrophy in AAV9-PHGDH-treated TM54 hearts, indicating a reversal of pathological remodeling. Metabolic profiling, including targeted metabolomics and in vivo 13C-glucose tracing analysis, revealed that serine levels increased in hearts treated with AAV9-PHGDH, accompanied by decreases in glucose-derived pyruvate and lactate. At the same time, mitochondrial oxidative metabolism remained intact, indicating a shift of glycolytic carbon towards serine biosynthesis. Collectively, these findings show that enhancing cardiac serine synthesis through PHGDH gene augmentation therapy preserves contractile function and mitigates disease progression in vivo, suggesting a novel metabolic therapeutic strategy for DCM.

    View details for DOI 10.1016/j.metabol.2025.156395

    View details for PubMedID 40975489

  • Development of a Novel AAV Gene Therapy for the Treatment of Dilated Cardiomyopathy Chiola, S., Sen, D., Kay, M., Xu, J., Champe, M., Urbinati, F., Karakikes, I. CELL PRESS. 2025

    View details for Web of Science ID 001521594200212