Miguel Prudêncio Lab

Infecção por Plasmodium & Intervenções Anti-maláricas

Os nossos interesses científicos englobam uma vasta gama de assuntos na área da Malária, com particular ênfase na fase hepática da infecção. Estamos interessados em elucidar diversos aspectos da biologia da infeção pelo parasita Plasmodium, identificar novas interações parasita-hospedeiro e desenvolver novas estratégias anti-malária baseadas em fármacos e vacinas.

Equipa de Investigação

Áreas de Investigação

• Compreender os mecanismos moleculares de transporte e homeostase de nutrientes e iões durante o desenvolvimento do Plasmodium em células hepáticas.
• Elucidar o papel do metabolismo dos ácidos biliares e dos mecanismos de sinalização por receptores nucleares no contexto de uma infecção hepática por Plasmodium.
• Avaliar novos compostos em termos da sua eficiência contra a fase hepática do Plasmodium.
• Desenvolver uma nova vacina pré-eritrocitária contra a malária.
• Investigar a influência recíproca de co-infeções de Plasmodium e Trypanosoma.

Projetos de Investigação em Curso

2020/2023 AMAZING – toxinas de serpentes da AMAZónia: Investigação na valorização de biorrecursos. Coordenação: Miguel Prudêncio. Agência Financiadora: Fundação para a Ciência e a Tecnologia.

2019/2021 Generation, characterization and in vivo evaluation of a novel live malaria vaccine. Coordenação: Miguel Prudêncio. Agência Financiadora: GSK - OpenLab.

2018/2021 Enabling strategies for enhanced whole-sporozoite malaria vaccines. Coordenação: Miguel Prudêncio. Agência Financiadora: Fundação para a Ciência e a Tecnologia.

2018/2021 A multitarget strategy to hit all stages of the Plasmodium life-cycle. Coordenação: Miguel Prudêncio. Agência Financiadora: Fundação para a Ciência e a Tecnologia.

Prémios

2014 EVERIS Entrepreneurs Award, Grand Finalist, April 2014, Madrid, Spain

2013 National BES Innovation Contest, 1st Prize for the Health Track and Winner of the Grand Prize, Concurso Nacional de Inovação do Banco Espirito Santo, November 2013, Lisboa, Portugal

2013 Building Global Innovators - ISCTE-IUL MIT-Portugal Venture Competition, Honorary Mention Health Track, November 2013, Lisboa, Portugal

2008 Amélia da Silva de Mello Award for Health Sciences, 1st Prize for the work entitled "Host SR-BI plays a dual role in the establishment of malaria liver infection", José de Mello ▪ Saúde, September 2008, Lisboa, Portugal

2007 CESPU International Research Award, 1st Prize for the work entitled "SR-BI plays a dual role in the establishment of malaria liver infection", Cooperativa de Ensino Superior Politécnico e Universitário, November 2007, Porto, Portugal

2004 Marie Curie Reintegration Grant

2001 Marie Curie Fellowship

Publicações Selecionadas

Reuling IJ, Mendes AM, de Jong GM, Fabra-García A, Nunes-Cabaço H, van Gemert GJ, Graumans W, Coffeng LE, de Vlas SJ, Yang ASP, Lee CK, Wu Y, Birkett AJ, Ockenhouse CF, Koelewijn R, van Hellemond JJ, van Genderen PJJ, Sauerwein RW, Prudêncio M (2020). Safety and efficacy of a genetically modified rodent malaria parasite against Plasmodium falciparum malaria: an open-label randomized phase 1/2a trial. Science Translational Medicine 12:eaay2578.

Meireles P, Brás D, Fontinha D, Chora AF, Serre K, Mendes AM, Prudêncio M (2020). Elimination of Hepatic Rodent Plasmodium Parasites by Amino Acid Supplementation. iScience 23(12):101781.

M. Sanches-Vaz, A. Temporão, R. Luis, H. Nunes-Cabaço, A.M. Mendes, S. Goellner, T. Carvalho, L.M. Figueiredo, M. Prudêncio (2019) "Trypanosoma brucei infection protects mice against malaria", PLoS Pathogens, in press.

R. Azevedo, A.M. Mendes, M.Prudêncio (2019) "Inhibition of Plasmodium sporogonic stages by ivermectin and other avermectins", Parasites & Vectors, in press.

F. Arez, S. Rebelo, D. Fontinha, D. Simão, T.R. Martins, M. Machado, C. Fischli, C. Oeuvray, L. Badolo, M. J. T. Carrondo, M. Rottmann, T. Spangenberg, C. Brito, B. Greco, M. Prudêncio, P.M. Alves (2019) “Flexible 3D cell-based platforms for the discovery and profiling of novel drugs targeting Plasmodium hepatic infection”, ACS Infect. Dis., in press.

K. Wolanin, D. Fontinha, M. Sanches‐Vaz, B. Nyboer, Kirsten Heiss, A.-K. Mueller, M. Prudêncio (2019) “A crucial role for the C‐terminal domain of exported protein 1 during the mosquito and hepatic stages of the Plasmodium berghei life cycle”, Cell. Microbiol., e13088.

A.M. Mendes, I.J. Reuling, C.M. Andrade, T.D. Otto, M. Machado, F. Teixeira, J. Pissarra, N. Gonçalves-Rosa, D. Bonaparte, J. Sinfrónio, M. Sanders, C.J. Janse, S.M. Khan, C.I. Newbold, M. Berriman, C. Lee, Y. Wu, C.F. Ockenhouse, R.W. Sauerwein, M. Prudêncio (2018) "Pre-Clinical Evaluation of a P. berghei-Based Whole-Sporozoite Malaria Vaccine Candidate", NPJ Vaccines, 3, 54.

A.M. Mendes, M. Machado, N. Gonçalves-Rosa, I.J. Reuling, L. Foquet, C. Marques, A.M. Salman, A.S.P. Yang, K.A. Moser, A. Dwivedi, C.C. Hermsen, B. Jiménez-Díaz, S. Viera, J.M. Santos, I. Albuquerque, S.N. Bhatia, J. Bial, I. Angulo-Barturen, J.C. Silva, G. Leroux-Roels, C.J. Janse, S.M. Khan, M.M. Mota, R.W. Sauerwein, M. Prudêncio (2018) "A Plasmodium berghei Sporozoite-Based Vaccination Platform Against Human Malaria", NPJ Vaccines, 3, 33.

M. Machado, M. Sanches-Vaz, J.P. Cruz, A.M. Mendes, M. Prudêncio (2017) "Inhibition of Plasmodium hepatic infection by antiretroviral compounds", Front. Cell. Infect. Microbiol., 7, doi: 10.3389/fcimb.2017.00329.

P. Meireles, A.M. Mendes, R.I. Aroeira, B.C. Mounce, M. Vignuzzi, H.M. Staines, M. Prudêncio (2017) "Uptake and metabolism of arginine impact Plasmodium development in the liver", Sci. Rep., 7, 4072.

R. Azevedo, M. Markovic, M. Machado, B. Franke-Fayard, A.M. Mendes, M. Prudêncio (2017) "A bioluminescence method for in vitro screening of Plasmodium transmission-blocking compounds", Antimicrob. Agents Chemother., 61, 202699-16.

C.S. Cunha, B. Nyboer, K. Heiss, M. Sanches-Vaz, D. Fontinha, E. Wiedtke, D. Grimm, J.M. Przyborski, M.M. Mota, M. Prudêncio, A.K. Mueller (2017) "P. berghei EXP-1 Interacts with Host Apolipoprotein H during Plasmodium Liver Stage Development", Proc. Natl. Acad. Sci. USA, 114, E1138-E1147.

A.M. Mendes, I.S. Albuquerque, M. Machado, J. Pissarra, P. Meireles, M. Prudêncio (2017) "Inhibition of Plasmodium liver infection by ivermectin", Antimicrob. Agents Chemother., 61, e02005-16.

P. Meireles, J. Sales-Dias, C.M. Andrade, J. Mello-Vieira, L. Mancio-Silva, J.P. Simas, H.M. Staines, M. Prudêncio (2016) "GLUT1-mediated glucose uptake plays a crucial role during Plasmodium hepatic infection", Cell. Microbiol., doi:10.1111/cmi.12646.

M.D. Lewis, J. Behrends, C.S. Cunha, A.M. Mendes, F. Lasitschka, K. Heiss, T.W.A. Kooij, M.Prudêncio, F.Frischknecht and A.-K. Mueller (2015), "Chemical attenuation of Plasmodium in the liver modulates severe malaria disease progression", Journal of Immunology, in press.

C.A.B. Rodrigues, R.F.M. Frade, I.S. Albuquerque, M.J. Perry, J. Gut, M. Machado, P.J. Rosenthal, M. Prudêncio, C.A.M. Afonso, R. Moreira (2015), "Targeting the Erythrocytic and Liver Stages of Malaria Parasites with s-Triazine-Based Hybrids", ChemMedChem, in press.

P. Liehl, P. Meireles, I.S. Albuquerque, M. Pinkevych, F. Baptista, M.M. Mota, M.P. Davenport, M. Prudêncio (2015), "Innate immunity induced by Plasmodium liver infection inhibits malaria reinfections", Infection and Immunity, 83, 1172-1180.

P. Liehl, V. Zuzarte-Luís, J. Chan, T. Zillinger, F. Baptista, D.l Carapau, M. Konert, K. Hanson, C. Carret, C. Lassnig, M. Müller, U. Kalinke, M. Saeed, A.F. Chora, D.T. Golenbock, B. Strobl, M. Prudêncio, L.P. Coelho, S.H. Kappe, G. Superti-Furga, A. Pichlmair, A.M. Vigário, C.M. Rice, K.A. Fitzgerald, W. Barchet, M.M. Mota (2014) "Host cell sensors for Plasmodium activate innate immunity against liver stage infection", Nat. Med., 20, 47-53.

T. Rodrigues, F.P. da Cruz, M. Lafuente-Monasterio, D. Gonçalves, A. Ressurreição, A.R. Sitoe, M.R. Bronze, J.Gut, G. Schneider, M.M. Mota, P.J. Rosenthal, M. Prudêncio, F.-J. Gamo, F. Lopes, R. Moreira (2013) "Quinolon-4(1H)-imines are Potent Antiplasmodial Drugs Targeting the Liver Stage of Malaria", J. Med. Chem., 56, 4811-4815.

E. Dempsey, M. Prudêncio, B.J. Fennell, C.S. Gomes-Santos, J.W. Barlow, A. Bell (2013) "Antimitotic herbicides bind to an unidentified site on malarial parasite tubulin and block development of liver-stage Plasmodium parasites", Mol. Biochem. Parasitol., 188, 116-127. Highlighted as Feature Article on Malaria Nexus.

J. Lin, P. Meireles, M. Prudêncio, S. Engelmann, T. Annoura, M. Sajid, S. Chevalley‐Maurel, J. Ramesar, C. Nahar, C.M.C. Avramut, A.J. Koster, K. Matuschewski, A.P. Waters, C.J. Janse, G.R. Mair, S.M. Khan (2013) "Loss‐of‐Function Analyses Defines Vital and Redundant Functions of the Plasmodium Rhomboid Protease Family", Mol. Microbiol., 88, 318-338.

B.C. Pérez, C. Teixeira, I.S. Albuquerque, J. Gut, P.J. Rosenthal, J.R.B. Gomes, M. Prudêncio, P. Gomes (2013) "N-cinnamoylated chloroquine analogues as dual-stage antimalarial leads", J. Med. Chem., 56, 556-567.

M. Prudêncio, Maria M. Mota (2013) "Targeting host factors to circumvent anti-malarial drug resistance", Curr. Pharm. Des., 19, 290-299.

F.P. da Cruz, C. Martin, K. Buchholz K, M.J. Lafuente-Monasterio, T. Rodrigues, B. Sönnichsen, R. Moreira, F.J. Gamo, M. Marti, M.M. Mota, M. Hannus, M. Prudêncio (2012) "Drug Screen Targeted at Plasmodium Liver Stages Identifies a Potent Multi-Stage Anti-Malarial Drug", J. Inf. Dis., 205, 1278-1286, Evaluated by Faculty of 1000 Biology and Medicine

M. Prudêncio, M.M. Mota, A.M. Mendes (2011) "A toolbox to study liver stage malaria", Trends Parasitol., 27, 565-574 (Review), Selected by MalariaNexus.

R. Capela, G.G. Cabal, P.J. Rosenthal, J. Gut, M.M. Mota, R. Moreira, F. Lopes, M. Prudêncio (2011) "Design and evaluation of primaquine-artemisinin hybrids as a multistage antimalarial strategy", Antimicrob. Agents Chemother., 55, 4698-4706.

K. Slavic, M.J. Delves, M. Prudêncio, A.M. Talman, U. Straschil, E.T. Derbyshire, Z. Xu, R.E. Sinden, M.M. Mota, C. Morin, R. Tewari, S. Krishna, H.M. Staines (2011) "Use of a Selective Inhibitor To Define the Chemotherapeutic Potential of the Plasmodial Hexose Transporter in Different Stages of the Parasite's Life Cycle", Antimicrob. Agents Chemother., 55, 2824-2830.

I.H. Ploemen, M. Prudêncio, B.G. Douradinha, J. Ramesar, J. Fonager, G.J. van Gemert, A.J. Luty, C.C. Hermsen, R.W. Sauerwein, F.G. Baptista, M.M. Mota, A.P. Waters, I. Que, C.W. Lowik, S.M. Khan, C.J Janse, B.M. Franke-Fayard (2009) "Visualisation and quantitative analysis of the rodent malaria liver stage by real time imaging", PLoS ONE, 4, e7881.

M. Prudêncio, E.T. Derbyshire, C.A. Marques, S. Krishna, M.M. Mota, H.M. Staines (2009) "Plasmodium berghei-infection induces volume-regulated anion channel-like activity in human hepatoma cells", Cell. Microbiol., 11, 1492-1501.

M. Prudêncio, M.J. Lehmann (2009) "Illuminating the host - How RNAi screens shed light on host-pathogen interactions", Biotechnol. J., 4, 826-837.

M. Prudêncio, C.D. Rodrigues, M. Hannus, C. Martin, E. Real, L .A. Gonçalves, C. Carret, R. Dorkin, I. Röhl, K. Jahn-Hoffmann, A.J.F. Luty, R. Sauerwein, C.J. Echeverri, M.M. Mota (2008) "Kinome-Wide RNAi Screen Implicates at Least 5 Host Hepatocyte Kinases in Plasmodium Sporozoite Infection", PLoS Pathogens, 4, 1-15.

C.D. Rodrigues, M. Hannus, M. Prudêncio, C. Martin, L.A. Gonçalves, S. Portugal, S. Epiphanio, A. Akinc, P. Hadwiger, K. Jahn-Hofmann, I. Röhl, G.J. van Gemert, J.F. Franetich, A.J. Luty, R. Sauerwein, D. Mazier, V. Koteliansky, H.P. Vornlocher, C.J. Echeverri, M.M. Mota (2008) "Host Scavenger Receptor SR-BI Plays a Dual Role in the Establishment of Malaria Parasite Liver Infection", Cell Host & Microbe, 11, 4, 271-282.

O. Silvie, M.M. Mota, K. Matuschewski, M. Prudêncio (2008) "Interactions of the malaria parasite and its mammalian host", Curr. Opin. Microbiol., 11, 352-359.

M. Prudêncio, C.D. Rodrigues, R. Ataíde, M.M. Mota (2008), "Dissecting in vitro host cell infection by Plasmodium sporozoites using flow cytometry", Cell. Microbiol., 10, 218-224.

M. Prudêncio, M.M. Mota (2007), "To migrate or to invade: those are the options", Cell Host & Microbe, 2, 286-288.

M. Prudêncio, A. Rodriguez, M.M. Mota (2006), "The silent path to thousands of merozoites: the Plasmodium liver stage", Nat. Rev. Microbiol., 2006, 4, 849-856.

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