Name of the Group:
Liver-Brain Unit “Rita Moretti”
Silvia Gazzin (Senior Scientist)
John Paul Llido (PhD Student)
Camilla Dalla Verde (PhD Student)
Giorgia Valerio (Master Degree Student)
Cristina Bellarosa (Senior Scientist)
Benedetta Blarasin (PhD Student)
Serena Buzzi (Master Degree Student)
The group is active on three different research lines:
- Neurological damage in severe neonatal jaundice (kernicterus)
- Parkinson's disease
- the development of new tools for the study of liver diseases
In the field of kernicterus, we are currently investigating A) the epigenetic impact of bilirubin on brain development, which presents transient effects (e.g. on differentiation, synaptogenesis, plasticity and repair, energy metabolism, etc.) localized to specific brain structures, which a transcriptomic imprinting in motor areas. The genes identified, among other things, could explain the higher frequency of neuropsychiatric syndromes in adulthood for people who have had neonatal jaundice. B) We are also investigating the genetic variables potentially responsible for the symptomatic variability observed in the clinic, with the final aim of creating a diagnostic chip that allows a more precise identification of newborns at risk of neurological damage, with an optimization and individualization of care. C) Based on the acquired biomolecular knowledge, pharmacological approaches (primarily curcumin) are being validated that are able to counteract neurological damage despite the presence of severe jaundice. These approaches are easy to implement even in low-incoming countries where neonatal jaundice is still a cause of neonatal death.
A parallel project concerns the role of calcium homeostasis in bilirubin neurotoxicity, in order to find new therapeutic approaches to prevent permanent neurological damage in newborns affected by severe and prolonged hyperbilirubinemia.
In the field of neurodegenerative diseases, following the identification of the determining effect of TNF-alpha in the death of dopaminergic neurons, prevented by administering low doses of bilirubin, work is underway in two directions: 1) In collaboration with the University of Turin, work is underway on the validation of a nano delivery system of bilirubin (nanobubbles) to the substantia nigra. 2) An alternative in vitro model of slow degeneration of dopaminergic neurons in Parkinson's disease is also being created to be used as a platform for screening compounds with anti-inflammatory action. The compounds will be selected through an in silico approach, screened on the model through biomolecular approaches of drug/signalling-transcriptomics, and validated for long-term efficacy and safety (bottom-up approach), both in a prophylactic and therapeutic regimen.
Regarding the development of new experimental models for the study of liver diseases, two different approaches are being followed. The first is focused on obtaining polarized hepatocytes from urine samples, in order to have a model for the study of liver diseases that can be obtained in a minimally invasive way, preserved by freezing and that allows the study of the molecular mechanisms of the pathology as well as drug screening. In addition to this, as a 3D model, organoids are being developed from adult primary hepatocytes capable of remaining in culture for over a month.
