Research Project

Project Title:

Exploring the pathophysiology of renal dysfunction in Bardet-Biedl syndrome: a translational study

Project Type:

Translational research

Disease group(s):

Congenital Malformations & Ciliopathies

Project Summary:

Bardet-Biedl syndrome (BBS) is a rare pleiotropic inherited disorder known as a ‘ciliopathy’. Kidney disease is a cardinal feature and is the main cause of mortality and morbidity; no specific therapy is available to date. Recent studies have demonstrated that alterations in cell metabolism are hallmarks of several ciliopathies, including the autosomal dominant polycystic kidney disease (ADPKD),the Nephronophthisis and the autosomal recessive PKD. Recently, altered glycosphingolipid metabolism has been demonstrated to contribute to disease pathophysiology in BBS. Using a metabolomic approach in patients’ urine and sera samples, we aim to characterize the metabolic patterns of a cohort of adult BBS patients (n=50)with different eGFR, compared with aged-gender matched healthy volunteers and CKD patients by other causes. These studies are coupled with in vitro studies, conducted in BBS10 silenced IMCD3 cells and BBS10-overexpressing cells aiming to address: 1) whether BBS depletion causes an intracellular metabolic reprogramming; 2) major BBS10 interactors, that may explain metabolic alterations; 3) whehter targeting potential aberrations may protect from abnormal cilia formation and cytoskeleton organization, known abnormalities of BBS-depleted cells.

Lead principal investigator(s):

Miriam Zacchia, Naples

Co-investigator(s):

Giovambattista Capasso, Naples
Margherita Ruoppolo, Naples

Project Period:

09/2018   -   09/2021

Sponsors:

Local resources

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