2019-Present: Ramon and Cajal Researcher at Centro de Investigación del Cáncer and Departamento de Biología y Bioquímica Molecular, University of Salamanca (Spain).
2018-2019: Lecturer at Departamento de Biología y Bioquímica Molecular, University of Salamanca (Spain).
2013-2018: Lecturer at Barts Cancer Institute in the Center for Cancer and Inflammation (Queen Mary University of London, United Kingdom).
2007-20013: Post-doctoral Research Fellow with Professor Julian Downward at the Cancer Research UK London Research Institute working on the role of Ras and PI3-kinase in tumour maintenance and motility (London, United Kingdom).
2001-2007: MSc and PhD in Microbiology with Profesor Eugenio Santos at Centro de Investigacion del Cancer working on the specificity of the different Ras Isoforms (Salamanca, Spain).
1995-2000: BSc in biochemistry at the University of Salamanca (Spain).
Centro de Investigación del Cáncer (Universidad de Salamanca-CSIC)
Campus Universitario Miguel de Unamuno s/n
Areas of Research
Our lab aims to understand how oncogenic Ras proteins drive cancer development by regulating the interplay between tumour cells and its microenvironment in lung cancer. Interactions between tumoral cells and the surrounding stroma are essential to maintain tumour growth and cancer progression. These interactions provide proliferative and migratory advantages that help tumour development.
Ras oncogenes are key players in the initiation and development of cancer. We have shown that Ras signalling through PI3-Kinase is essential for tumour maintenance and also for cell motility. However little is known about how Ras signalling can modulate the stroma to support tumour progression. Initially we will aim to investigate how Ras-PI3-Kinase signalling in the stroma might contribute to the establishment and progression of cancer and how this signalling influences the tumor-stroma relationship.
The specific points that my research aims to address are:
1. What is the role of oncogenic Ras in the establishment and function of different stromal components?
By disrupting Ras signalling in different stromal components or in the tumour cells we aim to uncover how it contributes to the establishment of the different components of a functional stroma (cytokine production, growth factor secretion and/or metabolic symbiosis).
2. What is the role of Ras signalling in tumour-stroma co-evolution?
We have preliminary data showing that Ras-PI3-Kinase signalling has a role in the dependency of the tumour on its stroma. By disrupting Ras signalling at different stages of tumour development we aim to unveil what are the different signalling pathways and molecular interactions that are essential for tumour progression.
3. How does different tumour drivers modulate stroma composition and function?
Different mutations can lead to the same type of tumour. A good example is K-Ras and EGFR mutations in lung cancer. We will investigate how stroma function and composition depends on the mutations present in the tumoral cells. Specific targeting of signalling pathways in the cancer-associated stromal microenvironment alone or in combination with known conventional therapeutic modalities could have a synergistic effect on cancer treatment thus provide a better treatment to patients and increase survival.
Identifying the key molecules required for RAS-dependent tumour-stroma crosstalk is fundamental to better understand the biology of RAS-driven lung cancer. This will lay the foundation for developing new treatments focused on modulating host responses in order to alter the functionality of cancer cells and sensitize them to additional therapies.
(*) Means equal contribution as senior authors.
Mendoza P, Martínez-Martín N, Bovolenta ER, Reyes-Garau D, Hernansanz-Agustín P, Delgado P, Diaz-Muñoz MD, Oeste CL, Fernández-Pisonero I, Castellano E, Martínez-Ruiz A, Alonso-López D, Santos E, Bustelo XR, Kurosaki T, Alarcón B,
Sci Signal; 2018; 11(532); eaal1506; 29844052
Krygowska AA, Castellano E,
Cold Spring Harb Perspect; 2018; 8(6); a031450; 28847905
Castellano E, Molina-Arcas M, Krygowska AA, East P, Warne P, Nicol A, Downward J,
Nat Commun; 2016; 7(); 11245; 27071537
Godin-Heymann N, Brabetz S, Murillo MM, Saponaro M, Santos CR, Lobley A, East P, Chakravarty P, Matthews N, Kelly G, Jordan S, Castellano E, Downward J,
Oncogene; 2016; 35(25); 3324-34; 26455320
Murillo MM, Zelenay S, Nye E, Castellano E, Lassailly F, Stamp G, Downward J,
J. Clin. Invest.; 2014; 124(8); 3601-11; 25003191
Castellano E, Sheridan C, Thin MZ, Nye E, Spencer-Dene B, Diefenbacher ME, Moore C, Kumar MS, Murillo MM, Grönroos E, Lassailly F, Stamp G, Downward J,
Cancer Cell; 2013; 24(5); 617-30; 24229709
Castellano E, Downward J,
Genes Cancer; 2011; 2(3); 261-74; 21779497
Castellano E, Santos E,
Genes Cancer; 2011; 2(3); 216-31; 21779495
Iborra S, Soto M, Stark-Aroeira L, Castellano E, Alarcón B, Alonso C, Santos E, Fernández-Malavé E,
Blood; 2011; 117(19); 5102-11; 21444916
Castellano E, Downward J,
Curr. Top. Microbiol. Imm; 2010; 346(); 143-69; 20563706
Drosten M, Dhawahir A, Sum EY, Urosevic J, Lechuga CG, Esteban LM, Castellano E, Guerra C, Santos E, Barbacid M,
EMBO J.; 2010; 29(6); 1091-104; 20150892
Castellano E, Guerrero C, Núñez A, De Las Rivas J, Santos E,
Genome Biol.; 2009; 10(11); R123; 19895680
Castellano E, De Las Rivas J, Guerrero C, Santos E,
Oncogene; 2007; 26(6); 917-33; 16909116
Gutiérrez-Berzal J, Castellano E, Martín-Encabo S, Gutierrez-Cianca N, Hernández JM, Santos E, Guerrero C,
Exp. Cell Res.; 2006; 312(6); 938-48; 16443220