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Ministerul Cercetării, Inovării şi Digitalizării, Unitatea Executivă pentru Finanțarea Învățământului Superior, a Cercetării, Dezvoltării și Inovării (UEFISCDI)

Funding authority: Ministry of Research, Innovation and Digitization, Executive Agency for Higher Education, Research, Development and Innovation (UEFISCDI)

Project duration: 01/07/2025 - 30/06/2028

Director de proiect/Project director: Adrian Manea, Ph.D., Institute of Cellular Biology and Pathology "N. Simionescu", Bucharest, Romania (e-mail: adrian.manea@icbp.ro)

Membrii echipei proiectului/Team members:

1.      Adrian Manea, PhD (Project director)
2.      Acad. Maya Simionescu
3.      Horia Muresian, MD, PhD
4.      Simona-Adriana Manea, PhD
5.      Mihaela-Loredana Vlad, PhD
6.      Alexandra-Gela Lazar, PhD
7.      Gabriela Dumitrescu, PhD Student

Project summary:

Atherosclerosis-related cardiovascular diseases represent the main cause of morbidity and mortality, and impose among the highest socio-economic costs worldwide. Epitranscriptomic modifications play major roles in regulating the flux of genetic information by controlling the mRNA splicing, nuclear export, translation and decay. Although clinical important, the functional implication of epitranscriptomic mechanisms in atherogenesis remains largely unknown. We hypothesize that the dysregulation of specific epitranscriptomic mechanisms and the ensuing adverse RNA methylation signatures significantly contribute to gene and protein expression alterations that are functionally and coordinately implicated in the pathoetiology of atherosclerosis. The scope of this project is to identify m⁶A RNA imprints characteristically associated with atherosclerotic disease and functionally characterize selected m⁶A RNA-modifying enzymes/binding proteins regulating mRNA transcripts specifying for key molecular effectors mechanistically linked to atherosclerosis. The proposed strategy entails experiments on human biological samples, in vitro/in vivo models of atherosclerosis, and state-of-the-art techniques. Expected outcomes: (1) Novel mechanistic insights into the role of dysregulated epitranscriptomic mechanisms in atherogenesis. (2) Understanding the broad outcomes of selected m⁶A RNA-oriented pharmacological interventions in atherosclerosis in view of further clinical development and testing.