Curriculum vitae

  Miguel Prudêncio


     Contribution to Science

A. During the early stages of my scientific career, I worked in the field of metalloprotein biochemistry and enzymology, and on transient protein-protein interactions. During that period, my research focused on the characterization of several metal-containing proteins, particularly bacterial proteins bearing copper centers. I contributed to the elucidation of a hitherto unknown type of copper-containing active site, which had been a matter of debate for years prior to this report. Furthermore, I established a new technique to study protein-protein interactions using paramagnetic NMR spectroscopy. Overall, this work resulted in 16 publications in which I served as the primary or co-investigator.


  1. M. Prudêncio, A.S. Pereira, P. Tavares, S. Besson, I. Cabrito, K. Brown, B. Samyn, B. Devreese, J. Van Beeumen, F. Rusnak, G. Fauque, J. J. G. Moura, M. Tegoni, C. Cambillau and I. Moura (2000) “Purification, Characterization and Preliminary Crystallographic Study of Copper-Containing Nitrous Oxide Reductase from Pseudomonas nautica 617”, Biochemistry, 39, 3899-3907
  2. K. Brown, M. Tegoni, M. Prudêncio, A.S. Pereira, S. Besson, J. J. G. Moura, I. Moura and C. Cambillau (2000) “A Novel Type of Catalytic Copper Cluster in Nitrous Oxide Reductase”, Nature Struct. Biol., 7, 191-195
  3. M.J. Ellis, M. Prudêncio, F.E. Dodd, R.W. Strange, G. Sawers, R.R. Eady, S.S. Hasnain (2002) “Biochemical and Crystallographic Studies of the M144A, D92N and H254F Mutants of the Nitrite Reductase from Alcaligenes xylosoxidans Provide Insight into the Enzyme Mechanism”, J. Mol. Biol., 316, 51-64
  4. M. Prudêncio, J. Rohovec, J.A. Peters, E. Tocheva, M.J. Boulanger, M.E.P. Murphy, H.-J. Hupkes, W. Kosters, A. Impagliazzo, M. Ubbink (2004) “A Caged Lanthanide Complex as a Paramagnetic Shift Agent for Protein NMR”, Chem. Eur. J., 10, 3252-3260

 


B. Upon shifting my research focus to malaria, I became interested in gaining a better understanding of the liver-stage of an infection by Plasmodium, the malaria parasite. Over a period of several years, I made a number of important contributions to this field of study. Among others, I established new methods for the quantification of Plasmodium hepatic infection, employing transgenic parasites expressing fluorescent or luminescent proteins. Besides, I identified new host factors that play a role during infection of liver cells by Plasmodium, including a novel hepatocyte receptor termed SR-BI, and 5 kinases identified in a pioneering RNA interference screen aimed at the liver stage of infection by this parasite. Moreover, I contributed to the determination of the profile of the host cell transcriptome, showing that infected hepatoma cells undergo a coordinated sequence of events throughout malaria liver stage infection. I also studied ion homeostasis during the liver phase of the Plasmodium life cycle, having shown that the parasite induces changes in the activity of ion channels during infection. During this period, which marked my transition towards becoming a fully independent researcher, I published several primary research and review articles, most of which as primary investigator.


  1. M. Prudêncio, A. Rodriguez, M.M. Mota (2006), “The silent path to thousands of merozoites: the Plasmodium liver stage”, Nat. Rev. Microbiol., 4, 849-856
  2. 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
  3. 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
  4. S.S. Albuquerque, C. Carret, A.R. Grosso, A.S. Tarun, X. Peng, S.H.I. Kappe, M. Prudêncio, M.M. Mota (2009) “Host cell transcriptional profiling during malaria liver stage infection reveals a coordinated and sequential set of biological events”, BMC Genomics, 10, 270-282
  5. 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

 


C. As I became increasingly independent, I kept an interest on the liver stage of Plasmodium infection but with a particular emphasis on its potential for anti-Plasmodial intervention. Thus, I carried out pioneering drug screens against Plasmodium liver stages and, in collaboration with various medicinal chemistry research laboratories, I contributed to the identification of novel compounds with anti-Plasmodial activity and to the development of novel hybrid molecules with dual-stage anti-malarial activity.


  1. 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
  2. M. Prudêncio, M.M. Mota, A.M. Mendes (2011) “A toolbox to study liver stage malaria”, Trends Parasitol., 27, 565-574
  3. P. Eaton, V. Zuzarte-Luis, M.M. Mota, N.C. Santos, M. Prudêncio (2012) “Infection by Plasmodium changes shape and stiffness of hepatic cells”, Nanomedicine, 8, 17-19
  4. J. Matos, F.P. da Cruz, E. Cabrita, J. Gut, F. Nogueira, V.E. do Rosário, R. Moreira, P.J. Rosenthal , M. Prudêncio, P. Gomes (2012) “Novel potent metallocenes against liver stage malaria”, Antimicrob. Agents Chemother., 56, 1564-1570
  5. 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
  6. E.R. Derbyshire, M. Prudêncio, M.M. Mota, J. Clardy (2012) "Liver stage malaria parasites vulnerable to diverse chemical scaffolds", Proc. Natl. Acad Sci. USA, 109, 8511-8516



D. As a fully independent scientist, I investigated the development of immune responses against Plasmodium liver stages, showing that innate immunity against liver stage infection is activated by Plasmodium host cell sensors, and that malaria re-infection is inhibited by an innate immune response induced by Plasmodium liver infection. Additionally, I revealed the crucial importance of Plasmodium Puf genes on parasite transmission to the mammalian host, and reported on the role of the Plasmodium rhomboid protease family on the parasite’s liver stage development. I demonstrated the crucial role of GLUT1-mediated glucose uptake during hepatic infection by Plasmodium parasites and, more recently, I identified a novel interaction between Plasmodium EXP-1 and host ApoH proteins. I currently lead several research projects, including a yet unpublished study funded by the Bill & Melinda Gates Foundation and the Malaria Vaccine Initiative towards the development of an innovative strategy for vaccination against malaria.



  1. M. Prudêncio, Maria M. Mota (2013) "Targeting host factors to circumvent anti-malarial drug resistance", Curr. Pharm. Des., 19, 290-299
  2. 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", Nature Medicine, 20, 47-53
  3. 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
  4. C.J.A. Ribeiro, M. Espadinha, M. Machado, J. Gut, L.M. Gonçalves, P.J. Rosenthal, M. Prudêncio, R. Moreira, M.M.M. Santos (2016) "Novel squaramides with in vitro liver stage antiplasmodial activity", Bioorg. Med. Chem., 24, 1786-1792
  5. 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", Cellular Microbiology, doi:10.1111/cmi.12646
  6. 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. *- Corresponding authors
  7. A.M. Mendes, I.S. Albuquerque, M. Machado, J. Pissarra, P. Meireles, M. Prudêncio (2017) "Inhibition of Plasmodium liver infection by ivermectin", Antimicrobial Agents and Chemotherapy, 61, e02005-1613.
  8. A.M. Mendes, A. Scholzen, A.K. Mueller, S.M. Khan, R.W. Sauerwein, M. Prudêncio (2017) “Whole Organism Pre-Erythrocytic Vaccines”, In: Rodriguez, A. and Mota M.M. (Eds) Malaria: immune response to infection and vaccination, Springer International Publishing, Cham, Switzerland


 

Complete List of Published Work (>70 publications):

 

http://www.miguelprudencio.com/publications