Tag: Gabriele D’Uva

Posted on

Glucocorticoids as a brake on cardiac regenerative factors: a novel therapeutic strategy

We are excited to announce our new publication in Nature Cardiovascular Research, in which we describe an innovative strategy to enhance heart regeneration through blockade of the glucocorticoid receptor.

In our study, we demonstrate that glucocorticoids—steroid hormones that are physiologically present in the circulation—play a key role in limiting the responsiveness of cardiomyocytes to major regenerative growth factors and cytokines. Specifically, we show that these hormones act as a true hormonal brake, contributing to the loss of the heart’s regenerative capacity during late postnatal stages and in adulthood.

A central finding of our work is the demonstration that pharmacological blockade of the glucocorticoid receptor can remove this brake, restoring the ability of cardiomyocytes to respond to proliferative stimuli. This approach substantially enhances the effectiveness of growth factor–based regenerative therapies, even in mature hearts.

In preclinical models, we further observed that the combination of a glucocorticoid receptor antagonist with a regenerative factor produces markedly superior results compared with single treatments. This effect is particularly relevant in settings of cardiac damage associated with anthracycline-based cancer therapies, where the combined approach improved cardiomyocyte survival and preserved cardiac function.

Overall, we believe that these findings open new avenues for the development of combined therapeutic strategies aimed at regenerating cardiac tissue and that, if clinically validated, they could have a significant impact on the treatment of heart failure.

Congratulations to Silvia Da Pra and Stefano Boriati, a postdoctoral researcher and a PhD student in our group, who carried out the majority of the experimental work, and thanks to all team members Carmen Miano, Francesca Sacchi, Chiara Bongiovanni, Irene Del Bono and Nicola Pianca for their contributions. We also thank the collaborators who were instrumental to the success of this project, in particular the research groups led by Eldad Tzahor (Weizmann Institute of Science, Israel), Catherine Wilson (University of Cambridge, United Kingdom), and Mattia Lauriola and Carlo Ventura (University of Bologna, Italy).

Go to the full article: : Da Pra S, Boriati S, Miano M, Sacchi F,  Batho C,  Bongiovanni C, Del Bono I, Aharonov A, Pianca N, Tassinari R, Dahir R, Ventura C, Lauriola M, Tzahor E, Wilson C & D’Uva G. Harnessing glucocorticoid receptor antagonism to enhance the efficacy of cardiac regenerative growth factors and cytokines : Nature Cardiovascular Research 2026

Read-only access to the article (no subscription required): https://rdcu.be/e2EN0

Posted on

BMP7 as a Key to Heart Regeneration: Our Progress

We are thrilled to announce our latest publication in Cell Reports! Our research indicates that a decrease in the production of growth factors, particularly BMP7, during early postnatal development contributes to the loss of regenerative capacity of the mammalian heart.
We demonstrate that BMP7 supports cardiomyocyte proliferation during the neonatal stage, and its administration boosts cardiomyocyte proliferation in postnatal life, even in adulthood, and especially after myocardial infarction. These findings suggest that BMP7 administration holds promise as a therapeutic approach for heart regeneration. Moreover, our study finds support from the zebrafish model, which naturally regenerates injured hearts. In this regard, inhibiting BMP7 impeded cardiomyocyte regeneration post-cardiac injury, while its induction accelerated the process. We believe our findings pave the way for heart regenerative therapies based on the administration of BMP7.
Congratulations to Chiara Bongiovanni for leading the project, and congratulations to the other lab team members Irene Del Bono, Carmen Miano, Stefano Boriati, Silvia Da Pra, Francesca Sacchi, Francesca Pontis, and Ilaria Petraroia for their help and support in experimental activities. We express our gratitude to collaborators who were instrumental in the success of this project, particularly the research groups led by Eldad Tzahor (Weizmann Institute of Science, Israel), Gilbert Weidinger (University of Ulm, Germany), Stephan Heermann (University of Friburg, Germany), Mattia Lauriola, and Carlo Ventura (University of Bologna, Italy).

Go to the full article: : Bongiovanni C, Bueno-Levy H, Posadas Pena D, Del Bono I, Miano C, Boriati S, Da Pra S, Sacchi F, Redaelli S, Bergen M, Romaniello D, Pontis F, Tassinari R, Kellerer L, Petraroia I, Mazzeschi M, Lauriola M, Ventura C, Heermann S, Weidinger G, Tzahor E, D’Uva G and BMP7 promotes cardiomyocyte regeneration in zebrafish and adult mice. Cell Reports 2024

Posted on

D’Uva lab receives Cariplo grant award on cancer and cardiotoxicity

We have just received very good news: we won the research grant “Cariplo – Young Researchers“.
This grant will allow us, in parallel to ongoing studies in the field of cardiac regeneration following a heart attack, to expand our research on cancer and the emerging problem of cardiotoxicity of anticancer therapies.
Cardiotoxicity, i.e. toxic effects on heart function, is responsible for a poor quality of life and reduced survival of cancer patients, regardless of the oncologic prognosis. The aim of our research is to develop innovative strategies to limit these side effects while increasing the efficacy of anti-cancer therapies targeting HER2 (a well-known oncogene also known as ERBB2) in breast cancer patients.
The project is in collaboration with the University of Bologna and Biomedical Research Foundation / University of Turin.
These funds will also give us the opportunity to recruit another researcher into my team. Soon we will post the details.
Happy 2018 to everyone!

Posted on

Symposium on heart regeneration 2017

We are organizing a “Symposium on heart regeneration: Direct stimulation of cardiogenesis as a novel strategy for treating heart failure”. The meeting will be held at our institution (Scientific and Technological Pole, IRCCS MultiMedica, Italy) on November 16th 2017. Invited speakers include our collaborators and international leaders in heart regeneration, namely Prof. E.Tzahor (Weizmann Institute, Israel), Prof. J.Bakkers (Hubrecht Institute, The Netherlands) and Prof. Gilbert Weidinger (Ulm University, Germany).

Posted on

D’Uva lab receives ERA-CVD grant award on cardiovascular disease

We are very happy to receive a research grant  “ERA-CVD Call 2016 for Transnational Research Projects on Cardiovascular Diseases” of European Union’s Horizon 2020 Framework Programme. This grant gives us the opportunity to establish our lab in Italy, in IRCCS MultiMedica (Milan)!

The project, in collaboration with Hubrecht Institute (Netherlands), Ulm University (Germany) and Weizmann Institute of Science (Israel), will investigate heart regeneration using a comparative approach between different species.

Ischemic heart disease, such as myocardial infarction, causes a massive loss of cardiomyocytes and leads to the formation of fibrotic scar tissue, resulting in impaired cardiac function and ultimately, heart failure. Recently, it has been demonstrated that myocardium is naturally regenerated in the human heart. However, the rate of replacement is too low to repair large areas of damaged myocardium. Stimulating the very low intrinsic proliferation rate of cardiomyocytes is a promising strategy for cardiac repair in patients with heart failure. To identify such repair signals, this project will use zebrafish, where cardiomyocyte regeneration occurs naturally, and mice, where it does not. Different possible reasons for the difference in the regenerative capacity of lower vertebrate versus mammals will be explored. The goal is to develop regenerative medicine strategies based on endogenous cardiomyocyte capacities.

Proudly powered by WordPress