CNC.IBILI

Metab2 | Main Goals

Our research group intends to pursue competitive research lines. Research which is of low impact and which is likely not to result in funding will be reduced and/or terminated. We will focus in the role of mitochondrial metabolism and signaling in diseases that are widespread in the world today, including obesity, cancer and metabolism and in aging-related mitochondrial metabolic alterations, since this is a hot topic for funding for the Horizon 2020 program. Within this thematic, we will strengthen research on menopause pathophysiology, since this is a prevalent condition which affects around 50% of all mankind during aging. In this context, we will focus on estrogen removal effects on cardiovascular and bone cell metabolic and mitochondrial function and whether phytoestrogens are safer alternatives to estradiol-based hormone replacement therapy. Other important research lines that will be explored in the next 5-7 years include the following:
a) Epigenetic regulation of metabolic capacity: We will investigate whether metabolic capacity in different tissues can be programmed in utero (either by diet, exercise or exposure to xenobiotics), and transmitted transgenerationally, resulting in pre-disposition to disease or accelerated aging in the adult. In the same context, we are interested in understanding how nuclear miRNAs translocated to mitochondria regulate mitochondrial gene expression and impact the development of metabolic diseases.

b) Anti-cancer toxicology. We will evaluate antiestrogens metabolites effects in combination with vitamin A derivatives on melanoma cells proliferation and migration, as well as the role of GPR30 in the antiproliferative activity of antiestrogens in melanoma and breast cancer, as well as determine hematological parameters, genotoxic effects and circulating biomarkers in humans after anticancer combined therapies.

c) Metabolic remodeling and cell differentiation. This involves understanding the metabolic remodeling occurring during cancer stem cell (CSC) differentiation. By activating or over-expressing specific mitochondrial proteins, we will manage to stimulate mitochondrial activity in CSC, leading to cell differentiation and to a more effective targeting by chemotherapeutics. In a similar context, we will investigate the therapeutic impact of the stimulation of mitochondrial metabolism during hepatic regeneration and transdifferentiation.

d) Aging and mitochondrial quality control. We are interested in investigating age-related impairment of mitochondrial homeostasis as the consequence of accumulation of defective mitochondria due to disturbance of sestrin-2, loss of macromolecular supercomplexes, oxidative stress and disrupted mitophagy. These alterations are likely to contribute to the loss of mitochondrial capacity in the different tissues due to aging.

In terms of internationalization, our future objective is to maintain our current internal, national and international collaborations, in order to foment high-impact publications, exchange of students and joint submissions to research grants. Our critical objectives also involve obtaining consistent funding, not only from the Foundation for Science and Technology, but also from international funding agencies. Although being very competitive, we will use the excellence of our research to obtain mode international funding. This is also obtained by trying to increase even more the impact factor of our publications, trying to have at least 2 publications in peer-reviewed journals with IF>8 every year. In order to have a competitive group, it is imperative that we maintain a constant body of 1-2 laboratory managers/laboratory technicians, which can be hired for a period of 5 years in order to help new students and collaborate in the general organization of the group.