He joined ISGlobal as an ICREA Research Professor in 2007 and recently co-ascribed to the Institut Germans Trias I Pujol (IGTP). He is presently the President of the Grupo Español de Investigación e Innovación en Vesículas Extracelulares (GEIVEX) and Co-Founder of Innovex Therapeutics SL, the first Spanish company using extracellular vesicles for the development of vaccines and diagnostics.
Líneas de investigación
- Molecular bases of the pathology in P. vivax malaria. We have contributed to the identification and characterization of variant genes in P. vivax malaria (del Portillo et al., Nature 2001; Fernandez-Becerra et al., Mol Microbiol 2005; Carlton et al, del Portillo et al., Nature 2008; Fernandez-Becerra et al., Trends Parasitol 2009; Lopez et al., BMC Genomics 2013). Cryptic infections and exosomes. Our investigations indicate that cryptic niches outside the liver, in particular in the bone marrow and the spleen, can represent a major source of hypnozoites-unrelated recrudescences. We are presently exploring the role of exosomes as intercellular vehicles between the bone marrow and the spleen and the molecular basis of cryptic infections in P. vivax (Baro et al., 2018 PNTD; De Niz et al., 2016 Nat Comm; Siqueira et al., 2012 PNTD; Martin-Jaular et al., 2011 Cell Microbiol).Reticulocyte-derived exosomes (Rex) vaccines against P. vivax. We previously found that exosomes derived from reticulocytes infected with malaria parasites can induce a long-lasting protective immune response. More recently, we determined the proteome of plasma-derived exosomes from P. vivax patients and of human reticulocyte exosomes and showed that they contain MHC class I molecules that are actively uptaken by human dendritic cells. We are pursuing efforts to “tailor” human Rex with P. vivax antigens and determine their potential as a new delivery platform for P. vivax vaccines. (Martin-Jaular et al., Plos One 2011, Diaz-Varela et al., Sci. Rep 2018).Hypnozoite biomarker discovery. The human liver-chimeric FRG-KO-(huHep) mice is a robust P. vivax infection model for exo-erythrocytic development of liver stages, including hypnozoites (latent hepatic stages causing clinical relapses). Since exosomes are recognized for carrying potential biomarkers of disease, we are using mass-spectrometry to identify new markers of asymptomatic hypnozoite carriers and develop microfluidic devices for point of care diagnostics (Gualdron-Lopez et al., Front Microbiol, 2018).
- Martin-Jaular L, et al., and del Portillo HA. Spleen-Dependent Immune Protection Elicited by CpG Adjuvanted Reticulocyte-Derived Exosomes from Malaria Infection Is Associated with Changes in T cell Subsets' Distribution. Front Cell Dev Biol. 2016 Nov 16;4:131.
- De Niz M, Burda PC, Kaiser G, del Portillo HA, Spielmann T, Frischknecht F, Heussler VT. Progress in imaging methods: insights gained into Plasmodium biology. Nat Rev Microbiol. 2017 Jan;15(1):37-54.
- de Menezes-Neto A, et al., and del Portillo HA. Size-exclusion chromatography as a stand-alone methodology identifies novel markers in mass spectrometry analyses of plasma-derived vesicles from healthy individuals. J Extracell Vesicles. 2015;4:27378
- Martin-Jaular L, et al., and del Portillo HA. Exosomes from Plasmodium yoelii-infected reticulocytes protect mice from lethal infections. PLoS One. 2011;6(10):e26588.
- Mueller I, et al., and del Portillo HA. 2009. Key gaps in the knowledge of Plasmodium vivax, a neglected human malaria parasite. Lancet Infectious Diseases, 9(9): 555-566.
- del Portillo HA, et al., 2001. A superfamily of variant genes encoded in the subtelomeric region of Plasmodium vivax. Nature, 410: 839-842.
- Carlton J, et al., del Portillo HA, et al. and Fraser-Liggett CM. 2008. Comparative genomics of the neglected human parasite Plasmodium vivax. Nature, 455: 757-763.