Translational Molecular Cardiology (Prof. Collesi)

Research Strand:

Chiara Collesi

Full professor in Biologia Molecolare (BIO11 - BIOS-08/A)

Tel: +39 040 5588747

Chiara Collesi is group leader and Associated Professor of Molecular Biology at the University of Trieste, Department of Medical, Surgical and Health Sciences. Her group aims to decipher the molecular basis of inherited cardiomyopathies through the use of Engineered Heart Tissues (EHTs) from patient-derived induced pluripotent stem cells, identified through NGS sequencing. This approach provides an advanced modeling system of the clinical, electrophysiological, and functional features of patients’ cardiac muscle and it represents a unique platform for the research and development of innovative therapies, taking advantage of the rapidly evolving delivery systems based on lipid nanoparticle technology, with a view to translational cardioprotective and pro-regenerative developments.

Her most relevant scientific contributions are:

the identification and characterization of a new tyrosine kinase receptor (Gaudino et al., 1994); the characterization of a novel post-transcriptional mechanism of tyrosine kinase receptor activation (Collesi et al., 1996); the discovery that constitutive activation of RON induces an invasive-metastatic phenotype, but not neoplastic transformation (Santoro et al., 1996).
the evidence that the Notch1 signaling stimulates the proliferation of cardiomyocytes (Collesi et al., 2008; Felician et al., 2014), the characterization of reversible acetylation as a mechanism of Notch1 signaling tuning (Collesi et al., 2018), and the identification of Notch1 signaling as indispensable for cardiovascular differentiation of immature precursors (Secco et al., 2018).
the establishment that treatment with selected microRNAs stimulates cardiac repair following myocardial infarction in pigs (Gabisonia et al., 2019), by activating regulatory pathways capable of inducing cardiomyocyte proliferation (Torrini et al., 2019).
the characterization of the molecular pathogenesis of SARS-CoV-2 infection (Braga et al., 2021; Bussani et al., 2020).
the development of an integrated translational platform (engineered cardiac tissues derived from patient-specific iPSC lines) for the study of cardiomyopathy caused by truncating variants of titin (Angriman et al., 2025; Ciucci et al., 2023; Thairi et al., 2025).

Info

Research

The Translational Molecular Cardiology group aims to decipher the molecular mechanisms underlying heart regeneration and remodelling in inherited selected cardiomyopathies, through the use of engineered heart tissues (EHTs) from patient-derived induced pluripotent stem cells, following comprehensive NGS-based genomic profiling.

The overarching objective is the establishment of an integrated validation, screening, and therapeutic development platform for innovative RNA-based interventions, employing lipid nanoparticle gene delivery, with the ultimate goal of advancing translational cardioprotective and pro-regenerative strategies.

Specific areas of focus in our lab are:

In vitro tridimensional modelling of Hereditary heart diseases
Heart regeneration
Cardiac delivery of therapeutics

In vitro tridimensional modelling of Hereditary heart diseases

Many types of heart disease are caused by a single genetic defect, but very little is often known about the molecular mechanisms underlying hereditary cardiomyopathies. To this end, we established cardiac tridimensional in vitro tissue models (EHT-Engineered Heart Tissues) derived from patient-Induced Pluripotent Stem Cells (iPSCs), to find a genotype-phenotype correlation and create a customized platform for validation, screening, and development of innovative therapies, with the aim of advancing translational, cardioprotective, and pro-regenerative therapeutic applications.

Heart regeneration

The irreversible loss of contractile tissue and the intrinsically limited regenerative capacity of the adult mammalian heart constitute primary determinants of cardiac dysfunction and the progression to heart failure. Considerable evidence suggests that the fundamental biology of the myocardium provides multiple opportunities to stimulate or boost endogenous repair mechanisms and cardiomyocyte proliferative competence. In this context, our group has previously identified and characterized fundamental molecular mechanisms governing tissue renewal and regenerative responses in the heart, thereby providing a strong conceptual and experimental framework for the development of novel therapeutic strategies for cardiovascular diseases.

Cardiac delivery of therapeutics

A crucial medical need in heart biology is the development of new drugs for myocardial infarction and heart failure, and new clinically applicable and safe gene editing protocols for inherited cardiomyopathies. Our laboratory has acquired significant expertise in gene transfer to the heart in both small (mice, rats) and large (pigs) animal models using adeno-associated virus (AAV) vectors. We are now actively engaged in the development of innovative RNA therapeutics, encompassing both coding and non-coding RNAs, for the treatment of cardiovascular disorders (CVD). Leveraging state-of-the-art instrumentation acquired through dedicated institutional funding from the University of Trieste (UniTs), we have developed proprietary formulations capable of achieving highly efficient gene transfer to heart cells both in vitro and in vivo, in view of future precision therapeutic approaches.

People

Rebecca Artioli, PhD

Maria Irshad, PhD

Michele Zanetti, PhD

Rossella Cannilla, PhD student

Sofia Fiorino, PhD student

Sofia Ciardiello, Undergraduate student

Collaboratori

Dr. Matteo Dal Ferro

Dr. Maria Perotto

Dr. Federico Angriman

Alumni

Giulia Felician, PhD (now Research Tecnician at ICGEB, Trieste).

Ilaria Secco, PhD (now Postdoctoral Research Associate at Kings’College of London, UK).

Luigi D'Ambrosio, PhD (now post-doctoral fellow at DSV, University of Trieste)

Elisa Martelletti, PhD (now Research Associate at Kings’College of London, UK).

Eleonora Capezzali, PhD (now Postdoctoral researcher at University of Udine, Italy)

Edoardo Schneider, PhD (now Project Manager Pre-Clinical Development at ForcefieldTX, London, UK)

Alice Rovai, PhD (now Postdoctoral researcher at Institut für Transfusionsmedizin und Transplantat Engineering, Hannover, Germany)

Alessia Mongelli, PhD (now Postdoctoral researcher at Center for Translational and Experimental Cardiology, Zurich, Switzerland)

Sissy Bassani, PhD (now Postdoctoral researcher at University of Zurich, Switzerland)

Marida Sansonetti, PhD (now Clinical Research Associate II, Precision for Medicine, Bethesda, MD)

Publications

Selected Publications

Collesi C., Felician G., Secco I., Gutierrez M.I., Martelletti E., Ali H., Zentilin L., Myers M., Giacca M. Reversible Notch1 acetylation tunes proliferative signaling in cardiomyocytes. Cardiovascular Research, 2018; 114:103–122.
Collesi C., Zentilin L., Sinagra G., Giacca M. Notch1 signaling stimulates proliferation of immature cardiomyocytes. J Cell Biology, 2008; 183(1):117–128.
Felician G., Collesi C., Lusic M., Martinelli V., Dal Ferro M., Zentilin L., Zacchigna S., Giacca M. Epigenetic modification at Notch responsive promoters blunts efficacy of inducing Notch pathway reactivation after myocardial infarction. Circ Res, 2014; 115(7):636–649.

High-impact journals

Braga L., Ali H., Secco I., Chiavacci E., Bussani R., Cannatà A., Collesi C. et al. Drugs that inhibit TMEM16 proteins block SARS-CoV-2 spike-induced syncytia. Nature, 2021; 594(7861):88–93.
Gabisonia K., Prosdocimo G., Aquaro G.D., Carlucci L., Zentilin L., Secco I., Collesi C. et al. MicroRNA therapy stimulates uncontrolled cardiac repair after myocardial infarction in pigs. Nature, 2019; 569(7756):418–422.
Ferguson S.M., Brasnjo G., Hayashi M., Wölfel M., Collesi C. et al. A selective activity-dependent requirement for dynamin 1 in synaptic vesicle endocytosis. Science, 2007; 316(5824):570–574.
Milosevic I., Giovedi S., Lou X., Raimondi A., Collesi C. et al. Recruitment of endophilin to clathrin-coated pit necks is required for efficient vesicle uncoating after fission. Neuron, 2011; 72(4):587–601.

High-impact clinical cardiology journals

Thairi C, Artioli R, Paulis M, Galli C, Cotič S, Paldino A, Marino I, Sinagra G, Collesi C, Dal Ferro M, Di Pasquale E. Generation of iPSC lines (ICHi001-A, ICHi002-A, ICHi003-A, ICHi004-A) from four patients carrying Titin truncating variants associated with dilated cardiomyopathy. Stem Cell Res. 2025, 86:103719.
Perotto M., Paldino A., Mazzarotto F., Collesi C. et al. Genetic and phenotypic characterization of Nexilin (NEXN) related Cardiomyopathy: results from a multicentric study. JACC Heart Fail, 2025; 13(9):102529.
Bassetto G., Merlo M., Dal Ferro M., Paldino A., Collesi C. et al. Apoptosis, a useful marker in the management of hot-phase cardiomyopathy? Eur J Heart Fail, 2024.
Bussani R., Schneider E., Zentilin L., Collesi C. et al. Persistence of viral RNA, pneumocyte syncytia and thrombosis are hallmarks of advanced COVID-19 pathology. EBioMedicine, 2020; 61:103104.

Last update: 08-06-2026 - 23:30

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