Research topics

For years the laboratory has been studying the regulation of important metabolic pathways in pathophysiology, especially in cardiometabolic diseases in diabetes and obesity. These studies have contributed to clarify the role of nuclear receptors, co-regulators, chromatin modifiers and other factors in the transcription and epigenetic regulation of lipid, glucose and energy metabolism. At the same time, the group has consolidated its expertise in the qualitative and quantitative analysis of numerous metabolites (targeted metabolomics). The final objective is to transfer the new knowledge of metabolic regulation to clinical applications.
Main lines of research:
- Role of histone deacetylases (HDACs) and of selective inhibitors in the control of lipid, glucose and energy metabolism in the context of obesity and diabetes;
- Identification of synthetic ligands of PPARs, study of their effects on structural modifications of PPARs and characterization of their biological properties;
- Regulation of bile acid metabolism, focusing on the role of transcription factors, coregulators and chromatin modification complexes;
- Role of cholesterol, cholesterol derivatives, fatty acids and related pathways in neurodegenerative diseases;
- Identification of new mitochondrial regulators and their implication in physiology and pathophysiology;
- Study on the biological activities of natural compounds. 

Techniques

Research activities are carried out through the use of cellular and animal models. The techniques used in the laboratory are:

Genomic and transcriptomic analyses
Chromatin immunoprecipitation assays of transcription factors and epigenetic markers coupled to Next Generation Sequencing and/or quantitative PCR (qPCR)
Analysis of mutations
Gene expression by qPCR and RNA-Seq
Analysis of primary transcripts and RNA interacting proteins

Applications of liquid chromatography coupled to mass spectrometry (LC-MS/MS) for:
Identification and quantification of energy metabolites, amino acids, biogenic amines, carnitines and others by liquid chromatography tandem mass spectrometry (LC-MS/MS)
Identification and quantification of different lipid species (lipidomics)
Identification and quantification of molecules of natural origin
Peptides identification and quantification
Data analysis through bioinformatics software for the identification of regulated pathways

Biochemical and molecular biology assays
Gene cloning
Reporter systems in cell cultures
Protein-protein interaction by co-immunoprecipitation and FRET assays
Protein purification and analyses
Oxygen consumption rate in cell cultures and tissues

Animal and genetically modified models
Diabetes and obesity models
Transgenic models and knock-outs of different metabolic regulators
Assays for the evaluation of metabolic phenotypes

Collaborations

-      Various collaborations within the Department of Pharmacological Sciences
-      Prof. Gioacchino Natoli, Humanitas University, – Milano
-      Dr. Anna Maria Di Blasio, Istituto Auxologico Italiano, - Milano
-      Prof. Beatrice Desvergne, University of Lausanne, – Losanna (Svizzera)
-      Prof. Luis-Miquel Garcia Segura, Instituto Cajal – Madrid (Spagna)
-      Prof. Enrique Saez, The Scripps Reserach Institute, –La Jolla, (USA)

Selected publications

1. Audano M, Pedretti S, Cermenati G, Brioschi E, Diaferia GR, Ghisletti S, Cuomo A, Bonaldi T, Salerno F, Mora M, Grigore L, Garlaschelli K, Baragetti A, Bonacina F, Catapano AL, Norata GD, Crestani M, Caruso D, Saez E, De Fabiani E, Mitro N.
“Zc3h10 is a novel mitochondrial regulator”.
EMBO Reports.2018 Apr;19(4). pii: e45531. doi: 10.15252/embr.201745531.

2. Ferrari A, Longo R, Fiorino E, Silva R, Mitro N, Cermenati G, Gilardi F, Desvergne B, Andolfo A, Magagnotti C, Caruso D, Fabiani E, Hiebert SW, Crestani M.
“HDAC3 is a molecular brake of the metabolic switch supporting white adipose tissue browning”.
Nature Communications.2017 Jul 21;8(1):93. doi: 10.1038/s41467-017-00182-7.

3. Ferrari A, Fiorino E, Longo R, Barilla S, Mitro N, Cermenati G, Giudici M, Caruso D, Mai A, Guerrini U, De Fabiani E, Crestani M.
“Attenuation of diet-induced obesity and induction of white fat browning with a chemical inhibitor of histone deacetylases”.
International Journal of Obesity (Lond).2017 Feb;41(2):289-298. doi: 10.1038/ijo.2016.191.

4. Cermenati G, Audano M, Giatti S, Carozzi V, Porretta-Serapiglia C, Pettinato E, Ferri C, D'Antonio M, De Fabiani E, Crestani M, Scurati S, Saez E, Azcoitia I, Cavaletti G, Garcia-Segura LM, Melcangi RC, Caruso D, Mitro N.
“Lack of sterol regulatory element binding factor-1c imposes glial Fatty Acid utilization leading to peripheral neuropathy”.
Cell Metabolism.2015 Apr 7;21(4):571-83. doi: 10.1016/j.cmet.2015.02.016.

5. Muto E, Dell'Agli M, Sangiovanni E, Mitro N, Fumagalli M, Crestani M, De Fabiani E, Caruso D.
“Olive oil phenolic extract regulates interleukin-8 expression by transcriptional and posttranscriptional mechanisms in Caco-2 cells”.
Molecular Nutrition and Food Research.2015 Jun;59(6):1217-21. doi: 10.1002/mnfr.201400800