Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer
Research group
Group Leader
Esther Barreiro Portela
Our research is based on the use of patients from clinical settings, animal models of disease, and in vitro primary cultures. We use all kinds of biochemical and cellular and molecular biology techniques (RT-PCR, immunoblotting, immunohistochemistry, 2-D electrophoresis, proteomics analysis, ELISA, activity assays, mitochondrial respiration, flow cytometry, etc.) in order to explore the target mechanisms of our research. The most relevant achievements of our research have been the following: demonstrating that oxidative and nitrosative stress, ubiquitin-proteasome system, NF-kB and FoxO signaling, alterations of epigenetic regulation, and loss of muscle-specific proteins are important players in COPD- and lung cancer-associated cachexia, whereas muscle inflammation does not play a role in this process. Moreover, in the last five years, we have started a new avenue of research focusing on the underlying biology that accounts for the greater susceptibility of patients with chronic respiratory diseases (e.g. COPD) to developing lung tumors. We have demonstrated that increased oxidative stress, inflammatory cytokines and disruption of epigenetic regulation are involved in the greater susceptibility of patients with COPD to developing lung cancer. Finally, we are currently undertaking a new line of research in muscle regeneration. Our first relevant achievement in this area has been the demonstration that there is a decline in the number of satellite cells (SC) following hindlimb immobilization in mice together with an upregulation of markers of SC activation, suggesting that fusion to existing myofibers takes place during unloading. Muscle recovery induces a significant rise in muscle precursor cells and regeneration events along with reduced SC-activation expression markers and a concomitant rise in terminal muscle differentiation expression.
Members
Víctor Curull Serrano (Researcher)
Marisol Domínguez Álvarez (Researcher)
Lara Pijuan Andújar (Researcher)
Alberto Rodríguez Fuster (Researcher)
Albert Sánchez Font (Researcher)
Anna Salazar Degracia (PhD Student)
Main Publications
• Jaitovich A, Barreiro E. Skeletal Muscle Dysfunction in Chronic Obstructive Pulmonary Disease (COPD): What We Know and Can Do for Our Patients. Am J Respir Crit Care Med 2018; 198(2): 175-186. IF 15.239. D1.
• Mateu-Jiménez M, Curull V, Rodríguez-Fuster A, Aguiló R, Sánchez-Font A, Pijuan L, Gea J, Barreiro E. Profile of epigenetic mechanisms in lung tumors of patients with underlying chronic respiratory conditions. Clin Epigenetics 2018; 10: 7. IF 6.091. Q1.
• Millares L, Barreiro E, Cortés R, Martínez-Romero A, Balcells C, Cascante M, Enguita AB, Álvarez C, Rami-Porta R, Sánchez De Cos J, Seijo L, Monsó E, Grupo Colaborativo en Cáncer de Pulmón CIBERES- CIBERONC- SEPAR - Plataforma Biobanco Pulmonar. Tumor-associated metabolic and inflammatory responses in early stage non-small cell lung cancer: Local patterns and prognostic significance. Lung Canc 2018; 122: 124-130. IF 4.486. Q1.
• Tényi Á, Cano I, Marabita F, Kiani N, Kalko SG, Barreiro E, Cascante M, Gómez-Cabrero D, Roca J. Network modules uncover mechanisms of skeletal muscle dysfunction in COPD patients. J Transl Med 2018; 16: 34. IF 4.197. Q1.
• Guitart M, Lloreta J, Mañas-García L, Barreiro E. Muscle regeneration potential and satellite cell activation profile during recovery following hindlimb immobilization in mice. J Cell Physiol 2018; 233(5): 4360-4372. IF 3.923. Q1.
• Sánchez-Font A, Chalela R, Martín-Ontiyuelo C, Albero R, Dalmases A, Longarón R, Alonso-Espinaco V, Curull V, Bellosillo B, Pijuan L. Molecular analysis of peripheral lung adenocarcinoma in brush cytology obtained by EBUS plus fluoroscopy-guided bronchoscopy. Cancer Cytophatol 2018; 126(10): 860-871. IF 3.866. Q1.
• Clavé S, Pijuan L, Casadevall D, Taus A, Gimeno J, Hernández-Llodrà S, Rodríguez M, Lorenzo M, Menéndez S, Albanell J, Espinet B, Arriola E, Salido M. CD274 (PDL1) and JAK2 genomic amplifications in pulmonary squamous-cell and adenocarcinoma patients. Histopathology 2018; 72(2): 259-269. IF 3.267. Q1.
• Barreiro E, Puig-Vilanova E, Salazar-Degracia A, Pascual S, Casadevall C, Gea J. The Phosphodiesterase-4 inhibitor roflumilast reverts proteolysis in skeletal muscle cells of patients with COPD cachexia. J Appl Physiol 2018; 125(2): 287-303. IF 3.256. Q1.
• Greising SM, Ottenheijm CAC, O'Halloran KD, Barreiro E. Diaphragm Plasticity in Aging and Disease: Therapies for Muscle Weakness go from Strength to Strength. J Appl Physiol 2018; 125(2): 243-253. IF 3.256. Q1.
Ongoing Research Projects
• Implicaciones de la respuesta a proteínas desplegadas/ mal desplegadas en la atrofia y disfunción muscular de pacientes con EPOC
- Financing institution: Sociedad Española de Neumología y Cirugía Torácica
- Period: from 2016 to 2019
- Principal investigator: Barreiro Portela, Esther
• Epigenética, microambiente celular y molecular y estroma en la predisposición al cáncer de pulmón en la EPOC: influencia en la supervivencia y valor pronóstico
- Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI14/00713)
- Period: from 2015 to 2019
- Principal investigator: Barreiro Portela, Esther
• Potencial regenerativo de los músculos en pacientes con EPOC y caquexia: papel de las células satélite y su nicho
- Financing institution: SEPAR
- Period: 2018-2020
- Principal investigator: Barreiro Portela, Esther
• Papel del estrés del retículo endoplásmico y PARP en el potencial regenerativo muscular en la sarcopenia asociada a la EPOC y la caquexia cancerosa: implicaciones terapéuticas
- Financing institution: Fondo de Investigaciones Sanitarias. ISCIII (PI18/00075)
- Period: 2019-2021
- Principal investigator: Barreiro Portela, Esther
Participation in Research Networks
• Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES)
- Fondo de Investigación Sanitaria. Subprograma CIBER CB06/06/0043
- Collaborating investigator: Barreiro Portela, Esther
- Principal investigator: Gea Guiral, Joaquim
Group’s Recognitions
• Officially recognised as a consolidated research group by the Generalitat de Catalunya: Unitat de Recerca en Múscul i Aparell Respiratori (URMAR) (2017-2020)
- Agència de Gestió d’Ajuts Universitaris i de Recerca (SGR 442)
- Principal investigator: Barreiro Portela, Esther
Clinical Trials Signed in 2018
• Protocolo RIBRON - Registro Español Informatizado de pacientes con Bronquiectasias
- Register: Protocolo RIBRON
- Principal investigator in our center: Barreiro Portela, Esther
Theses
• Chalela R. Somatic genomic alterations in lung adenocarcinoma: non-invasive molecular diagnosis and prognosis impact of driver mutations in non-tumoral airway cells.
- Universitat Pompeu Fabra
- Directors: Gea Guiral, Joaquim; Curull Serrano, Víctor
- Date of defense: 27/11/2018
C/ Doctor Aiguader, 88
08003 Barcelona
(+34) 93 316 04 00
info@imim.es