Rui Castro

Liver Disease Diagnostics and Therapeutics

We study the role of microRNAs and other modulators of gene expression in liver disease pathogenesis, while exploring their use in disease diagnosis, treatment, monitoring and prevention.

microRNAs are small non-coding RNAs that act as post-transcriptional regulators of gene expression. The aberrant expression of microRNAs or disruption of its biogenesis associates with many human diseases. In addition, microRNAs can be found in peripheral circulation, typically associated with proteins or within extracellular vesicles (EVs), highlighting their potential as both endocrine signaling molecules and disease biomarkers.

Our lab is studying how changes in complex miRNA regulatory networks can lead to the development of human pathologies, focusing on chronic liver diseases associated with the metabolic syndrome, particularly non-alcoholic fatty liver disease (NAFLD), as well as hepatocellular carcinoma and cholangiocarcinoma.

We aim to elucidate the function of miRNAs and EVs in the liver and in inter-organ communication with the adipose tissue and skeletal muscle; and to explore their potential as circulating biomarkers and therapeutic targets. To this end, we employ advanced biochemical, molecular and cellular tools upon well-established in vitro and in vivo models of disease, as well as human patient biopsies and clinical data, combined in multi-layered, mechanism-based translational approaches.

We have a large network of multidisciplinary partners in clinical science and the pharma industry, assisting us in translating our discoveries to the clinical setting and, ultimately, bring microRNA-associated health technologies to patients. Likewise, through our leadership positions in several European medical organizations, we seek to incorporate patient insights in our research and to involve the general public in science, pivotal to the discovery and development of better medicines.

Simão AL, Afonso MB, Rodrigues PM, Gama-Carvalho M, Machado MV, Cortez-Pinto H, Rodrigues CMP, Castro RE. Skeletal muscle miR-34a/SIRT1:AMPK axis is activated in experimental and human non-alcoholic steatohepatitis. J Mol Med 2019; 97: 1113-1126. DOI: 10.1007/s00109-019-01796-8
Hernández-Alvarez MI, Sebastián D, Vives S, Ivanova S, Bartoccioni P, Kakimoto P, Plana N, Veiga SR, Hernández V, Vasconcelos N, Peddinti G, Adrover A, Jové M, Pamplona R, Gordaliza-Alaguero I, Calvo E, Cabré N, Castro R, Kuzmanic A, Boutant M, Sala D, Hyotylainen T, Orešič M, Fort J, Errasti-Murugarren E, Rodrígues CMP, Orozco M, Joven J, Cantó C, Palacin M, Fernández-Veledo S, Vendrell J, Zorzano A. Deficient endoplasmic reticulum-mitochondrial phosphatidylserine transfer causes liver disease. Cell 2019; 177: 881-895.e17. DOI: 10.1016/j.cell.2019.04.010
Rodrigues PM, Afonso MB, Simão AL, Carvalho CC, Trindade A, Duarte A, Borralho PM, Machado MV, Cortez-Pinto H, Rodrigues CMP, Castro RE. miR-21 ablation and obeticholic acid ameliorate nonalcoholic steatohepatitis in mice. Cell Death Dis 2017; 8: e2748. DOI: 10.1038/cddis.2017.172
Rodrigues PM, Afonso MB, Simão AL, Borralho PM, Rodrigues CMP, Castro RE. Inhibition of NF-κB by deoxycholic acid induces miR-21/PDCD4-dependent hepatocellular apoptosis. Sci Rep 2015; 5: 17528. DOI: 10.1038/srep17528.
Castro RE, Ferreira DM, Afonso MB, Borralho PM, Machado MV, Cortez-Pinto H, Rodrigues CMP. miR-34a/SIRT1/p53 is suppressed by ursodeoxycholic acid in the rat liver and activated by disease severity in human non-alcoholic fatty liver disease. J Hepatol 2013; 58: 119-25. DOI: 10.1016/j.jhep.2012.08.008

Rui Castro

Group Leader


Phone: (+351) 217946400 (Ext. 14509)

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Faculdade de Farmácia da Universidade de Lisboa | Av. Professor Gama Pinto
1649-003 Lisboa | Portugal

Phone | +351 217 946 400
Fax | +351 217 946 470
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