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, such as inborn errors of metabolism, or as a result of external factors namely drug-induced effects. The group key research topics include: mitochondrial metabolism in liver disease, modulation of protein acetylation and cell bioenergetics, regulation of cell methylation status, non-ER associated conformational genetic disorders, and regulation and gating of channels and transporters. Our main goals comprise the identification of pathogenic mechanisms, predictive or diagnostic biomarkers and new therapeutic approaches namely, enzyme replacement, rescue of misfolded variant proteins by small molecules, antisense gene therapy, identification of regulatory mechanisms and disclosure of chemical modulators of membrane channels and transporters. To achieve our aims, we assembled an integrated experimental platform embracing mutation analysis, protein structural/functional characterization, biochemical and biophysical studies of membrane transport, and (MS)-based targeted metabolomics.



Ongoing Projects

Source: Sociedade Portuguesa de Doenças Metabólicas (SPDM)
Title: Next-generation sequencing for the molecular characterization of pyruvate dehydrogenase complex deficiency due to primary and secondary causes.
PI: Isabel Rivera
Period: 2017-2019

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: EU-COST Action BM1406
Title: Ion channels and immune response toward a global understanding of immune cell physiology and for new therapeutic approaches IONCHAN-IMMUNRESPON
PI: Graça Soveral (management committee)
Period: 2015-2018

Source: National PKU Alliance (NPKUA) USA
Title:  Human phenylalanine hydroxylase and nanobiomaterials:  A novel enzyme reposition therapy approach to PKU.
PIs: Paula Leandro (Met&Gen) and Antonio J Almeida (Nano2B)
Period: 2015-2017



Recent Most Relevant Publications

Pinheiro A, Silva MJ, Florindo C, Pavlu-Pereira H, Barroso M, Marques B, Correia H, Oliveira A, Gaspar A, Tavares de Almeida I, Rivera I. Complex genetic findings in a female patient with pyruvate dehydrogenase complex deficiency: null mutations in PDHX gene associated with unusual expression of the testis-specific PDHA2 gene in her somatic cells. Gene 2016; 591: 417-424.

Moedas MF, van Cruchten AG, IJlst L, Kulik W, de Almeida IT, Diogo L, Wanders RJA and Silva MFB; Transient decrease of hepatic NAD+ and amino acid alterations during treatment with valproate: new insights on drug-induced effects in vivo using targeted MS-based metabolomics. Metabolomics 2016; 12:142.

Barroso M, Kao D, Blom HJ, Tavares de Almeida I, Castro R, Loscalzo J, Handy DE. S-adenosylhomocysteine induces inflammation through NFkB: A possible role for EZH2 in endothelial cell activation. Biochim Biophys Acta  2016; 1862:82-92.

de Almeida A, Mósca AF, Wragg D, Wenzel M, Kavanagh P, Barone G, Leoni S, Soveral G, Casini A. The mechanism of aquaporin inhibition by gold compounds elucidated by biophysical and computational methods. Chem Commun (Camb) 2017; 53: 3830-33.

Bonito CA, Nunes J, Leandro J, Louro F, Leandro P, Ventura FV, Guedes RC. Unveiling the Pathogenic Molecular Mechanisms of the Most Common Variant (p.K329E) in Medium-Chain Acyl-CoA Dehydrogenase Deficiency by in Vitro and in Silico Approaches. Biochemistry 2016; 55: 7086-98.

Group Members

Master Students

  • Raquel Lopes
  • Carolina Costa
  • Duarte Lopes
  • Rute Martins
  • André Gomes
  • António Lemos
  • Andreia Almeida
  • João Caio
  • Sandra Banha