Translational Lung Cancer Biology

Genomic landscape of LUSC

Observation of the genomic landscape of LUSC has shown that unlike lung adenocarcinoma, which is dominated by alterations in the Ras pathway, there is no single targetable pathway that dominates the genomic landscape of LUSC. Instead, the most frequently altered pathways in LUSC are PI3K/Akt pathway (47%), squamous differentiation pathway (44%) and oxidative stress response (34%).

This figure shows summary of the most relevant tumour suppressors (pink boxes) and pathways (blue boxes) involved in LUSC development, with examples of pathway components altered in LUSC and the percentage of cases with at least one alteration targeting the pathway.

Translational Lung Cancer Biology

New model of LUSC using HBECs

The group intend to unravel the mechanisms that drive the numerous subtypes of LUSC that we observe in patients and the specific vulnerabilities of those subtypes using a new model of LUSC by genetic manipulation on human bronchial epithelial cells (HBECs).

Current methodologies permit efficient expansion of HBECs, genome editing and development of organoids mimicking bronchial morphology. Using these methodologies, we can disentangle how driver alterations induce epithelial perturbations indicative of LUSC initiation and progression. Additionally, HBECs reflect human diversity better than mouse models, constitute a more adequate system to investigate the effect of exposures, mainly smoking, and predisposition.

Figure shows haematoxylin-eosin stained sections or air-liquid interface (ALI) HBEC cultures from wild-type and the mutants HBECs that follow the most likely evolutionary trajectory of LUSC inferred from our results. The diagram below shows the phenotypic changes associated with this evolutionary trajectory.

Lung cancer research graphical representation
Lung squamous cell carcinoma Neighbourhood Analysis

Research areas

Building and interrogating a new human model of lung squamous cell carcinoma

The Translational Lung Cancer Biology laboratory have designed, implemented and characterised a genome engineering strategy. Using genetically modified HBCs, we intend to stablish a proof-of-principle for the use of human bronchial epithelial cells (HBECs) to model LUSC .

Interrogating fibroblasts-cancer cell interactions in lung squamous cell carcinoma

We are interested in understanding how mutant human bronchial epithelial cells behave in vivo and in the presence of pulmonary fibroblasts, in order to enhance the use of our LUSC model for basic and translational research.

Building and interrogating a new human model of lung squamous cell carcinoma
Interrogating fibroblasts-cancer cell interactions in lung squamous cell carcinoma

A note from the Group Leader – Carlos Lopez-Garcia

I am mainly an epithelial biologist interested in understanding what mechanisms determine the transition from a normal epithelium into invasive carcinomas by deconvolving how frequently dysregulated pathways cooperate to alter epithelial homeostasis. I am also interested in finding alternatives to mouse models with two objectives: reducing the use of mice in cancer research and developing models that recapitulate better the human biology.

I am now focusing on lung squamous cell carcinoma to develop my research program. However, I intend to extend my research to other squamous carcinomas, as they are  a group of diseases with similar biological features that are likely to show common vulnerabilities.

Meet the group

Photo of group leader Carlos Lopez-Garcia
Carlos Lopez-Garcia

Institute Fellow

iD
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Anthony Oojageer

Scientific Officer

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