Dr. Nerea Matamala

Organoid model of liver disease in Alpha-1 Antitrypsin Deficiency

AAT accumulation into hepatocytes causes AATD in individuals with Z mutation. However, Z AATD is not always associated with liver disease and therefore other factors might contribute to this condition. Since hepatocytes cannot be expanded in vitro and hepatic cell lines do not always accurately replicate the primary cells, liver organoids might be a good alternative to investigate liver disease in AATD. In vitro organoids are three dimensional (3D) cell culture systems in which stem cells self-organize and differentiate into structures that resemble the in vivo tissue in terms of cellular composition and tissue function. This new cell culture tool facilitates modeling of diseases, study of biological processes and testing of new therapies. 


The aim of my proposal is to use human liver organoids as a model system to investigate hepatic disease in AATD. By comparing with healthy human organoids, we will investigate biological processes taking place in the disease such as AAT polymerization, ER stress or changes in gene expression patterns under different stimuli, with special focus on transcriptional regulation of SERPINA1 gene.

Curriculum Vitae Dr. Nerea Matamala

Nerea received her degree in Biology at the University of Valencia and a Master's degree in Biomedical Research at the University of Sevilla. During her PhD she worked in the field of human cancer genetics at the Spanish National Cancer Research Centre (CNIO, Madrid, Spain). Since 2015 she works as postdoctoral fellow on AATD in the Molecular Genetics Unit of the Research Institute for Rare Diseases (Institute of Health Carlos III, ISCIII, Madrid, Spain).

She is involved in different projects related to AATD (identification and characterization of new genetic variants, investigation of gene expression regulation, search of biomarkers of prognosis and treatment). She is also dedicated to the genetic diagnosis of AATD as part of the Reference Laboratory for the Spanish Registry of patients with AATD (REDAAT).

Her project "Organoid model of liver disease in Alpha-1 Antitrypsin Deficiency" aims to further investigate the molecular mechanisms underlying hepatic disease in patients with AATD.

Dr. Nerea Matamala 
Molecular Genetics Unit
Research Institute for Rare Diseases Research (IIER)
Institute of Health Carlos III (ISCIII)
Ctra. Majadahonda-Pozuelo Km.2,200.
Madrid 28220, Spain