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

  • Ana Martín

Rational and precise targeting of oncogene-driven signalling is a crucial and yet today outstanding challenge in current 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 posttranslational modifications and allosteric inputs, and how they assemble into macromolecular protein complexes to transmit signals inside the cell. We place 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 more potent and specific protein kinase inhibitors, leading eventually to more effective drugs for the treatment of cancer patients.

We apply an integrated and multidisciplinary approach 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-visualization 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 the design, development, and optimization of protein kinase inhibitors as therapeutic agents in cancer.

Publicaciones

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  • 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
  • Cuesta N, Contreras MJ, Sanchez-Waldermer J, Soriano-Maldonado P, Martin-Hurtado A, Munoz IG, Llimargas M, Munoz J, Plaza- Menacho I (2022). An allosteric switch between the activation loop and a c-terminal palindromic phospho-motif controls c-Src function. BioRivx (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.
  • Plaza-Menacho I (2018). Structure and function of RET in multiple endocrine neoplasia type 2. Endocr-Relat Cancer 25, T79-T90. Publicación CNIO.
  • Radaelli S, Plaza-Menacho I, Mologni L (2018). Novel targeted Therapeutics for MEN2. Endocr-Relat Cancer 25, T53-T68. Publicación CNIO.

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