Projects

The Systems Medicine laboratory makes use of experimental and computational approaches to molecularly characterise pathological and physiological processes. In particular, we analyse large biomolecular and clinical datasets with machine learning methods to formulate hypotheses, and validate results experimentally using biochemistry, molecular biology, and cellular and in vivo experiments.

The main objectives of the laboratory are:

to identify new functions of cholesterol synthesis intermediates in cancer, development and homeostasis;
to identify novel molecular targets in heart failure;
to molecularly characterise genetic factors that predispose to diabetes;
to characterise new molecules that promote longevity.

Open positions

There are open positions for talented researchers interested in metabolism. If you would like to be part of the team, send Elisa your CV and a cover letter with your application to join the laboratory.

Cholesterol Biosynthesis Intermediates

We are generously funded by the Human Technopole Early Career Fellowship to study the biological functions of distal cholesterol biosynthesis intermediates.

Choleterol Biosynthesis Intermadiates (CBIs) are largely unexplored despite their potential importance and existing evidence suggests they have unique signaling properties.

We have previously shown that some CBIs (lanosterol, desmosterol) can modulate cellular function and genetic variation in CBI genes is associated with traits beyond cholesterol levels.

The aim of this project, fully funded by the Human Technopole Early Career Fellowship, is to:

Identify proteins that interact with CBIs and mediate their signaling.
Discover gene regulatory networks influenced by CBIs using computational approaches.
Investigate the role of CBIs in relevant pathologies.

To this aims, we will combine experimental (cell-based assays, in vivo models) and computational approaches (machine learning, biobank data analysis), and validate the findings with in vivo experiments and clinical samples.

This research could significantly impact our understanding of cholesterol metabolism and its role in health and disease, and there is potential for developing new therapeutic targets and interventions based on CBI manipulation.
In essence, we aim to move beyond the traditional view of CBIs as mere precursors to cholesterol and explore their unique biological functions as signaling molecules.

Amidated hormones and GLP-1 signaling in diabetes

We are generously funded by the European Research Council (ERC Starting Grant) to study the role of amidated hormones in GLP-1 and GLP-1 receptor agonist signaling in diabetes.

A significant subset of patients with type 2 diabetes mellitus experience limited or no response to GLP-1RAs. We have shown that endogenous amidated hormones play a crucial role in modulating GLP-1 secretion and function, influencing GLP-1RA effectiveness.

This research aims to:

Investigate the impact of amidated hormone deficiency on GLP-1 secretion and function in vitro and in vivo.
Use genetically engineered mice to dissect the contribution of specific amidated hormones to GLP-1RA resistance.
Leverage machine learning to analyze clinical data and identify patient characteristics that predict GLP-1RA response.
Explore therapeutic approaches to prevent or overcome GLP-1RA resistance.

Our final goal is to unravel the intricate mechanisms driving GLP-1RA resistance in T2DM, paving the way for more effective and personalized treatment approaches.

Big Data Analysis for Biomedicine

Works in progress...

Stay tuned for updates!