Biophysics and cell therapy in respiratory diseases. PI: Isaac Almendros Lopez

Presentation

Our research activities aim to understand the mechanical behavior of the respiratory system and improve the diagnosis and treatment of respiratory diseases. We study respiratory mechanics using multiscale approaches encompassing the spectrum of organ to molecule. At the organ level, we study the mechanical properties of the airways and lung tissues and the alterations in mechanical function associated with respiratory diseases. At the cellular level, we focus on how the biomechanics of the cell microenvironment, which is considerably modified in the context of respiratory diseases, modulates cell-matrix crosstalk and cell phenotype.

We use basic and translational approaches in a multidisciplinary framework involving close cooperation with clinical research groups working in the field of respiratory medicine. During the last 6 years my group has published more than 100 publications which are mainly focused on three areas:

Area 1: Physiopathology of Obstructive Sleep Apnea​ and its Consequences.
Area 2: Cancer and hypoxia
Area 3: Cell therapy and regenerative medicine

KEYWORDS: respiratory diseases, hypoxia, biomechanics, mechanobiology, extracellular matrix, hydrogels.

Isaac Almendros Lopez
Temporary associate professor
isaac.almendros@ub.edu

Anna Ulldemolins Iglesias
Investigadora pre-doctoral
anna.ulldemolins@ub.edu

Alicia Jurado López
Investigadora pre-doctoral
alicia.jurado@ub.edu

 

Maria Leonor Narciso
Investigadora pre-doctoral
mnarciso@ibecbarcelona.eu 

  • Area 1: Physiopathology of Obstructive Sleep Apnea​ and its Consequences

Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder among adult population and is characterized by an increased collapsibility of the upper airway promoting recurrent occlusions during sleep hours leading to intermittent hypoxia (IH) and sleep fragmentation (SF). The most common risk factors of OSA are age, male gender and obesity.

My group belongs to the Spanish Sleep Network. During the last years and we have started an active and proliferative collaboration with Dr. Gozal at the University of Missouri. Our expertise in bioengineering allowed the development of new in vitro and in vivo translational models to better understand the pathophysiology of obstructive sleep apnea. These models have been crucial to study in more detail the effects of sleep fragmentation, intermittent hypoxia and hypercapnia in the cardiovascular, cognitive, metabolic and recently cancer adverse outcomes observed in OSA patients.

  • Area 2: Cancer and hypoxia

In 2012, our lab showed for the first time that intermittent hypoxia similar to that suffered by OSA patients is able to promote tumor growth, invasiveness and metastasis. This work posed a new challenge in the field of OSA, opening a new perspective unexplored to date. Those findings served as proof of concept of the epidemiological studies published later, revealing an independent association between OSA and cancer.

  • Area 3: Cell therapy and regenerative medicine
We are currently investigating the development of natural scaffolds from decellularized lungs to better understand the role of the extracellular matrix in the development of respiratory diseases such as fibrosis, lung cancer and emphysema. These models will provide a more realistic environment to understand all the mechanisms involved in these respiratory diseases. Novel lung-derived hydrogels will be used to understand the role of the mechanical stimuli in the lungs to differentiate and improve the therapeutic potential of stem cells after acute lung injury.

Hidrogeles de matriz extracelular pulmonar para preacondicionamiento e instilación de células madre mesenquimales en el tratamiento de enfermedades respiratorias severas

Funding entity: Ministerio de Ciencia e Innovación    
Project Code: PID2019-108958RB-I00
Principal investigator/s: Isaac Almendros López
Amount: 169.400 €
Period: from 2020 to 2023   

Mecanismos hipóxicos en el cáncer de pulmón en “overlap síndrome”: papel de la matriz extracelular tumoral en un modelo murino que integra cáncer pulmonar, EPOC y SAOS

Funding entity: SEPAR    
Project Code: 900/2019  
Principal investigator/s: Isaac Almendros López
Amount: 9.000 €
Period: from 2020 to 2023 

Efecto de la apnea del sueño y/o insuficiencia respiratoria en la agresividad de diferentes estirpes de cancer de pulmón humano

Funding entity: SEPAR    
Project Code: 595/2017
Principal investigator/s: Isaac Almendros López
Amount: 12.000 €
Durada: from 2018 to 2021   

Efectos de la hipoxia/hipercapnia en la interacción biomecánica célula-matriz pulmonar en la progresión de las enfermedades respiratorias

Funding entity: Ministerio de Economia y Competitividad
Project Code: SAF2017-85574-R    
Principal investigator/s: Ramon Farré Ventura and Isaac Almendros López
Amount: 217.800 €
Period: des de/d’ 2018 fins a 2020   

Fisiopatologia i tractament de les malalties respiratòries

Funding entity: Generalitat de Catalunya (AGAUR)    
Project Code: 2017SGR787 
Principal investigator/s: Antoni Torres Martí
Amount: 35.200 €
Period: from 2017 to 2021

Alteraciones del citosqueleto y de la matriz extracelular cerebral características de la enfermedad de Alzheimer en un modelo celular y animal de apnea obstructiva del sueño

Funding entity: SEPAR    
Project Code: 139/2015
Principal investigator/s: Isaac Almendros López
Amount: 12.000 €
Period: from 2016 to 2019

Impact of Obstructive sleep apnea in the evolution of Alzheimer Disease. Role of hypoxia and sleep fragmentation

Funding entity: FMTV - Fundació La Marató de TV3    
Project Code: 20143231 
Principal investigator/s: Ramon Farré Ventura
Amount: 134.987,50 €
Period: from 2015 to 2018  

Papel de la Prostaglandina-E2 en el Desarrollo Tumoral Inducido por la Hipoxia Intermitente en un Modelo de Apnea del Sueño en Ratón y sus Posibilidades Terapéuticas

Funding entity: SEPAR    
Project Code: 084/2014  
Principal investigator/s: Isaac Almendros López
Amount: 18.000 €
Period: from 2015 to 2018 

Effect of intermittent hypoxia and its interaction with obesity in tumor progression in an animal model of obstructive sleep apnea

Funding entity: SEPAR    
Project Code: SEPAR 2011
Principal investigator/s: Isaac Almendros López
Amount: 12.000 €
Period: from 2011 to 2014

For more information for PI publications click in the link:
SCOPUS Author ID: 8892633900
ORCID: 0000-0002-1998-937
h-index: 36

 

Ulldemolins A, Jurado A, Herranz-Diez C, Gavara N, Otero J, Farré R, Almendros I. Lung Extracellular Matrix Hydrogels-Derived Vesicles Contribute to Epithelial Lung Repair. Polymers (Basel). 2022 Nov 14;14(22): 4907. doi: 10.3390/ polym14224907. PMID: 36433034

Petzold T, Zhang Z, Ballesteros I, Saleh I, Polzin A, Thienel M, Liu L, Ul Ain Q, Ehreiser V, Weber C, Kilani B, Mertsch P, Götschke J, Cremer S, Fu W, Lorenz M, Ishikawa-Ankerhold H, Raatz E, El-Nemr S, Görlach A, Marhuenda E, Stark K, Pircher J, Stegner D, Gieger C, Schmidt-Supprian M, Gaertner F, Almendros I, Kelm M, Schulz C, Hidalgo A, Massberg S. Neutrophil "plucking" on megakaryocytes drives platelet production and boosts cardiovascular disease. Immunity. 2022 Oct 18; S1074-7613(22) 00542-8. doi: 10.1016/ j.immuni.2022.10.001. PMID: 36272416

Buj-Corral I, Sanz-Fraile H, Ulldemolins A, Tejo-Otero A, Domínguez-Fernández A, Almendros I, Otero J. Characterization of 3D Printed Metal-PLA Composite Scaffolds for Biomedical Applications. Polymers (Basel). 2022 Jul 5; 14(13): 2754. doi: 10.3390/ polym14132754. PMID: 35808799

Falcones B, Söderlund Z, Ibáñez-Fonseca A, Almendros I, Otero J, Farré R, Rolandsson Enes S, Elowsson Rendin L, Westergren-Thorsson G. hLMSC Secretome Affects Macrophage Activity Differentially Depending on Lung-Mimetic Environments. Cells. 2022 Jun 8; 11(12): 1866. doi: 10.3390/ cells11121866. PMID: 35740995

Marhuenda E, Villarino A, Narciso ML, Camprubí-Rimblas M, Farré R, Gavara N, Artigas A, Almendros I, Otero J. Lung Extracellular Matrix Hydrogels Enhance Preservation of Type II Phenotype in Primary Alveolar Epithelial Cells. Int J Mol Sci. 2022 Apr 28;23(9): 4888. doi: 10.3390/ ijms23094888. PMID: 35563279

Narciso M, Ulldemolins A, Júnior C, Otero J, Navajas D, Farré R, Gavara N, Almendros I. Novel Decellularization Method for Tissue Slices. Front Bioeng Biotechnol. 2022 Mar 9;10: 832178. doi: 10.3389/ fbioe.2022.832178. eCollection 2022. PMID: 35356779

Farré R, Gozal D, Almendros I. Human experimental models: seeking to enhance multiscale research in sleep apnoea. Eur Respir J. 2021 Oct 7; 58(4): 2101169. doi: 10.1183/ 13993003.01169-2021. PMID: 34620681

Otero J, Ulldemolins A, Farré R, Almendros I. Oxygen Biosensors and Control in 3D Physiomimetic Experimental Models. Antioxidants (Basel). 2021 Jul 22; 10(8): 1165. doi: 10.3390/ antiox10081165. PMID: 34439413

Andreu I, Falcones B, Hurst S, Chahare N, Quiroga X, Le Roux AL, Kechagia Z, Beedle AEM, Elosegui-Artola A, Trepat X, Farré R, Betz T, Almendros I, Roca-Cusachs P. The force loading rate drives cell mechanosensing through both reinforcement and cytoskeletal softening. Nat Commun. 2021 Jul 9; 12(1): 4229. doi: 10.1038/ s41467-021-24383-3. PMID: 34244477

Rey E, Del Pozo-Maroto E, Marañón P, Beeler B, García-García Y, Landete P, Isaza SC, Farré R, García-Monzón C, Almendros I, González-Rodríguez Á. Intrahepatic Expression of Fatty Acid Translocase CD36 Is Increased in Obstructive Sleep Apnea. Front Med (Lausanne).2020 Aug 11; 7:450. doi: 10.3389/ fmed.2020.00450. eCollection 2020. PMID: 32850919

  • Offers from the University of Barcelona:

Feina UB

  • Offers from the Research Group:

Currently, we do not have any openings. However, if you are a highly motivated student or postdoc, do not hesitate to contact at isaac.almendros@ub.edu

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