Grupo de Quinasas, Fosforilación de Proteínas y Cáncer

Inicio | Investigación e innovación | Programas Científicos | Programa de Biología Estructural | Grupo de Quinasas, Fosforilación de Proteínas y Cáncer

Ivan Plaza Menacho

Becarios Post-doctorales

  • Julia María Contreras

Becarios Pre-Doctorales

  • Saray Aragón

Rational and precise targeting of oncogene-driven signalling is a crucial and yet today outstanding challenge in cancer research. Understanding the structural and molecular bases of oncogene activation and signalling is key for the design and development of better therapeutics. Our research focuses on the structural and molecular understanding of protein kinase function: how protein kinases are activated and regulated by post-translational modifications and allosteric inputs, and how they assemble into macromolecular protein complexes to transmit signals inside the cell. We put a special emphasis on how these mechanisms are corrupted in cancer due to oncogenic mutations and other oncogenic insults. Crucially, such atomic and molecular information can be translated into the design and development of next generation protein kinase inhibitors for targeted and personalised therapies.

We apply an integrated and multidisciplinary approach by combining: molecular biology for the generation of suitable constructs; protein biochemistry and biophysics for protein purification, quality assessment and functional evaluation; mass spectrometry (MS) for the identification and quantification of post-translational modifications; X-ray crystallography for the 3D-visualisation of proteins; and Drosophila as an in vivo model for data validation. Furthermore, we use structure-guided drug discovery and MD simulation approaches to exploit structural and functional vulnerabilities for drug design and development.

Publicaciones

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  • Lucena-Agell D, Guillen MJ, Matesanz R, Alvarez-Bernad B, Hortiguela R, Avilés P, Martínez-Díez M, Santamaría-Nuñez G, Contreras J, Plaza-Menacho I, Giménez-Abián J, Oliva MCC, Díaz J (2024). PM534, an optimized target protein interaction strategy through the colchicine site of tubulin. J Med Chem (in press). Publicación en otras instituciones.
  • Cuesta N, Contreras MJ, Sanchez-Waldermer J, Soriano-Maldonado P, Martin-Hurtado A, Munoz IG, Llimargas M, Munoz J, Plaza- Menacho I (2023). An allosteric switch between the activation loop and a c-terminal palindromic phospho-motif controls c-Src function. Nat Commun 14, 6548. Publicación CNIO. Open Access Open Access
  • Shehata MA, Contreras J, Martín-Hurtado A, Froux A, Mohamed HT, El-Sherif AA, Plaza-Menacho I (2022). Structural and dynamic determinants for highly selective RET kinase inhibition reveal cryptic druggability. J Advanced Res (in press). Publicación CNIO. Open Access Open Access
  • Dubey BN, Agustoni E , Böhm R , Kaczmarczyk A , Mangia F, von Arx C, Jenal U , Hiller S, Plaza-Menacho I,Schirmer T (2020). Hybrid Histidine Kinase Activation by Cyclic di-GMP-mediated Domain Liberation.. Proc Natl Acad Sci USA 117, 1000-1008. Publicación en otras instituciones.

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