About
This 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 fibrosis progress.
Their work has been funded by Instituto de Salud Carlos III (ISCIII), the Agency for Management of University and Research Grants of Generalitat de Catalunya (AGAUR) and the Catalan Society of Pneumology (SOCAP).
Keywords: Pulmonary fibrosis, acute lung injury, immune system, fibroblasts, macrophages, respiratory diseases.
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Group leader
- Raquel Guillamat Prats
Raquel Guillamat Prats
In 2021, Raquel Guillamat initiated the Lung Immunity Translational Research Group at Germans Trias i Pujol Research Institute (IGTP) thanks to a Miguel Servet type program, funded by Instituto de Salud Carlos III. Since then, Guillamat has been leading this research team. As a scientist, she has always been interested in tissue regeneration and the crosstalk between immune cells. Her 5-years postdoctoral work at IPEK- Ludwig-Maximilians-Universität München was directed at elucidating the role of endocannabinoids in vascular diseases, focusing on atherosclerosis and how cannabinoid receptors modulate immune cell behavior. Previously, during her PhD and first postdoctoral stage, Guillamat studied how to repair the epithelial alveolar layer after acute (acute lung injury) or chronic (pulmonary fibrosis) damage. For instance, she explored using cell therapies or anticoagulants to modulate inflammation and cell damage.
Since Guillamat started working in research, she has published more than 30 scientific articles and supervised 4 Ph.D. students, 2 M.D. students, and more than 8 master's theses. She has also participated as a collaborator in 12 national and international research projects with competitive funding and as the principal investigator in 3 projects. Guillamat collaborates with national and international reference researchers in different areas of expertise. At IGTP, she is one of the coffee talk PhD seminar organisers and member of the Internal Scientific Committee. She organised and coordinated the pulmonologists at Germans Trias i Pujol University Hospital (HUGTiP) as a research group, achieving the recongnition as an emergent group by Generalitat de Catalunya (SGR) in 2022. Each year, Guillamat takes part in numerous dissemination activities, such as European Researchers' Night, Scientific Week in Schools, and Girl and Women in Science Day.
Contact: rguillamat(ELIMINAR)@igtp.cat
ORCID: 0000-0001-6960-0985
Team
Clinical researchers
Karina Portillo Carroz, PhD(ELIMINAR)
Paloma Millan Billi(ELIMINAR)
PhD students
Paula Goncalves Romeu(ELIMINAR)
Isabel Alfaya Fiaño(ELIMINAR)
Marina Tuxans
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 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.
Active projects
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
Scientific publications
Highlighted publications
Wang Y, Li G, Chen B, Shakir G, Volz M, van der Vorst EPC, Maas SL, Li Z, Maegdefessel L, Hristov M, Lacy M, Lutz B, Weber C, Herzig S, Guillamat-Prats R, Steffens S. Loss of myeloid cannabinoid CB1 receptor confers atheroprotection by reducing macrophage proliferation and immunometabolic reprogramming. 2024. Accepted in Cardiovascular Research April 2024 (in press). DOI: 10.1101/2023.04.06.535832.
Guillamat-Prats R, Hering D, Derle A, Rami M, Härdtner C, Santovito D, Rinne P, Bindila L, Hristov M, Pagano S, Vuilleumier N, Schmid S, Janjic A, Enard W, Weber C, Maegdefessel L, Faussner A, Hilgendorf I, Steffens S. GPR55 in B cells limits atherosclerosis development and regulates plasma cell maturation. Nat Cardiovasc Res. 2022 Nov;1:1056-1071. DOI: 10.1038/s44161-022-00155-0.
Saigí M, Mesía-Carbonell O, Barbie DA, Guillamat-Prats R. Unraveling the Intricacies of CD73/Adenosine Signaling: The Pulmonary Immune and Stromal Microenvironment in Lung Cancer. Cancers (Basel). 2023 Dec 4;15(23):5706. DOI: 10.3390/cancers15235706.
Guillamat-Prats R. The Role of MSC in Wound Healing, Scarring and Regeneration. Cells. 2021 Jul 8;10(7):1729. DOI: 10.3390/cells10071729.
Guillamat-Prats R, Puig F, Camprubí-Rimblas M, Herrero R, Serrano-Mollar A, Gómez MN, Tijero J, Matthay MA, Blanch L, Artigas A. Intratracheal instillation of alveolar type II cells enhances recovery from acute lung injury in rats. J Heart Lung Transplant. 2018 Jun;37(6):782-791. DOI: 10.1016/j.healun.2017.10.025.
News
IGTP brings science closer to primary school students in Badalona
Researchers from IGTP have taken part in the 2nd Street Science Fair of ESO with a STEAM focus, Together with students from eight secondary schools and other research centres and companies, they have showed scientific concepts to fifth-grade students in Badalona through various workshops.
Can Ruti celebrates a Rare Disease Day symposium highlighting the importance of research to help patients
On Thursday 29 February, the Germans Trias Hospital hosted the 'International Rare Disease Day Symposium'. Health professionals and researchers from the Hospital and IGTP discussed their work in advancing the field of rare diseases. Representatives from patient associations of these diseases also participated.
Contact
(+34) 93 554 30 50 extn: 6540
More links
Follow @rakiphd on Twitter · Donate via Amics de Can Ruti · Follow Raquel Guillamat on LinkedIn