The research program focuses on the identification of the mechanisms of action of conventional drugs and nucleic acid drugs (NABD) directed against the transcripts/proteins of disease-causing genes. Interest is also placed on the identification of delivery systems for drug targeting to cancer cells. Among the pathology of interest there are hepatocellular carcinoma and ovarian carcinoma. More recently, the selection of active molecules for the treatment of selected malignant and non-malignant skin lesions has been started. The group is also involved in the development of novel diagnostic/monitoring tests for cancer and non-cancer pathologies. With a combination of molecular, cellular, animal and bio-computer approaches, the group studies the effectiveness of the drugs, the molecular mechanisms responsible for their action and the effectiveness of novel diagnostic tools.

Progetti in corso

1) Development of active molecules for the treatment of skin lesions.

We are in the process to develop molecules that can be used in the treatment of selected malignant and non-malignant skin lesions. We will evaluate the phenotypic and molecular effects of active molecules on cell lines relevant to the skin pathologies considered. The possible toxicity of the active molecules and the ability to influence cell growth and migration will be assessed. The effects on cell growth will be analysed via cell cycle analysis by cyto-fluorimetry and direct cell count. The possible effect on cell proliferation will also be studied at the molecular level by evaluating the expression of different genes connected with the cell cycle using Western Blot and quantitative PCR. Any direct necrotic effects will be studied by lactate dehydrogenase test (LDH). The induction of apoptosis will be evaluated by studying the Caspase cascade, the poly-ADP-ribose polymerase cleavage and the annexin V test. Where possible, tests will also be performed on tissue fragments obtained from patients (ex vivo tests) and on mouse models.

2) Use of the ubiquitin-proteosome system (UPS) inhibitory drugs against ovarian adenocarcinoma

Epithelial ovarian cancer (CO) is the most lethal gynaecological cancer. Surgical removal and chemotherapy have little effect especially for the advanced forms. So, novel therapeutic strategies are needed. The use of ubiquitin-proteasome (UPS) inhibitors has given interesting results in various forms of human cancers. The aim of our project is to evaluate the therapeutic potential of a novel lead compound, 2cPE, capable of inhibiting UPS and inducing proteotoxic stress. 2cPE is an isopeptidase inhibitor, UPS component enzymes. The effects of 2cPE and its derivatives will be tested in cellular (2D and 3D models) and animal model of CO taking particular care to investigate the influence on miRNA expression.

3) Targeting of ovarian cancer cells by nanoparticles

In this project we are developing, in collaboration with Prof Cavallaro from the University of Palermo, nanoparticles containing the drug 2c. The particles will be equipped with folic acid molecules capable of interacting with folic acid receptors, over-expressed in ovarian cancer (CO) cells. The nanoparticles will also be stained by a fluorescent dye to be able to follow their fate in CO cells.

4) A novel approach based on low field nuclear magnetic resonance for the monitoring of lung condition in cystic fibrosis patients

Over the last few decades, advancements in Cystic Fibrosis (CF) management resulted in improved patient survival, with the median survival now exceeding 43 years of age. This represents a dramatic improvement compared to previous decades, as the median predicted survival was approximately 25.5 years in 1985 and 17 years in 1970.The enlarging number of long survival CF patients implicates that increased efforts are necessary to properly following these patients both from the therapeutic and from the monitoring point of view. With regard to the monitoring aspect, particularly relevant is the assessment of lung functionality since the majority of CF patients still die of respiratory failure. Lung-monitoring tests suffer from different problems including the high costs. To overcome the above limitations, we propose the use of Low-Field Nuclear Magnetic Resonance (LF-NMR) for the evaluation of the lung sputum of CF patients. LF-NMR is a non-destructive, non-invasive and low-cost approach requiring only minimal or no sample preparation. In this work we are comparing the sensibility and specificity of our novel LF-NMR based approach with those of available monitoring tools. This work is done in collaboration with the Department of Engineering of the University of Trieste and with the Burlo Garofolo Hospital.  We are also in the process to extend the use of our method to patients suffering from chronic-obstructive bronchopathy in collaboration with the director of the Pneumological Clinic of the Cattinara Hospital, Prof. M. Confalonieri. In addition, we intend to study the relationship between LF-NMR data with the rheological properties of sputum and with the infecting bacterial strains.