Research & Funding
We had been funded by Ministero dell’Istruzione, dell’Università e della Ricerca (Rome, Italy), in the SIR Programme (Scientific Independence of young Researchers) 2014, with a project entitled “Cross-talk between insulin signaling and oxidative stress in Alzheimer disease: a new paradigm”. The funding period is 3 years starting in July 2015.
One of the main interests of our research group is related to the role played by oxidative stress in the pathogenesis and progression of many diseases, including neurodegenerative disorders and cancer. In particular, we have focused our attention on the analysis of oxidative modifications of proteins and how dysfunction of selected proteins translate into pathological features of a disease state. By following this approach we aim to shed light on critical molecular determinants underlying aging, cognitive dysfunction and cancerogenesis process. Particularly, we focus on two main areas of research:
i) Neurodegeneration: Down Syndrome and Alzheimer Disease
We are interested in understanding how disturbance of components of the proteostasis network, that provides a critical protective role against stress conditions, may trigger neuronal death. Our results suggest that dysfunction of specific members of the protein quality control, regulating protein folding, surveillance and degradation is caused by oxidative damage. We aim to identify the specific pathways involved in the proteostasis network, which contribute to the development of Alzheimer Disease (AD) by analysing human post-mortem brain, cull culture and animal models of the disease.
Considering that Down syndrome (DS) and AD are characterized by common pathological hallmarks, we have extended our studies to identify common and divergent mechanisms of neurodegeneration by particularly focusing on mTOR signaling, insulin cascade and the crosstalk between autophagy and proteasome system. Further, we are also exploring how these pathways may represent an ideal therapeutic target to prevent neurodegenerative phenomena.
ii) Role of oxidative stress in cervical cancer
Cervical cancer is the second most common neoplastic disease among women worldwide. The initiating event is the infection with certain types of human papillomavirus (HPV), a very common condition in the general population. However, the majority of HPV infections is subclinical and transitory and is resolved spontaneously. Intriguingly, viral oncogene expression, although necessary, is not per se sufficient to promote cervical cancer and other factors are involved in the progression of infected cells to the full neoplastic phenotype. In this perspective we are interested in investigating the interplay between the viral mechanisms modulating cell homeostasis and redox sensitive mechanisms. Results obtained either from cell culture models and human tissues led us to hypothesize the mechanisms by which HPV exploits host cell survival mechanisms, through modulation of redox homeostasis. We suggest that tumor cells adapt their metabolism in order to support their growth and survival, likely creating a paradox of high ROS production in the presence of high antioxidant levels, to fit well with stress conditions.