skip to primary navigationskip to content
 

Carla Martins

cm sm

Dr Carla Martins

Biography | Pubmed

Modelling Tumour Development and Therapy

 

 

Schematic representation of research strategy

Schematic representation of research strategyThe main aim of our programme is to define the molecular and functional alterations that enable lung tumour progression from benign stages to high-grade adenocarcinoma. While our immediate goal is to improve the targeting of tumours harbouring particular sets of mutations, our ultimate goal is to identify broader and targetable signatures associated with benign and advanced disease. We are currently focused on the evolution of lung tumours expressing mutant versions of Kras and p53.  


Despite being two of the most frequent mutations in human lung adenocarcinoma, how each of these key alterations contributes to malignant progression remains unclear. To address these key questions our lab uses a multidisciplinary approach that combines the generation of genetically modified tumour models that closely
recapitulate the evolution of the human disease to “omics” approaches, microscopy and in-vivo imaging.

Our Main Research Themes Are:

cpm2.jpg
Understanding the mechanisms of lung tumour evolution in vivo: KrasG12D-driven lung tumour showing up-regulation of p19 ARF during low-to-high grade transition (from Junttila, et al. (2010) Nature 468, 567-571).
Role and prognostic implications of Kras locus alterations on lung tumour progression 

We previously identified Kras allelic imbalance as a frequent alteration associated with advanced murine lung tumours and these genetic changes are also frequently encountered in human lung cancer. Using a multidisciplinary approach we aim to establish the prognostic and therapeutic implications of these alterations.

Impact of p53 mutations on lung cancer progression and therapy
p53 mutations affect almost half of all human cancers and are among the few mutational events associated with lung cancer malignant progression. The oncogenic and therapeutic impact of these mutations in lung cancer remains largely unknown. Using mouse models that closely recapitulate the human disease we aim to define the oncogenic effect of p53 mutations on lung cancer progression and therapy.

Molecular and functional requirements of lung cancer evolution
Using unbiased genetic, transcriptional and metabolic approaches we aim to dissect the mechanistic drivers of lung tumour evolution in order to identify targetable signatures associated with benign and advanced disease.

 

 


 

Selected Publications:

Lung tumors with distinct p53 mutations respond similarly to p53-targeted therapy but exhibit genotype-specific statin sensitivity. Turrell FK, Kerr EM, Gao M, Thorpe H, Doherty G, Cridge J, Shorthouse D, Speed A, Samarajiwa S, Hall BA, Meryl Griffiths M and Martins CP. Genes and Development (in press)

KRAS Allelic Imbalance: Strengths and Weaknesses in Numbers. Doherty GJ, Kerr EM, Martins CP. Trends Mol Med. 2017 May;23(5):377-378. doi: 10.1016/j.molmed.2017.03.005. Epub 2017 Mar 31. PMID: 28372922.

Metabolic rewiring in mutant Kras lung cancer. Kerr EM, Martins CP. FEBS J. 2017 Jun 1. doi: 10.1111/febs.14125. [Epub ahead of print] Review.

Mutant Kras copy number defines metabolic reprogramming and therapeutic susceptibilities. Kerr E, Guade E, Turrell F, Frezza C, Martins CP. Nature. 2016 March 03; (531):110–113; doi:10.1038/nature16967; Epub 2016 Feb 24.

From tumor prevention to therapy: Empowering p53 to fight back. Frezza C, Martins CP. Drug Resist Updat. 2012 Oct;15(5-6):258-67. doi: 10.1016/j.drup.2012.10.001.

Validation of MdmX as a therapeutic target for re-activating p53 in tumors. Garcia D, Warr MR, Martins CP, Brown Swigart L, Passegué E, Evan GI. Genes & Development.Genes Dev. 2011 Aug 15;25(16):1746-57. doi: 10.1101/gad.16722111.

Selective activation of p53-mediated tumour suppression in high-grade tumours.Junttila MR, Karnezis AN, Garcia D, Madriles F, Kortlever RM, Rostker F, Brown Swigart L, Pham DM, Seo Y, Evan GI, Martins CP. Nature. 2010 Nov 25;468(7323):567-71.

Modeling the therapeutic efficacy of p53 restoration in tumors. Martins CP, Brown-Swigart L, Evan GI. Cell. 2006 Dec 29;127(7):1323-34.


 

Contact:

Click here to contact Dr Carla Martins by email.