Liver-Brain Unit “Rita Moretti”

Name of the Group:

Liver-Brain Unit “Rita Moretti”

 Silvia Gazzin (Senior Scientist)
 John Paul Llido (PhD Student)
 Camilla Dalla Verde (PhD Student)

 Cristina Bellarosa (Senior Scientist)
 Benedetta Blarasin (PhD Student)
 Eva Dariol ( Master Degree Student)

The group is active in several fundamental research areas, including severe neonatal jaundice (kernicterus), Parkinson's disease, and the development of new tools for studying liver pathologies.

In the context of kernicterus, we are currently investigating: A) The epigenetic impact of bilirubin on brain development, which has transient effects (e.g., on differentiation, synaptogenesis, plasticity, repair, energy metabolism, etc.) localized to specific brain structures, with a trascriptomic imprinting in motor areas. The identified genes may explain the higher frequency of neuropsychiatric syndromes in adulthood for individuals who experienced neonatal jaundice. B) We are also investigating genetic variables that may be responsible for the symptomatic variability observed in clinical cases, with the ultimate goal of creating a diagnostic chip that allows for more precise identification of neonates at risk of neurological damage, optimizing and individualizing treatments. C) Based on the acquired biomolecular knowledge, we are validating pharmacological approaches (primarily curcumin) to counteract neurological damage despite the presence of severe jaundice. These approaches are easily applicable even in low-income countries where neonatal jaundice still causes neonatal death.

A parallel project concerns the role of calcium homeostasis in bilirubin-induced neurotoxicity, aiming to find new therapeutic approaches to prevent permanent neurological damage in neonates affected by severe and prolonged hyperbilirubinemia.

A parallel project concerns the role of calcium homeostasis in bilirubin-induced neurotoxicity, aiming to find new therapeutic approaches to prevent permanent neurological damage in neonates affected by severe and prolonged hyperbilirubinemia. In the field of neurodegenerative diseases, following the identification of the beneficial effect of low doses of bilirubin on the death of dopaminergic neurons caused by TNF-alpha, two directions of research are being pursued: In collaboration with the University of Turin, the validation of a nano delivery system of bilirubin (nanobubbles) to the substantia nigra is underway. An alternative in vitro model of slow degeneration of dopaminergic neurons in Parkinson's disease is also being developed. This model will be used as a platform for screening compounds with anti-inflammatory action. Compounds will be selected through in silico approaches, screened on the model through biomolecular drug/signaling-transcriptomic approaches, and validated for long-term efficacy and safety (bottom-up approach), both in a prophylactic and therapeutic scheme.

Regarding the development of new experimental models for the study of liver diseases, two different approaches are being followed: The first focuses on obtaining polarized hepatocytes from urine samples, aiming to have a model for the study of liver diseases that is minimally invasive, can be preserved through freezing, and allows the study of molecular mechanisms of the pathology and drug screening. Alongside this, as a 3D model, organoids from primary adult hepatocytes capable of remaining in culture for over a month are being developed.