- Pablo Soriano
- Hipólito Nicolás Cuesta
Rational and precise targeting of oncogene driven signalling is a crucial and yet outstanding challenge in cancer research today. 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 and disease 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, eventually leading to more effective drugs for the treatment of cancer patients.
- (2018). Structure and function of RET in multiple endocrine neoplasia type 2. Endocr-Relat Cancer 25, T79-T90.
- (2018). Novel targeted Therapeutics for MEN2. Endocr-Relat Cancer 25, T53-T68.
- (2016). RET Functions as a Dual-Specificity Kinase that Requires Allosteric Inputs from Juxtamembrane Elements.. Cell Reports 17, 3319-3332.
- (2016). Cyclic di-GMP mediates a histidine kinase/phosphatase switch by noncovalent domain cross-linking.. Sci Adv 2, e1600823.
- (2014). Oncogenic RET kinase domain mutations perturb the autophosphorylation trajectory by enhancing substrate presentation in trans.. Mol Cell 53, 738-751.
- (2014). Mechanisms of RET signalling in cancer: current and future implications for targeted therapy.. Cell Signal 26, 1743-1752.
- (2013). GDNF-RET signaling in ER-positive breast cancers is a key determinant of response and resistance to aromatase inhibitors.. Cancer Res 73, 3783-3795.
- (2013). Ponatinib is a potent inhibitor of oncogenic RET kinase and overcomes gatekeeper mutant-associated drug resistance.. Mol Cell Endocrinol 377, 1-6.