About

The Respiratory and Immune Repair (REPAIR) research group studies the role of the immune system in respiratory health and disease, specifically focusing on alveolar regeneration after an acute or chronic injury. Of particular interest are the function, supply, and production of leukocytes in the lung after disease and the signals that regulate their mobilization after damage such as infection, acute damage or fibrosis.

                                 

The group uses interdisciplinary approaches to study the crosstalk between leukocytes and lung resident cells, such as alveolar type II cells, resident alveolar and interstitial macrophages, and fibroblasts. Its researchers use disease mouse models to mechanistically dissect innate and adaptive immune cell functions in fibrosis and inflammation, as we believe that immune cells are the critical determinant of correct tissue regeneration or impaired reparation. This team further seeks to understand how molecular and cellular signaling through cannabinoid receptors and their lipidic ligands-endogenous cannabinoids-affects acute lung damage and fibrosis progress.

The group has a prior engagement in patient-based research projects in collaboration with pulmonologists, intensivists, surgeons, oncologists and pathologists.

Keywords: Pulmonary fibrosis, acute lung injury, immune system, fibroblasts, macrophages, respiratory diseases.

Lung Immunity Translational Research Group

Group leader

  • Raquel Guillamat Prats, PhD
    Raquel Guillamat Prats, PhD

    Raquel Guillamat Prats, PhD

    As a scientist, Raquel Guillamat has always been interested in tissue regeneration and the crosstalk between immune cells. Her five-year postdoctoral work at IPEK- Ludwig-Maximilians-Universität München was directed at elucidating the role of endocannabinoids in vascular diseases, focusing on how cannabinoid receptors modulate immune cell behavior. Previously, during her PhD (IIBB-CSIC) and first postdoctoral stage (Fundació Parc Taulí), Guillamat studied how to repair the epithelial alveolar layer after acute (acute lung injury) or chronic (pulmonary fibrosis) damage. For instance, she explored the use of cell therapies or anticoagulants to modulate inflammation and cell damage. Currently, the group focuses on understanding the crosstalk between immune and lung stromal cells during homeostasis and diseases, and they work on helping the lungs to regenerate after acute and chronic damages.

    Contact: rguillamat(ELIMINAR)@igtp.cat
    ORCID: 0000-0001-6960-0985

Research lines

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 respiratory diseases, focusing on how certain comorbidities, such as diet-associated obesity, or repetitive infections 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 habits impact our immune system and vulnerability to disease. Many daily habits may impact in our immune system response and in non-communicable diseases, such as many respiratory diseases. The group proposes an omics-driven approach combined with phenotypic and functional assays to enlighten the links between daily diet, repetitive infections, 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.

The group performs functional analysis using cell culture 3D models 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. These models will allow them to test drugs or other therapies to determine the response of the tumoral cells.

Active projects

Endocannabinoid system as novel therapeutic targets in pulmonary fibrosis

PI: Raquel Guillamat-Prats
Funding agency: Instituto de Salud Carlos III (ISCIII)
Agency code: CP20/00133
Duration: 15/03/2021 – 14/03/2026

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

Nueva diana terapéutica para la fibrosis pulmonar idiopática: señalización vía el eje CB1/2-AG en los fibroblastos

PI: Raquel Guillamat Prats
Funding agency: Sociedad Española de Neumología y Cirugía Torácica (SEPAR)
Agency code: Proyecto: 1582
Duration: 01/06/2024 - 31/05/2026

Efectes de les malalties respiratories cròniques en el cancer de pulmó

PI: Raquel Guillamat Prats
Funding agency: AGAUR
Agency code: Doctorat Industrial
Duration: 01/06/2024 – 31/05/2027

Exploring the Therapeutic Potential of GPR55/LPI Axis Modulation in Neutrophils for ARDS Management

PI: Raquel Guillamat Prats
Funding agency: European Society of Intensive Care Medicine (ESICM)
Agency code: 2024 Multidisciplinary Care Award
Duration: 01/10/2024 – 30/09/2026
More information

Past projects

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

El sistema cannabinoide com a nova diana terapèutica per la fibrosi pulmonar

PI: Raquel Guillamat Prats
Funding agency: Societat Catalana de Pneumologia
Agency code: Beca SOCAP INVESTIGADOR EMERGENT
Duration: 01/04/2022 - 30/03/2024

Scientific publications

Highlighted 2024 publications

Wang Y, Li G, Chen B, Shakir G, Volz M, van der Vorst EPC, Maas SL, Geiger M, Jethwa C, Bartelt A, Li Z, Wettich J, Sachs N, Maegdefessel L, Nazari Jahantigh M, Hristov M, Lacy M, Lutz B, Weber C, Herzig S, Guillamat Prats R, Steffens S. Myeloid cannabinoid CB1 receptor deletion confers atheroprotection in male mice by reducing macrophage proliferation in a sex-dependent manner. Cardiovasc Res. 2024 Oct 14;120(12):1411-1426. DOI: 10.1093/cvr/cvae125.

Meiners S, Reynaert NL, Matthaiou AM, Rajesh R, Ahmed E, Guillamat-Prats R, Heijink IH, Cuevas-Ocaña S. The importance of translational science within the respiratory field. Breathe (Sheff). 2024 Mar;20(1):230183. DOI: 10.1183/20734735.0183-2023.

Bianquis C, Leiva Agüero S, Cantero C, Golfe Bonmatí A, González J, Hu X, Lacoste-Palasset T, Livesey A, Guillamat Prats R, Salai G, Sykes DL, Toland S, van Zeller C, Viegas P, Vieira AL, Zaneli S, Karagiannidis C, Fisser C. ERS International Congress 2023: highlights from the Respiratory Intensive Care Assembly. ERJ Open Res. 2024 Apr 22;10(2):00886-2023. DOI: 10.1183/23120541.00886-2023.

ALL PUBLICATIONS

Additional information

Collaborative networks

The group collaborates with several clinicians from the Germans Trias i Pujol University Hospital:

  • Dr Carlos Martinez Rivera in the VIRASMA Project
  • Dr Toni Marín, Dr Irene Aldás, Monica Matute in the VIRUC project

They also have national and international collaborations:

  • Dr Antonio Artigas in Acute Respiratory Disease Syndrome (ARDS) projects
  • Prof Sabine Steffens in cannabinoid system regulation in cardiovascular diseases
  • Prof Donato Santovito in the study of non-coding RNAs in lung diseases

Innovation

Industrial PhD Fellowship Grant.

Outreach

They engage in numerous public outreach activities aimed at non-scientific audiences, participating in initiatives such as #científiques for the International Day of Women and Girls in Science, the European Night of Researchers, Fira STEAM at Badalona, talks at schools for Respiratory Diseases organized by La Marato 3CAT, and events organised by Amics de Can Ruti at the institute.

News

- Success Stories, Outreach

Researchers from IGTP bring science to schools and inspire future generations

In this year’s edition of #científiques, fourteen researchers from IGTP have shared their expertise in various schools and secondary schools across Catalonia, offering students a first-hand and inspiring insight into their work in biomedical research.

Notable presence of IGTP researchers at European Researchers' Night

Several researchers from IGTP took part in this year's European Researchers' Night in Barcelona. They shared their passion for science through talks and led participants of a workshop via a board game into the midst of a tuberculosis epidemic.

+ News