for Physicians
for Patients

Research Project

Project Title:

Systems biology to discover pathophysiologic mechanisms and therapeutic targets in Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis

Project Type:

 Translational research

Disease group(s):

 Tubulopathies

Project Summary:

 The aims of this project are 1) To verify the results obtained in whole exome sequencing (WES) and miRNA microarray assays in
patient samples, 2) Systems biology analysis and mathematical modelling to identify key proteins and pathways in disease
progression from data generated by WES and microarrays in patient samples, 3) Serial collection of urine from FHHNC patients to
create a sample collection that allows us to validate the diagnostic and prognostic biomarkers identified and to observe their evolution
over time and the correlation with the evolution of the disease, 4) To identify therapeutic targets for biocomputational drug design (de
novo discovery) and repositioning (drug reprofiling) and 5) To produce a cellular model of the disease with mutations in the CLDN16 and
CLDN19 genes where the results obtained in patients and computations can be verified, as well as to test possible therapeutic
strategies.
This longitudinal study requires the collaboration of several hospitals located throughout Spain that will provide clinical data and
biological samples of patients diagnosed with HFHNC, both those included in the first cohort (serial urine samples) and new patients to
be included in the validation cohort.
The analysis by systems biology and mathematical modelling, from genomic data and microarrays will allow to know which biological
and molecular processes are altered in the disease, leading to the identification of new therapeutic targets and/or biomarkers of the
disease. The data obtained from this analysis will be verified in the cellular models of the disease generated. At the same time,
possible therapeutic strategies will be tested.

Lead principal investigator(s):

 Gema Ariceta, Barcelona

Co-investigator(s):

 Marina Muñoz, Barcelona
Mercedes Lopez, Barcelona
Alejandro Cruz, Barcelona
Monica Vall-Palomar, Barcelona, Spain

Project Period:

 01/2019   -   12/2022

Sponsors:

 National funding agency
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