Metabolism and Genetics

Group Leader

Ana Paula Leandro

PhD (2001) in Pharmacy (Biochemistry), Universidade de Lisboa
Assistant Professor, Department of Biochemistry and Human Biology

The Research

Our scientific interests focus on the study of metabolic pathways in human health and their disruption either by genetic factors (inborn errors of metabolism), or as a result of external factors namely drug-induced effects. Our key research topics include: mitochondrial metabolism in liver disease, regulation of cell methylation status, non-ER associated conformational genetic disorders, and regulation and gating of channels and transporters. Aiming to contribute to the identification of the mechanisms of pathogenesis, predictive or diagnostic biomarkers and new therapeutic approaches (enzyme replacement, functional rescue of misfolded mutant proteins by small molecular weight compounds, antisense gene therapy and modulators of channels and  transporters), we assembled an integrated experimental platform embracing mutation analysis, protein structural and functional characterization, enzymatic assays, biochemical and biophysical studies of membrane transport, and (MS)-based targeted metabolomics.



Ongoing Projects

Source: Sociedade Portuguesa de Doenças Metabólicas (SPDM)
Title: New approaches for the treatment of Phenylketonuria: Evaluation of human phenylalanine hydroxylase (hPAH) formulations in cellular models.
PI: Paula Leandro
Period: 2016-2018

Source: National PKU Alliance (NPKUA) USA
Title:  Human phenylalanine hydroxlase and nanobiomaterials:  A novel enzyme reposition therapy approach to PKU.
PI: Paulo R. Lino (in collaboration with the iMed.ULisboa Group Nano2B)
Period: 2015-2017

Source: Sociedade Portuguesa de Doenças Metabólicas (SPDM)
Title: Adapting protein homeostasis in inborn errors of metabolism: treatment of severe forms of phenylketonuria.
PI: João Leandro
Period: 2014-2016

Source: Healthy Programme of the EU (2012 12 02)
Title: European network and registry for Homocystinurias and Methylation Defects (EHOD)
PI: Isabel T. Almeida (member of the team)
Period: 2013-2015

Recent Most Relevant Publications

Mendes MI, Smith DE, Vicente JB, Tavares De Almeida I, Ben-Omran T, Salomons GS, Rivera IA, Leandro P*, Blom HJ*. Small aminothiol compounds improve the function of Arg to Cys variant proteins: effect on the human cystathionine β-synthase p.R336C. Hum Mol Genet. 2015; 24(25):7339-48. *Joint last authors.

Madeira A, Moura TF, Soveral G. Aquaglyceroporins: implications in adipose biology and obesity. Cell Mol Life Sci. 2015; 72 (4):759-771.

Coelho AI, Lourenço S, Trabuco M, Silva MJ, Oliveira A, Gaspar A, Diogo L, Tavares de Almeida I, Vicente JB, Rivera I. Functional correction by antisense therapy of a splicing mutation in the GALT gene. Eur J Hum Genet. 2015; 23(4):500-506.

Esse R, Imbard A, Florindo C, Gupta S, Quinlivan EP, Davids M, Teerlink T, Tavares de Almeida I, Kruger WD, Blom HJ, Castro R. Protein arginine hypomethylation in a mouse model of cystathionine β-synthase deficiency. FASEB J. 2014; 28:2686-95.

Aires CC, Cruchten AV, IJlst L, de Almeida IT, Duran M, Wanders RJ, Silva MF. New insights on the mechanisms of valproate-induced hyperammonemia: Inhibition of hepatic N-acetylglutamate synthase activity by valproyl-CoA.  J Hepatol. 2011; 55:426-434.