Exploring the therapeutic potential of cellular senescence for cardiac fibrosis

• Applicant: Kathleen Meyer, Ph.D.
• Subject Area: Cardiology, Angiology ; Pharmacology ; Cell Biology
• Term: from 2017 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 379092936

Excessive formation of extracellular matrix, a process termed fibrosis, occurs in a variety of disease pathologies and tissues, including myocardium. Although cardiac fibrosis is a hallmark of cardiovascular diseases (CVD), the major cause of death worldwide, efficient therapies are utterly needed. A novel perspective came with the finding that the cellular senescence program is involved not only in embryonic development and tumor suppression, but also in fibrogenesis (Serrano et al. 1997, Muñoz-Espín & Serrano 2014). Our previous findings showed that senescent (myo)fibroblasts restrain the development of cardiac fibrosis and identified the cellular senescence program as an antifibrotic mechanism (Meyer et al., 2016; editorial by Condorelli et al. 2016). The major aim of the proposed project is to explore the therapeutic potential of cellular senescence for cardiac fibrosis. To approach this, the different temporal dynamics of (myo)fibroblast senescence within the context of cardiac fibrosis will be analyzed. Genetically modified mouse lines will be used to trace the fate and kinetics of senescent cardiac cells. Moreover, these experiments will help to determine the efficiency of senescence-modulating drugs within cardiac diseases and validate senescence-based antifibrotic therapies in the heart in preclinical settings.

• DFG Programme: Research Fellowships
• International Connection: Spain
• Host: Professor Dr. Manuel Serrano