Description

The research team is focused on the development of multiple analytical approaches for pharmaceutical analysis including:

• Identification of biomarkers and pharmaceutical targets;
• Setup and application of innovative analytical approaches for drug design and development;
• Characterization of drug-target interaction and study of metabolism of drug or xenobiotics;
• Rational design and development of bioactive molecules;
• Quality control of drugs, medical devices, food supplements, natural extracts and cosmetics;
• Isolation and characterization of natural compounds along with their in vivo and in vitro biological activity evaluation;
• Quantitative analysis of proteins, lipids and metabolites (omics studies) from animal and vegetal matrices by means of liquid chromatography-high resolution mass spectrometry;
• Bioinformatics network signaling and metabolomics studies based on omics data;

Specifically, the research team has developed a wide array of orthogonal skills concerning

1. Characterization of protein oxidation and carbonylation processes by means of proteomics and mass spectrometric approaches. The research is aimed at identifying new pharmaceutical targets and biomarkers of degenerative processes triggered by oxidation and carbonylation. The team is focused on the development of immunoistochemical and mass spectrometric methods for the identification of post translational modifications of peptide and proteins from different matrices. Such modifications are potential biomarkers for early detection of oxidative and carbonyl damage. This research line was funded by the European grant MASSTRPLAN – MASS spectrometry TRaining network for Protein Lipid adduct Analysis
2. Characterization of covalent and non-covalent drug target interactions by means of mass spectrometry. Specifically, the research is focused on the identification of ligands of proteins and nucleotides both at intact molecule level or by means of bottom-up approaches. The research includes also protein aptenation studies
3. Development of carnosine derivatives that binds cytotoxic reactive carbonyl species. Molecule design is supported by molecular modeling lab headed by Prof. Vistoli, while synthesis is supported by the labs of Prof. Dallanoce and Prof. Fumagalli. Several other international collaborations are active, including the laboratories of Prof. Anderson (University of Iowa), Dr. Fedorova (University of Dresden), Prof. Uchida (University of Tokyo), Prof. Spickett (Aston University), and Prof. Correa (Sao Paulo State University).The scope is to develop molecules able to detoxify electrophiles generated by lipid and sugar oxidation under pathological conditions, such as diabetes.
4. Analysis of natural bioactive compounds. The research includes the isolation of natural molecules, as well as their characterization, quantitation and evaluation of biological activities both in vitro and in vivo. Such activity relies on extraction techniques, spectroscopy (i.e., UV and NMR) and mass spectrometry, as well as molecular biology apparatus for the development of cell models.
5. Omics networking studies. The research is focused on studying the mode of action of molecules active as disease preventers or health maintainers. The research relies on innovative cell (2D/3D), animal and in vitro models for the characterization of protein, lipid and metabolite expression as signals of metabolic pathways modified upon treatment. Quantitative omics approaches are based on cutting edge analytical methodologies including separative techniques (i.e., nanoscale liquid chromatography, affinity chromatography, mono and bidimensional gel electrophoresis), high resolution tandem mass spectrometry, bioinformatics and statistics. This research line was funded by the European grant Marie Skłodowska-Curie Actions “MoGlyNet” (Call: H2020-MSCA-ITN-2015).
6. ADMET studies. The early evaluation of the metabolic stability of drug candidate, paralleled with the structural identification of the main metabolites is an important process in drug discovery. Metabolism information define the structural modifications needed to increase molecule stability. Simultaneously, the identification of bioactive metabolites is also important for early toxicity and efficacy assessment. The team has a long experience and several analytical skills for the analysis of drugs and metabolites in biological or vegetal matrices (e.g., plasma, skin, hepatic fractions, gastric fluids, cell culture extracts). Analytical methodologies are developed by using liquid chromatography with UV or mass spectrometry detection, both for qualitative and quantitative analyses. Besides metabolite identification the methods are used to measure cell toxicity, to analyze biological fluids from animal or human intervention studies and to study the interaction of drugs with enzyme systems, including activation/inhibition of specific targets and hepatic or non-hepatic metabolism.

ERC panels
PE4_5 Analytical chemistry
PE4_9 Method development in chemistry
PE5_11 Biological chemistry and chemical biology
PE5_18 Medicinal chemistry
LS1_13 Early translational research and drug design
LS2_8 Proteomics
LS2_9 Metabolomics
LS2_10 Glycomics/Lipidomics
LS2_11 Bioinformatics and computational biology
LS4_8 Impact of stress (including environmental stress) on physiology
LS4_9 Metabolism and metabolic disorders, including diabetes and obesity
LS4_10 The cardiovascular system and cardiovascular diseases