What are the pro-arrhythmic mechanisms underlying inherited cardiac diseases leading to sudden cardiac death?
Can we use human pluripotent stem cells to model complex cardiac diseases and detect in vitro the phenotypic variability seen in patients?
Our laboratory focuses on the use of human pluripotent stem cells to create in vitro models of human inherited cardiac diseases, to develop drug screening platforms and to build multicellular cardiac microtissues.
How cell metabolism and redox signaling regulate angiogenesis in health and disease conditions?
Can we cure breast cancer and melanoma progression using novel metabolic-related therapeutic approaches?
Our researches aim is to investigate the function and the regulation of these mitochondria-shaping proteins. We use an integrated approach of genetics, advanced imaging, biochemistry, physiology and electron tomography to unravel the role of these proteins in cell life and death, especially by generating and analysing mouse models of conditional ablation and overexpression of mitochondria-shaping proteins.
Is metabolism involved in pancreatic carcinogenesis?
Can we target metabolism to prevent pancreatic cancer?
Pancreatic cancer is the deadliest among the most common types of human malignancies. In light of the limited effectiveness of the current therapeutic options, substantial benefits could be gained by improving our understanding of the factors that contribute to tumor onset, particularly for patients at elevated risk, with the hope of curtailing disease incidence and enhancing the opportunity to treat it early.
Impaired metabolism is a hallmark of cancer. In the lab, we study how altered metabolism contributes to cell transformation and disease initiation. We are interested in whether pharmacological or dietary interventions can impact the susceptibility to develop pancreatic cancer.
Our laboratory mainly focusses on characterizing and subsequently manipulating pathways involved in induction of senescence, as a novel therapeutic approach in treatment of PTEN-deficient prostate tumors. Prostate cancer (PCa) at advanced stage is extremely irresponsive to conventional and targeted therapies, where chemotherapy remains of palliative benefit. These tumors often harbor PTEN-loss, which results in poor prognosis and therapy-resistance. While acute loss of PTEN induces senescence response both in vitro and in vivo, termed Pten-loss induced cellular senescence (PICS), we aim to identify novel enhancers and their target genes involved in modulating PICS. Importantly, even though senescence is demonstrated to restrict tumorigenesis in vivo, prolonged accumulation of such senescent tumor cells, have been reported to have a negative impact on the tumor microenvironment thereby allowing its progression. Thus, we aim to identify small molecule inhibitors that can selectively eliminate senescent-tumor cells. Our final aim is to implement, in tandem, a ‘Pro-senescence approach’ followed by ‘Senolytic therapy’.
What is the impact of androgens on age-related diseases, such as prostate cancer and neurodegeneration?
How does the amplification of androgen receptor function alter gene expression ultimately triggering cancer and neurodegeneration?
Cancer and neurodegenerative diseases represent a major health burden for the world. Aging is the major risk factor for these untreatable diseases. We are interested in understanding i) What is the relationship between protein context (structure and function) and neurotoxicity/cancer; ii) How specific extra- and intra-cellular signaling pathways directly target the disease-related protein through post-translational modifications that suppress and enhance toxicity; iii) How single-cell molecular identity shapes selective neuronal vulnerability; and iv) What is the role of peripheral tissues in the neurodegenerative process.
What are the roles of reactive oxygen species (ROS) in the cytotoxic immunity against cancer and how can they be targeted to eradicate cancer?
The role of the immune system in the fight against cancer is undeniable. In this regard, Natural killer (NK) cells and cytotoxic T lymphocytes (CTL) are respectively innate and adaptive cytotoxic lymphocytes dedicated to kill cancer cells. In the lab, we are using a model of glioblastoma multiforme (GBM), a very lethal primary brain tumor, to investigate the cell death mechanism triggered by these cytotoxic lymphocytes and how they are regulated by microenvironmental metabolites such as reactive oxygen species (ROS) in order to design new therapeutics. To meet this goal, we use combined approaches at the intersection of biochemistry, chemistry, cell biology, proteomics, genomics and bioinformatics.
Which are the signals regulating adult skeletal muscle growth and function?
How are these signals regulated by exercise?
Adult skeletal muscle is an extremely plastic tissue, rapidly modifying its size and function responding to changes in demands. In the lab we are focusing our attention on the intracellular signaling pathways regulating increases in both mass and function of adult skeletal muscle. Considering the significant problems which arise during aging, disuse and numerous other pathologies like cancer cachexia, leading to muscle atrophy and weakness, together with the well-established beneficial effect of exercise, it is of fundamental importance to understand which pathways regulate muscle function and how these can be linked to exercise.
How the brain’s structural and functional organization mediate behaviour, both in healthy subjects, and patients with neurological disorders.
The brain remains one of the major frontiers in science. The main focus of our research is to understand how different regions in the brain interact and exchange information to mediate behavior in health and neurological disorders. We are studying the functional organization of the brain, and how this organization supports cognitive function using advanced neuroimaging methods (fMRI, DTI, EEG/MEG, PET). We are also interested in understanding how focal lesions like stroke or tumors impact the large-scale organization of brain systems, and how modulation of these alterations may improve function.
Currently we have three research projects in the lab.
First investigating the mechanisms underpinning the creation of distinct cAMP/PKA signalling events at the outer mitochondrial membrane.
Second, Identifying the molecular players through which the cAMP/PKA axis exerts its regulatory effects on mitochondrial dynamics.
Finally, investigating the role of cAMP/PKA in the balance between cell death and survival with particular focus on non-apoptotic programmed cell death.