Joaquín Castilla
Joaquín Castilla
PRINCIPAL INVESTIGATOR
Ikerbasque Research Professor
Prion Research Lab
Address: Bizkaia Science and Technology Park, building 502, Derio (Bizkaia)

Dr. Joaquín Castilla is a Ikerbasque Research Professor incorporated at CIC bioGUNE in 2009. He has a long experience working in prions since 1998 at Center for Animal Health (CISA -INIA). In 2003, he moved to Switzerland to work as Research Scientist at Serono Research Institute. He became Assistant Professor this year, first at the University of Texas, Medical Branch and later at Scripps (Florida) from 2006 leading an independent group. His expertise is based on in vitro and in vivo replication of prions. Particularly, his group is studying the strain and species barrier phenomena in a cell-free system, trying to dissect the molecular mechanisms by which prions propagate and focusing on new anti-prion therapeutic approaches.
The most important achievements of his group are: i) development of the most sensitive method for prion detection, ii) generation of prion infectivity in a test tube contributing to validate the “protein-only” hypothesis. Iii) prion detection in blood for the first time in pre-symptomatic and symptomatic animals and iv) confirmation that the in vitro prion propagation faithfully mimicked the three major phenomena governing transmissible spongiform diseases: infectivity, strain concept and transmission barrier.

Dr. Joaquín Castilla has extensive experience in European Community, NIH (USA) and other national projects. His group has over 20 active collaborations both in Europe and outside the European Union with the most prestigious groups in the prion field. He is a member of the Journal Veterinary Research editorial board and review for dozens of international journals as The EMBO J., Neuron, Nature, among others. He has supervised 8 doctoral theses and currently leads/co-leads another 4 thesis in preparation.

Dr Castilla has published more than 75 peer reviewed articles (H index: 32 – Times cited: 3162 – Cumulative Impact Factor: ~595) which many of them have been instrumental for understanding the molecular mechanisms for prion propagation.

Lastest Publications

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Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative disorders affecting both humans and animals. TSEs can be of genetic, sporadic or infectious origin. The infectious agent associated with TSEs, termed prion, appears to consist of a single protein, an abnormal conformer (PrPSc) of a natural host protein (PrPC), which propagates by converting host PrPC into a replica of itself. One of the characteristics of prions is their ability to infect some species and not others. This phenomenon is known as transmission barrier. Interestingly, prions occur in the form of different strains that show distinct biological and physicochemical properties, even though they are encoded by PrP with the same amino acid sequence, albeit in presumably different conformations. In general, the transmission barrier is expressed by an incomplete attack rate and long incubation times (time from the animal inoculation until the onset of the clinical signs) which become shorter after serial inoculation passages. Compelling evidence indicates that the transmission barriers are closely related to differences in PrP amino acid sequences between the donor and recipients of infection, as well as the prion strain conformation. Unfortunately, the molecular basis of the transmission barrier phenomenon and its relationship to prion strain conformations is currently unknown and we cannot predict the degree of a species barrier simply by comparing the prion proteins from two species.

We have conducted a series of experiments using the Protein Misfolding Cyclic Amplification (PMCA) technique that mimics in vitro some of the fundamental steps involved in prion replication in vivo, albeit with accelerated kinetics. The in vitro generated prions possess key prion features, i.e., they are infectious in vivo and maintain their strain specificity. We have used PMCA to efficiently replicate a variety of prion strains from, among others, mice, hamsters, bank voles, deer, cattle, sheep, and humans. The correlation between in vivo data and our in vitro results suggest that PMCA is a valuable tool for assessing the strength of the transmission barriers between diverse species and for different prion strains; we are using the method to determine which amino acids in the PrPC sequence contribute to the strength of the transmission barrier. These studies are proving very useful in evaluating the potential risks to humans and animals, of not only established prion strains, but also new (atypical) strains. For example, while classical sheep scrapie is unable to cross the human transmission barrier in vitro, bovine spongiform encephalopathy (BSE) propagated in sheep does so efficiently. In addition, we have also generated prions that are infectious to species hitherto considered to be resistant to prion disease.

http://www.asociacioncjd.org/

Lastest Publications

Development of a new largely scalable in vitro prion propagation method for the production of infectious recombinant prions for high resolution structural studies

Erana, H;Charco, JM;Di Bari, MA;Diaz-Dominguez, CM;Lopez-Moreno, R;Vidal, E;Gonzalez-Miranda, E;Perez-Castro, MA;Garcia-Martinez, S;Bravo, S;Fernandez-Borges, N;Geijo, M;D'Agostino, C;Garrido, ...

PLOS PATHOGENS

2019-10-01

Qualitative analysis of the social and family impact of human transmissible spongiform encephalopathies

Coca, JR;Sanz-Molina, L;Erana, H;Castilla, J

REVISTA DE NEUROLOGIA

2019-09-16

A Single Amino Acid Substitution, Found in Mammals with Low Susceptibility to Prion Diseases, Delays Propagation of Two Prion Strains in Highly Susceptible Transgenic Mouse Models

Otero, A;Hedman, C;Fernandez-Borges, N;Erana, H;Marin, B;Monzon, M;Sanchez-Martin, MA;Nonno, R;Badiola, JJ;Bolea, R;Castilla, J

MOLECULAR NEUROBIOLOGY

2019-09-01

Insights into the Bidirectional Properties of the Sheep-Deer Prion Transmission Barrier

Harrathi, C;Fernandez-Borges, N;Erana, H;Elezgarai, SR;Venegas, V;Charco, JM;Castilla, J

Molecular neurobiology

2019-08-01

The Prion 2018 round tables (II): A beta, tau, alpha-synuclein horizontal ellipsis are they prions, prion-like proteins, or what?

Erana, H

PRION

2019-01-01

Repurposing ciclopirox as a pharmacological chaperone in a model of congenital erythropoietic porphyria

Urquiza, P(Urquiza, Pedro);Lain, A(Lain, Ana);Sanz-Parra, A(Sanz-Parra, Arantza);Moreno, J(Moreno, Jorge);Bernardo-Seisdedos, G(Bernardo-Seisdedos, Ganeko);Dubus, P(Dubus, Pierre);Gonzalez, ...

Science translational medicine

2018-09-19

An Amino Acid Substitution Found in Animals with Low Susceptibility to Prion Diseases Confers a Protective Dominant-Negative Effect in Prion-Infected Transgenic Mice

Otero, A(Otero, Alicia);Bolea, R(Bolea, Rosa);Hedman, C(Hedman, Carlos);Fernandez-Borges, N(Fernandez-Borges, Natalia);Marin, B(Marin, Belen);Lopez-Perez, O(Lopez-Perez, Oscar);Barrio, T(Barrio, ...

Molecular neurobiology

2018-07-01

iPS Cell Cultures from a Gerstmann-Straussler-Scheinker Patient with the Y218N PRNP Mutation Recapitulate tau Pathology

Matamoros-Angles, A(Matamoros-Angles, Andreu);Gayosso, LM(Mayela Gayosso, Lucia);Richaud-Patin, Y(Richaud-Patin, Yvonne);di Domenico, A(di Domenico, Angelique);Vergara, C(Vergara, Cristina);Hervera, ...

Molecular neurobiology

2018-04-01

Detection of amyloid fibrils in Parkinson's disease using plasmonic chirality

Kumar, J(Kumar, Jatish);Erana, H(Erana, Hasier);Lopez-Martinez, E(Lopez-Martinez, Elena);Claes, N(Claes, Nathalie);Martin, VF(Martin, Victor F.);Solis, DM(Solis, Diego M.);Bals, S(Bals, Sara);Cortajarena, ...

Proceedings of the National Academy of Sciences of the United States of America

2018-03-27

Cofactors influence the biological properties of infectious recombinant prions

Fernandez-Borges, N(Fernandez-Borges, Natalia);Di Bari, MA(Di Bari, Michele A.);Erana, H(Erana, Hasier);Sanchez-Martin, M(Sanchez-Martin, Manuel);Pirisinu, L(Pirisinu, Laura);Parra, B(Parra, ...

Acta neuropathologica

2018-02-01