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).

Our review on the role of CYP1B1 in cancer development is out in Cancer Treatment Reviews!

Abstract: Cancer chemoprevention is the use of synthetic, natural or biological agents to prevent or delay the development or progression of malignancies. Intriguingly, many phytochemicals with anti-inflammatory and anti-angiogenic effects, recently proposed as chemoprevention strategies, are inhibitors of Cytochrome P450 family 1B1 (CYP1B1), an enzyme overexpressed in a wide variety of tumors and associated with angiogenesis. In turn, pro-inflammatory cytokines were reported to boost CYP1B1 expression, suggesting a key role of CYP1B1 in a positive loop of inflammatory angiogenesis. Other well-known pro-tumorigenic activities of CYP1B1 rely on metabolic bioactivation of xenobiotics and steroid hormones into their carcinogenic derivatives. In contrast to initial in vitro observations, in vivo studies demonstrated a protecting role against cancer for the other CYP1 family members (CYP1A1 and CYP1A2), suggesting that the specificity of CYP1 family inhibitors should be carefully taken into account for developing potential chemoprevention strategies. Recent studies also proposed a role of CYP1B1 in multiple cell types found within the tumor microenvironment, including fibroblasts, endothelial and immune cells. Overall, our review of the current literature suggests a positive loop between inflammatory cytokines and CYP1B1, which in turn may play a key role in cancer angiogenesis, acting on both cancer cells and the tumor microenvironment. Strategies aiming at specific CYP1B1 inhibition in multiple cell types may translate into clinical chemoprevention and angioprevention approaches.

Highlights:
•CYP1B1 triggers carcinogenesis by activating exogenous and endogenous molecules to reactive species.
•Other CYP1 family members play protecting roles against tumor formation by detoxifying carcinogenic compounds.
•CYP1B1 regulates multiple cell types within the cancer microenvironment, supporting a loop of inflammatory angiogenesis.
•Several chemopreventive phytochemicals are potent and specific CYP1B1 inhibitors.
•Specific CYP1B1 inhibition may translate into clinical chemoprevention/angioprevention approaches.

Go to the full article: D’Uva G, Baci D, Albini A and Noonan DM. Cancer chemoprevention revisited: Cytochrome P450 family 1B1 as a target in the tumor and the microenvironment. Cancer Treatment Reviews, 2017

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.