ZFIN ID: ZDB-PERS-980624-6
Málaga-Trillo, Edward
Email: edward.malaga@upch.pe
URL: http://bit.ly/ZebrafishLabPeru
Affiliation: Málaga-Trillo Lab
Address: Department of Biology Universidad Peruana Cayetano Heredia Lima 15102, PERÚ Tel: +51 1 319-0000 Ext. 233246
Country: Peru
Phone: +51 1 319-0000 Ext. 233246

Dr. Edward Málaga-Trillo was born in Lima, Perú, completed his undergraduate studies in Biology at Universidad Peruana Cayetano Heredia (UPCH) and carried out his Ph.D. in Microbiology and Immunology at the University of Miami School of Medicine and the Max-Planck-Institut für Biologie in Tübingen, Germany. After postdoctoral trainings in Evolutionary Genomics and Developmental Neurobiology at the University of Konstanz, Germany, he was appointed Wissenschaftlicher Assistent (Assistant Professor) there and, upon completing the German Habilitation, Privatdozent (Adj. Associate Professor) in Developmental Neurobiology. Throughout his career, he acquired specialized training in fish genetic manipulations (Stirling, Scotland), Molecular Evolution (Hayama, Japan), Evolutionary Genomics (Eugene, USA) and Developmental Genetics of Zebrafish (Woods Hole, USA). His published work focuses on the cellular and molecular basis of neuronal degeneration and regeneration. Dr. Málaga-Trillo’s uses zebrafish as a model organism to study molecular mechanisms of neurodegeneration. In 2015 he returned as Full Professor to UPCH, where he set up the first Peruvian zebrafish laboratory at the Developmental Neurobiology Research Unit. Since 2018 he is President of the Latin American Zebrafish Network (LAZEN).

Neurodegenerative conditions like Alzheimer’s, Parkinson’s and prion disease result from the misfolding and aggregation of key neuronal proteins. In fact, the striking loss of cognitive and motor abilities in these age-related illnesses is frequently linked to the appearance of abnormal protein deposits in neurons. However, the presence of plaques and tangles in elderly brains is not a precondition for neurodegeneration. Rather, neuronal damage is triggered by small precursors of these rogue proteins decades before brain deposits and clinical symptoms become evident.

Our research has two continuing goals:

-understanding the cellular and molecular mechanisms by which misfolded protein oligomers induce early neurotoxicity in vivo
-transforming this information into novel drug screening methodologies to identify anti-neurodegeneration compounds

To pursue these goals, we employ cell biological, biochemical and behavioral approaches in genetically and pharmacologically manipulated zebrafish embryos. These small vertebrates offer key experimental advantages, such as their external development and optical clarity, which allow for high resolution imaging of physiological processes in neurons.

Of special interest to our lab is the involvement of the cellular prion protein (PrPC) as a common receptor for various neurotoxic species in the brain, including amyloid β (aβ), α-synuclein and its own misfolded isoform, PrPSc. This intriguing role of PrPC as a broad transducer of neurotoxicity relies on its physiological ability to elicit complex intracellular signals. Therefore, many of our efforts are aimed at analyzing how PrP modulates molecular pathways and cellular events in health and disease.

Currently, our projects center around the following topics:

-The complex roles of PrPC- and SFK-associated pathways during early morphogenesis and neural development, their genetic redundancy and compensatory mechanisms, maternal and zygotic gene functions.
-Neurotoxic pathways induced by amyloids in vivo and their connection to the PrPC/SFK-mediated control of neuroreceptor and adhesion molecule activity.
-Spatiotemporal dynamics of amyloid aggregation in the nervous system, their cellular uptake and processing.
-Development of embryo-based neurotoxicity reporter assays to screen for anti-neurodegeneration drugs.

Kushawah, G., Hernandez-Huertas, L., Abugattas-Nuñez Del Prado, J., Martinez-Morales, J.R., DeVore, M.L., Hassan, H., Moreno-Sanchez, I., Tomas-Gallardo, L., Diaz-Moscoso, A., Monges, D.E., Guelfo, J.R., Theune, W.C., Brannan, E.O., Wang, W., Corbin, T.J., Moran, A.M., Sánchez Alvarado, A., Málaga-Trillo, E., Takacs, C.M., Bazzini, A.A., Moreno-Mateos, M.A. (2020) CRISPR-Cas13d Induces Efficient mRNA Knockdown in Animal Embryos. Developmental Cell. 54(6):805-817.e7
Málaga-Trillo, E., Ochs, K. (2016) Uncontrolled SFK-mediated protein trafficking in prion and Alzheimer's disease. Prion. 10(5):352-361
Sempou, E., Biasini, E., Pinzón-Olejua, A., Harris, D.A., Málaga-Trillo, E. (2016) Activation of zebrafish Src family kinases by the prion protein is an amyloid-β-sensitive signal that prevents the endocytosis and degradation of E-cadherin/β-catenin complexes in vivo. Molecular neurodegeneration. 11:18
Ochs, K., Málaga-Trillo, E. (2014) Common themes in PrP signaling: the Src remains the same. Frontiers in cell and developmental biology. 2:63
Pinzón-Olejua, A., Welte, C., Abdesselem, H., Málaga-Trillo, E., Stuermer, C.A. (2014) Essential roles of zebrafish rtn4/Nogo paralogues in embryonic development. Neural Development. 9:8
Solis, G.P., Radon, Y., Sempou, E., Jechow, K., Stuermer, C.A., and Málaga-Trillo, E. (2013) Conserved roles of the prion protein domains on subcellular localization and cell-cell adhesion. PLoS One. 8(7):e70327
Málaga-Trillo, E., and Sempou, E. (2009) PrPs: Proteins with a purpose: Lessons from the zebrafish. Prion. 3(3):129-133
Munderloh, C., Solis, G.P., Bodrikov, V., Jaeger, F.A., Wiechers, M., Málaga-Trillo, E., and Stuermer, C.A. (2009) Reggies/flotillins regulate retinal axon regeneration in the zebrafish optic nerve and differentiation of hippocampal and N2a neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience. 29(20):6607-6615
Málaga-Trillo, E., Solis, G.P., Schrock, Y., Geiss, C., Luncz, L., Thomanetz, V., and Stuermer, C.A. (2009) Regulation of Embryonic Cell Adhesion by the Prion Protein. PLoS Biology. 7(3):e55
Rivera-Milla, E., Oidtmann, B., Panagiotidis, C.H., Baier, M., Sklaviadis, T., Hoffmann, R., Zhou, Y., Solis, G.P., Stuermer, C.A., and Malaga-Trillo, E. (2006) Disparate evolution of prion protein domains and the distinct origin of Doppel- and prion-related loci revealed by fish-to-mammal comparisons. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 20(2):317-319
von Philipsborn, A.C., Ferrer-Vaquer, A., Rivera-Milla, E., Stuermer, C.A., and Málaga-Trillo, E. (2005) Restricted expression of reggie genes and proteins during early zebrafish development. The Journal of comparative neurology. 482(3):257-272
Reuter, A., Málaga-Trillo, E., Binkle, U., Rivera-Milla, E., Beltre, R., Zhou, Y., Bastmeyer, M., and Stuermer, C.A.O. (2004) Evolutionary Analysis and Expression of Teleost Thy-1. Zebrafish. 1(3):191-201
Málaga-Trillo, E., Laessing, U., Lang, D.M., Meyer, A., and Stürmer, C.A.O. (2002) Evolution of duplicated reggie genes in zebrafish and goldfish. Journal of molecular evolution. 54(2):235-245
Málaga-Trillo, E. and Meyer, A. (2001) Genome duplications and accelerated evolution of Hox genes and cluster architecture in teleost fishes. American zoologist. 41(3):676-686
Meyer, A. and Málaga-Trillo, E. (1999) More fishy tales about hox genes. Current biology : CB. 9(6):R210-213