Aims
The aims of this « Lung diseases » WP are to:
- Advance research and patient care in the 3 main age-related pulmonary diseases: COPD, pulmonary fibrosis and lung cancer.
- Tackle inflammatory, fibro proliferative, cancerous and genetic lung diseases by developing novel approaches in system biology and integrative biology, and providing new investigational and therapeutic tools.
Leader name(s)
Pr. CH. Marquette
Dr P. Saintigny
Pr. P. Hofman
Dr B. Mari
General description
Age related chronic pulmonary diseases and cancer share immune, inflammatory, and metabolic abnormalities associated with conditions inducing cellular senescence, including oxidative stress, genomic instability, DNA damage, dysfunction of mitochondria and telomeres.
Novel exciting perspectives have been provided in lung biology by recent breakthroughs: the complex interplays between intrinsic or alien cellular components can influence strongly the normal function of lung tissue.
The reinforcement of on-going programs on inflammatory, fibro-proliferative, cancerous and genetic lung diseases, combined with development of novel technologies in cell biology (3D cultures, stem cells, genome editing, metagenomics, genetics, functional genomics, and pharmacology) will open major breakthroughs in lung diseases. Many unknowns remain in the description and understanding of the mechanisms at work during normal tissue differentiation, or in adverse situation experienced during ageing or cancer. A major aim of this WP will be to translate novel concepts in better medical practice.
Organization of Oncoage allows the sharing in a single site of large clinical and analytical data and their matched bio banking products in the field of COPD, pulmonary fibrosis and lung cancer. Dissemination of the Oncoage results, through publications of high impact publications, organization of international training programs, development of the intellectual property and involvement in a large number of clinical trials will result from this new organization.
- Task Title
- Epithelium in respiratory diseases
- Task Description
Understanding how alterations in the airway epithelium, considered as a unique barrier against pollutants, aeroallergens or microbes, can contribute to occurrence of several respiratory diseases (cystic fibrosis, asthma, fibrosis, cancer).
Our particular emphasis is on the roles played by non-coding RNAs (especially microRNAs and lncRNAs). We develop our research on 3D cultures of airway cells, which are possibly bioengineered (by transfection, transduction, editing, pharmacological treatments…), then investigated by a combination of functional measurements and high dimensional “omics” approaches (RNAseq, ChIPseq, proteomics).
We are interested by the cellular responses to environmental stresses as well as by the identification of specific subpopulations of cells (by single-cell approaches).
- Task Improvement
- Finding new epithelial therapeutic targets.
- Preventing decrease in lung respiratory function.
- Reachable in 5 years
- Task Title
- COPD
- Task Description
Developing new therapeutic approaches to interfere with altered lung mechanics in pulmonary emphysema.
Understand anti-elastase protection mechanisms may be functionally impaired.
Understand the relationship between COPD lung cancer development
- Task Improvement
- Preventing decrease in pulmonary function.
- Improving exercise capacity
- Improving early stage lung cancer detection rate.
- Reachable in 3 years
- Task Title
- Pulmonary fibrosis
- Task Description
Helping unravel the complex physiopathology of fibro proliferative disorders. Understanding the maintenance of the aggressive phenotype of fibroblasts (myo-fibroblasts) and trying to reverse it.
Identifying new therapeutic targets and new potential pharmacological agents. Preclinical assessing on murine models of pulmonary fibrosis.
Identify non-invasive biomarkers for diagnosis and prognosis.
- Task Improvement
- Identifying new therapeutic targets and agents in lung fibrosis.
- Slower the decline of respiratory function.
- Predict the disease outcome in order to offer an individualized management (personalized medicine).
- Reachable in 2 years
- Task Title
- Transition through ages
- Task Description
Improving the transitions between paediatric and adult medical care of chronic lung diseases such as cystic fibrosis and asthma.
- Task Improvement
- Reducing impact of age on medical care.
- Reachable in 1 years
- Task Title
- Lung cancer
- Task Description
Developing new biomarkers from liquid biopsies for screening, diagnosis, prognosis and theragnosis of lung cancer (circulating tumour cells, miRNA and free circulating DNA) in collaboration with industrial partners (Roche Institute, AstraZeneca, Novartis, Boerhinger, Sanofi, Genentech).
Identifying ncRNAs associated with the aggressiveness of early-stage lung tumours, in particular in response to hypoxia, a predictor of worse survival in lung cancer patients
Developing new approaches (direct and indirect methods) for biomarkers assessment in tight collaboration with private diagnostic company partners (Life technology, Biocartis, RareCells and Johnson & Johnson).
- Task Improvement
- Improving lung cancer patient’s survival.
- Identifying new therapeutic targets
- Improving prediction of disease outcome for early stages
- Reachable in 4 years