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Ana Paula Arez
CROSS-CUTTING ISSUE FACILITATOR DIAGNOSTICS and VBD RESEARCH GROUP COORDINATOR
GHTM Group: VBD PhD members, Vector-borne diseases
Ana Paula Arez is Principal Investigator (with Habilitation) at the Medical Parasitology Unit of Institute of Hygiene and Tropical Medicine (IHMT) and at Global Health and Tropical Medicine Center (GHTM) of Universidade NOVA de Lisboa (UNL). She holds a PhD in Biology (2000) and a BSc in Biology (1992) by the Faculty of Sciences, University of Lisbon.
She teaches at Biomedical Sciences, Parasitology and Global Health PhD and MSc courses of IHMT NOVA and supervises or co-supervises Post-docs, PhD and MSc students. She conducts expert review of scientific papers and projects in national and international journal and funding agencies on regular basis.
Presently at IHMT, she is Leader of the GHTM’s Research Group Vector Borne Diseases, Facilitator of the GHTM’s Cross Cutting Issue Diagnostics, Coordinator of the GHTM biobank – Biotropical Resources (BIOTROP) and member of the IHMT’s Scientific Council.
Lines of research: 1) Human host and parasite interactions (human factors of susceptibility/resistance against malaria), 2) Molecular epidemiology of malaria, and 3) Development of new diagnostic methods.
First interest has been malaria transmission dynamics and interaction between different parasites co-infecting the same host; several research projects were conducted in malaria endemic areas (Guinea-Bissau, Cape Verde, Mozambique, Equatorial Guinea). During the studies in Cape Verde, the observation that infected people developed mild symptoms despite their presumptive weak immune status and high parasitaemia aroused interest on the human factors of susceptibility to malaria. Some protective human variants are those involving the Red Blood Cell (RBC)-specific structural proteins and enzymes so research on the association of enzyme disorders on the RBC glycolytic and pentose-phosphate pathways and protection against the Plasmodium parasite were initiated. Population studies showed that malaria infection was the most likely selective pressure shaping both the pklr and tpi genomic regions in individuals from malaria endemic countries.
Looking then at biological processes involved, we hypothesized that the accumulation of 2,3-DPG inside RBC due to pyruvate kinase deficiency could create an unsuitable environment for parasite and could be involved in the protective mechanism. Results showed an inhibition of parasite growth as parasites subjected to the artificial increase of 2,3-DPG in the culture medium produce significantly lower progeny; no effect was observed on the host cell, instead, the metabolic profile of 2,3-DPG treated infected cells became closer to that of non-infected cells.
Studies on other human disorders associated to malaria protection have also been done in collaboration with other researchers, highlighting an ongoing follow-up of a cohort of Angolan children with Sickle Cell Anaemia.
Additionally, being aware that prompt and accurate diagnosis is essential to prevent a mild malaria case from developing into severe disease or death, studies to develop new simple, rapid, and sensitive molecular diagnostic tests to characterize malaria infected isolates are ongoing to develop a platform test for the rapid detection of markers associated to antimalarial drug resistance.
- Balau, A., Sobral, D., Abrantes, P., Santos, I., Mixão, V., Gomes, J.P., Antunes, S., Arez, A.P. (2023). Differential Gene Expression of Malaria Parasite in Response to Red Blood Cell-Specific Glycolytic Intermediate 2,3-Diphosphoglycerate (2,3-DPG). International Journal of Molecular Sciences, 24, 16869. doi:10.3390/ijms242316869
- Carvalho, M., Medeiros, M.M., Morais, I., Lopes, C.S., Balau, A., Santos, N.C., Carvalho, F.A., Arez, A.P. (2023). 2,3-Diphosphoglycerate and the Protective Effect of Pyruvate Kinase Deficiency against Malaria Infection—Exploring the Role of the Red Blood Cell Membrane. International Journal of Molecular Sciences, 24, 1336. http://doi.org/10.3390/ijms24021336
- Morais, I., Medeiros, M.M., Carvalho, M., Morello, J., Teixeira, S.M., Maciel, S., Nhantumbo, J., Balau, A., Rosa, M.T.G., Nogueira, F., Rodrigues, J.A., Carvalho, F.A., Antunes, A.M.M., Arez, A.P. (2022). Synthetic Red Blood Cell-Specific Glycolytic Intermediate 2,3-Diphosphoglycerate (2,3-DPG) Inhibits Plasmodium falciparum Development In Vitro. Frontiers in Cellular and Infection Microbiology, 12, 840968. http://doi.org/10.3389/fcimb.2022.840968
- Machado, P., Manco, L., Gomes, C., Mendes, C., Fernandes, N., Salomé, G., Sitoe, L., Chibute, S., Langa, J., Ribeiro, L., Miranda, J., Cano, J., Pinto, J., Amorim, A., do Rosário, V.E., Arez, A.P. (2012). Pyruvate kinase deficiency in sub-Saharan Africa: identification of a highly frequent missense mutation (G829A;Glu277Lys) and association with malaria. PLoS ONE, 7: e47071. http://doi.org/10.1371/journal.pone.0047071
- Machado, P., Pereira, R., Rocha, A.M., Manco, L., Fernandes, N., Miranda, J., Ribeiro, L., do Rosário, V.E., Amorim, A., Gusmão, L., Arez, A.P. (2010). Malaria: looking for selection signatures in the human PKLR gene region. British Journal of Haematology, 149: 775-784. http://doi.org/10.1111/j.1365-2141.2010.08165.x