Unit of Cardio-oncology & Vascular Biology

Head of the Unit

Serena Zacchigna

The Unit’s primary objective is to investigate novel therapeutic opportunities for cardiac and aortic vascular diseases, as well as cardiac tumors.

The main research areas are:

  1. Inducing the simultaneous regeneration of cardiac muscle and new blood vessels following ischemic injury.

  2. Characterizing the cellular and molecular signatures of cardiac metastases, developing animal models of cardiac tumors, and defining the role of mechanical forces on both cardiac and tumor cells.

  3. Identifying and characterizing diagnostic and prognostic biomarkers of aortic aneurysm to support the discovery of novel pharmacological targets.

Selected Projects

  • Induction of Revascularization and Regeneration of the Ischemic Heart

    Following birth, the adult mammalian heart loses its ability to regenerate after ischemic injury. To date, strategies aimed at promoting the regeneration of new cardiac muscle and the formation of new blood vessels after myocardial infarction have largely followed parallel paths, despite the fact that both processes appear to be essential for the generation of functional cardiac tissue.

    This project aims to develop novel therapeutic approaches capable of coordinating the formation of new cardiomyocytes with the generation of new blood vessels. To achieve this goal, the research employs primary cell cultures, engineered cardiac tissues, and animal models to investigate mechanisms that can simultaneously support myocardial repair and revascularization.

    Mechanisms Controlling Tumor Cell Proliferation in the Heart

    Cardiac cells are continuously exposed to substantial mechanical stimulation resulting from both the contractile activity of the heart and the pressure and volume loads within the cardiac chambers. Mechanical stimulation increases significantly after birth in the mammalian heart, paralleling the loss of the heart’s regenerative capacity.

    This project aims to define the effects of the mechanical forces present in the adult beating heart on cardiac cell proliferation and to explore the hypothesis that these same forces may similarly inhibit tumor cell proliferation, thereby protecting the heart from cancer development.

    In addition, the project investigates alternative or complementary mechanisms that may influence the growth of tumor cells within the myocardium, including the role of immune system cells and their interactions with the cardiac microenvironment.

    Aortic Aneurysms

    Aortic aneurysms are common in populations of industrialized countries, and their incidence increases with age. These conditions are associated with high rates of morbidity and mortality, yet effective pharmacological treatments are still lacking.

    Currently, surgical replacement of the dilated segment of the aorta remains the only definitive treatment for aortic aneurysms, as the pharmacological strategies available to date have shown only limited effectiveness in preventing the progression of aortic dilation. Because aortic aneurysms are often undiagnosed and can lead to life-threatening complications, regular clinical monitoring is essential for risk management and prevention.

    However, current clinical guidelines do not provide sufficiently precise tools for predicting and reducing the risk of aortic dissection in monitored patients. Existing information on the progression of aortic dilation is largely based on changes in aortic dimensions and does not adequately account for the contribution of cellular and extracellular biomarkers.

    The objective of this research is to provide a comprehensive understanding of the molecular mechanisms underlying aneurysm formation, with the ultimate goal of identifying novel therapeutic targets and developing innovative prognostic and therapeutic strategies for patients with dilative aortic diseases.

best publications in the last three years

    • Paillard M, Abdellatif M, Andreadou I, Bär C, Bertrand L, Brundel BJJM, Chiva-Blanch G, Davidson SM, Dawson D, Di Lisa F, Evans P, Giricz Z, Hausenloy DJ, Kleinbongard P, Lezoualc'h F, Liehn E, Maack C, Maguy A, Murphy E, Perrino C, Pesce M, Rainer PP, Streckfuss-Bömeke K, Thielmann M, Tian R, Tocchetti CG, Van Der Velden J, Van Linthout S, Zacchigna S, Krieg T. Mitochondrial targets in ischaemic heart disease and heart failure, and their potential for a more efficient clinical translation. A scientific statement of the ESC Working Group on Cellular Biology of the Heart and the ESC Working Group on Myocardial Function. Eur J Heart Fail. 2025 May 4.
    • Spazzapan M, Pegoraro S, Vuerich R, Zito G, Balduit A, Longo E, Pascolo L, Toffoli M, Meshini G, Mangogna A, Ros G, Buonomo F, Romano F, Lombardelli L, Papa G, Piccinni MP, Zacchigna S, Agostinis C, Bulla R, Ricci G. Endothelial cell supplementation promotes xenograft revascularization during short-term ovarian tissue transplantation. Bioact Mater. 2025 Apr 16;50:305-321.
    • Secco I, Backovic A, Tomczyk M, Mura A, Li G, Bortolotti F, Vodret S, Dal Ferro M, Chiavacci E, Zentilin L, Sinagra G, Zacchigna S, Mano M, Giacca M. Genetic tracing and topography of spontaneous and stimulated cardiac regeneration in mice. Nat Cardiovasc Res. 2025 Apr;4(4):397-411.
    • Rodor J, Klimi E, Brown SD, Krilis G, Braga L, Ring NAR, Ballantyne MD, Kesidou D, Nguyen Dinh Cat A, Miscianinov V, Vacante F, Miteva K, Bennett M, Beqqali A, Giacca M, Zacchigna S, Baker AH. Functional screening identifies miRNAs with a novel function inhibiting vascular smooth muscle cell proliferation. Mol Ther. 2025 Feb 5;33(2):615-630.
    • Volf N, Vuerich R, Colliva A, Volpe MC, Marengon M, Zentilin L, Giacca M, Ring NAR, Vodret S, Braga L, Zacchigna S. Endothelial-to-mesenchymal transition enhances permissiveness to AAV vectors in cardiac endothelial cells. Mol Ther. 2024 Nov 6;32(11):3808-3814.
    • Myasoedova VA, Rega S, Valerio V, Moschetta D, Massaiu I, Bonalumi G, Esposito G, Rusconi V, Bertolini F, Perrucci GL, Poggio P. Exploiting the anti-fibrotic effects of statins on thoracic aortic aneurysm progression: results from a meta-analysis and experimental data. Front Pharmacol. 2024 Aug 1;15:1426982.
    • Falcão-Pires I, Ferreira AF, Trindade F, Bertrand L, Ciccarelli M, Visco V, Dawson D, Hamdani N, Van Laake LW, Lezoualc'h F, Linke WA, Lunde IG, Rainer PP, Abdellatif M, Van der Velden J, Cosentino N, Paldino A, Pompilio G, Zacchigna S, Heymans S, Thum T, Tocchetti CG. Mechanisms of myocardial reverse remodelling and its clinical significance: A scientific statement of the ESC Working Group on Myocardial Function. Eur J Heart Fail. 2024 Jul;26(7):1454-1479.
    • Gioia U, Tavella S, Martínez-Orellana P, Cicio G, Colliva A, Ceccon M, Cabrini M, Henriques AC, Fumagalli V, Paldino A, Presot E, Rajasekharan S, Iacomino N, Pisati F, Matti V, Sepe S, Conte MI, Barozzi S, Lavagnino Z, Carletti T, Volpe MC, Cavalcante P, Iannacone M, Rampazzo C, Bussani R, Tripodo C, Zacchigna S, Marcello A, d'Adda di Fagagna F. SARS-CoV-2 infection induces DNA damage, through CHK1 degradation and impaired 53BP1 recruitment, and cellular senescence. Nat Cell Biol. 2023 Apr;25(4):550-564.
    • Vuerich R, Groppa E, Vodret S, Ring NAR, Stocco C, Bossi F, Agostinis C, Cauteruccio M, Colliva A, Ramadan M, Simoncello F, Benvenuti F, Agnelli A, Dore F, Mazzarol F, Moretti M, Paulitti A, Palmisano S, De Manzini N, Chiesa M, Casaburo M, Raucci A, Lorizio D, Pompilio G, Bulla R, Papa G, Zacchigna S. Ischemic wound revascularization by the stromal vascular fraction relies on host-donor hybrid vessels. NPJ Regen Med. 2023 Feb 11;8(1):8.
    • Rega S, Farina F, Bouhuis S, de Donato S, Chiesa M, Poggio P, Cavallotti L, Bonalumi G, Giambuzzi I, Pompilio G, Perrucci GL. Multi-omics in thoracic aortic aneurysm: the complex road to the simplification. Cell Biosci. 2023 Jul 20;13(1):131.

Staff

  • Gianluca Lorenzo Perrucci, Ph.D

    Daniela Lorizio, Ph.D

    Sara Rega, M.Sc.

    Gaia Salina, M.Sc.

    Maximiliano Dalmaroni, Ph.D.