Dr Esther Castellano-Sanchez

Dr Esther Castellano-Sanchez

BSc, PhD
Centre: Cancer and Inflammation
Early Career Researcher - Lecturer
This email address is being protected from spambots. You need JavaScript enabled to view it.

QMUL Directory


My work is on the role of oncogenic Ras signalling in cancer development and the interplay between tumour cells and the microenvironment in lung and pancreatic cancer.

 

Research Details

The main goal of my research is to understand the role of oncogenic Ras signalling in cancer development and in the interplay between tumour cells and its microenvironment in lung and pancreatic cancer.

The interaction between tumour and surrounding stromal cells is essential to maintain tumour growth and cancer progression. Different stroma cell types contribute to tumour growth by facilitating apoptosis resistance, creating a niche for cancer stem cells, enabling immune escape of tumour cells, modulating angiogenesis, facilitating metastatic spread or increasing therapy resistance.

The Ras oncogenes are key players in the initiation and development of cancer. During my postdoctoral work I have shown that Ras signalling through PI3-Kinase is essential for tumour maintenance and also for cell motility. However little is known about how these oncogenes can modulate the stroma to support tumour progression and my aim is to investigate how Ras-PI3-Kinase signalling in the stroma contributes to the establishment and progression of cancer

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 the stroma 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, signalling and/or metabolic symbiosis).

We also aim to understand how Ras-PI3Kinase signaling in the tumour-associated macrophages (TAMs) affects tumour growth or response to different cancer drugs.

2. What is the role of Ras signalling in tumour-stroma co-evolution?

We have preliminary data showing that Ras-PI3-Kinase signalling influences the dependency of the tumour on its stroma. We aim to understand how this pathway influences different aspects of stroma biology during tumour development by analysing the effect of disrupting Ras-PI3-Kinase signalling at different stages. Understanding how the tumour stroma evolves will give us an insight on how and when it should be targeted to achieve a better response to cancer drugs.

3. How do different tumour drivers modulate stroma composition and function?

Different mutations can lead to the development of tumour that are similar in their clinical and histological properties, one example being that both mutations in K-Ras and EGFR are drivers of non-small cell lung cancer. We aim to investigate how these two different tumour drivers affect stroma composition and function, namely cytokine production, growth factor secretion and tumour-stroma signalling.

Profile

  • 2013: Early Career Researcher-Lecturer at Barts Cancer Institute in the Center for Cancer and Inflammation.
  • 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.
  • 2001-2007: MSc and PhD in Microbiology with Professor Eugenio Santos at Centro de Investigacion del Cancer (Salamanca, Spain) working on the specificity of the different Ras Isoforms.
  • 1995-2000: BSc in biochemistry at the University of Salamanca (Spain) in 2000.

Funding

  • Early Career Researcher Fellowship, Barts Cancer Institute

Key Publications

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. Requirement for interaction of PI3-kinase p110α with RAS in lung tumor maintenance. Cancer Cell. 2013 Nov 11;24(5):617-30. PMID: 24229709

Iborra S, Soto M, Stark-Aroeira L, Castellano E, Alarcón B, Alonso C, Santos E, Fernández-Malavé E. H-ras and N-ras are dispensable for T-cell development and activation but critical for protective Th1 immunity. Blood. 2011 May 12;117(19):5102-11. PMID: 21444916

Castellano E, Guerrero C, Núñez A, De Las Rivas J, Santos E. Serum-dependent transcriptional networks identify distinct functional roles for H-Ras and N-Ras during initial stages of the cell cycle. Genome Biol. 2009;10(11):R123. PMID: 19895680

Castellano E, De Las Rivas J, Guerrero C, Santos E. Transcriptional networks of knockout cell lines identify functional specificities of H-Ras and N-Ras: significant involvement of N-Ras in biotic and defense responses. Oncogene. 2007 Feb 8;26(6):917-33. PMID: 16909116


Further Publications

Additional publications will be available here.


My work is on the role of oncogenic Ras signalling in cancer development and the interplay between tumour cells and the microenvironment in lung and pancreatic cancer.

 

External Activities

Member of the Spanish Society of Biochemistry and Molecular Biology (FEBS membership)

This site uses cookies in order to function properly. By continuing to browse, you agree that we can save them on your device. Privacy Policy.