Characterisation of the endocannabinoid system and its possible therapeutic use for interstitial lung pathologies

The  team focuses on studying the cannabinoid system in pulmonary fibrosis. They intend to study the possible use of a CB1 receptor signaling to treat fibrosis. Their preliminary data show an increase in the expression of the receptor and its endogenous ligand -2-arachidonylglycerol (2-AG)- in the plasma of animals with fibrosis and in patients with idiopathic pulmonary fibrosis. The CB1 receptor is highly expressed in fibroblasts and regulates cell proliferation; therefore, they hypothesize that a CB1 antagonist could reduce fibroproliferation, a potential therapy for treating pulmonary fibrosis.

Identification of immune markers associated to the progression and response to antifibrotic treatments of pulmonary fibrosis patients

Interstitial and intraalveolar fibrosis are characteristics of the more advanced stages of acute respiratory syndrome (for example, post-COVID-19 infection), fibrosing interstitial pathologies, and other lung pathologies. These pathologies are characterised by the abnormal and excessive deposition of extracellular matrix proteins, mainly collagen. Histologically and biochemically, all of these entities are similar, and it is still not known why some patients develop fibrosis and others do not. The group studies the mediators and cellular events that occur in these disorders, which lead to the development of progressive pulmonary fibrosis. They focus on the study of the immune response and how it is capable, or not, of controlling the correct regeneration of the lung alveoli or their incorrect repair with the uncontrolled proliferation of fibroblasts.

Innate and adaptive immune response in front of infections, focusing on how certain comorbidities, such as diet-associated obesity, impact the immune response

GPR55 has been described by the group as playing a key role in regulating the adaptive immune response. This receptor is also highly expressed in neutrophils, which are crucial cells during the first stages of acute lung injury. The group hypothesises that impaired GPR55 signaling affects neutrophil function by enhancing their radical oxygen species production and triggering NETosis. In addition, it is well known that our daily diet impacts our immune system and vulnerability to disease. Diet-associated obesity is associated with metabolic, cardiovascular diseases, and other non-communicable diseases, such as many respiratory diseases. The group hypothesises that unbalanced daily nutrition triggers myeloid cell production, promoting overstimulation of the immune system and leading to an overwhelmed response in front of respiratory diseases. They propose an omics-driven approach combined with phenotypic and functional assays to enlighten the links between daily diet, hematopoiesis, myeloid cell maturation, immune system homeostasis & systemic inflammation, and its impact on lung pathologies.

Description of the genetic and molecular profiles of lung cancer in patients with chronic lung pathologies

This research line includes mutational screening, using next-generation sequencing techniques (whole exome sequencing), of tumours obtained from patients suffering from lung cancer and comparing them to that of lung cancer patients and patients with a previous chronic respiratory disease. The group is interested in determining how the parenchymal lung alterations affect patients who develop lung cancer. The team will also study differential epigenetic markers between "healthy" lung cancer patients and patients with lung cancer and previous chronic lung pathology. At the moment, they are studying the effect of interstitial pathologies - pulmonary fibrosis - on lung cancer tumour growth. This will allow them to identify new therapeutic targets and the possible alterations responsible for acquired resistance to new treatments.

Functional analysis in 3D models of the genes altered in the lung tumours of patients with previous interstitial pathology

The group aims to mimic the conditions and interactions between tumour cells and lung resident cells (alveolar macrophages, fibroblasts, and alveolar, and endothelial cells), and do so under profibrotic and "normal" conditions. This will allow them to study the response of tumour cells and changes in proliferation and functionality. Furthermore, these complex 3D models will allow them to study the response of tumour cells and their changes in proliferation and functionality, simulating a healthy lung or one with pulmonary fibrosis and a tumour; these models will allow them to test drugs or other therapies to determine the response of the tumoral cells.

Role of cannabinoid system in lung fibrosis

PI: Raquel Guillamat-Prats
Funding agency: Instituto de Salud Carlos III (ISCIII)
Agency code: CP20/00133
Duration: 01/03/2021 - 28/02/2026

Nueva diana terapéutica para la fibrosis pulmonar: señalización vía el eje CB1/2-AG en las células alveolares y los fibroblastos pulmonares

PI: Raquel Guillamat-Prats
Funding agency: Instituto de Salud Carlos III (ISCIII)
Agency code: PI23/00460
Duration: 01/01/2024 - 31/12/2026

Papel de los receptores canabinoides en la fibrosis pulmonar

PI: Raquel Guillamat-Prats
Funding agency: AGAUR
Agency code: INVESTIGO Contract
Duration: 01/10/2022 - 30/09/2024

Role of cannabinoid system in lung fibrosis

PI: Raquel Guillamat-Prats
Funding agency: Societat Catalana de Pneumologia (SOCAP)
Agency code: SOCAP Emergent 2022
Duration: 01/04/2022 - 30/03/2024

Deciphering the role of macrophages in lung cancer and pulmonary fibrosis

PI: Raquel Guillamat-Prats
Funding agency: Hospital Germans Trias i Pujol
Agency code: Talents fellowship for an Undergraduate Student.
Duration: 01/10/2022-30/09/2024