StroomaLab: Translational Microenvironment Research in Lung Cancer and Lung Fibrosis

Research interests overview

The stroma is the connective tissue rich in fibroblasts and a collagenous extracellular matrix (ECM) that surrounds epithelial cells and provides key biomechanical and biochemical cues to guide normal development, repair and tissue-specific functions. Conversely, stromal composition and associated signaling becomes chronically awry in prevalent and fatal diseases like cancer and organ fibrosis. In the context of the lung, a hallmark of both lung cancer and pulmonary fibrosis is a persistent desmoplastic stroma rich in activated fibroblasts/myofibroblasts in the background of an excessive deposition of fibrillar collagens, which has been implicated in virtually all steps of disease progression and resistance to therapies. Our lab aims to understand the origins of the pathologic fibrotic stroma both in the context of the primary tumor and brain metastasis, how it contributes to disease progression, how can it be targeted therapeutically, and how can it be used to identify clinically-relevant biomarkers. For this purpose, we combine cutting-edge preclinical models (in culture, in vivo and ex-vivo) based on patient-derived samples (including primary fibroblasts and tissue samples from patients with lung cancer or idiopathic pulmonary fibrosis), state-of-the-art molecular and cell biology techniques (including “omics”), and bioengineering approaches (mainly atomic force microscopy, microfluidics and digital pathology). We then apply these tools to study quantitatively the aberrant interactions between fibroblasts and other stromal cells (immune cells, endothelial cells) or epithelial cells as well as the aberrant collagenous ECM and associated mechanobiology. Our ultimate goal is to be translational and bring our knowledge to clinical settings, and to this aim we have ongoing collaborations with clinical groups and collaborate with companies to check the suitability of novel drugs against the aberrant stroma as well as novel biomarker for improve diagnosis, prognosis and therapeutic guidance.

For more specifics about our past and current research, please browse the different sections below:

[LAB MEMBERS] [RESEARCH] [PUBLICATIONS] [COLLABORATION WITH INDUSTRY]

[NEWS&VIEWS] [COLLABORATORS] [OPENINGS] [TEACHING] [CONTACT]

[SUPORT LUNG CANCER RESEARCH / DONAR SUPORT RECERCA CÀNCER DE PULMÓ]

LAB MEMBERS

Jordi Alcaraz (Principal Investigator)

Brief CV

· Citizenship: Spain

· Education:

- Ph.D. in Biophysics, University of Barcelona, Barcelona (Spain) 2002

- M. Sc. in Cell Physiology, University of Barcelona, Barcelona (Spain) 2000

- B. Sc. in Physics, University of Barcelona, Barcelona (Spain) 1997

· Biosketch:

Jordi is a Serra-Húnter Associate Professor in the School of Medicine at the University of Barcelona (UB) since 2016. He graduated in Physics in 1997 at the UB, and attended graduate school at the same university, where he obtained his Ph.D. in the fields of Cellular Biophysics and Nanobioengineering in 2002. From 2002 until 2007 he was a joint postdoc between the Cancer Biology Laboratory of Dr Mina J Bissell at the Lawrence Berkeley National Laboratory and the Single Molecule Biophysics Laboratory of Prof Carlos Bustamante at UC Berkeley. During his postdoc he pursued research aiming to understand how biophysical cues from the tissue microenvironment control differentiation and cancer progression at the single cell level. He is also an associate group leader at the Institute for Bioengineering of Catalonia (IBEC) and a core member of the Functional Unit of Thoracic Tumors at the Hospital Clinic de Barcelona.

· More at:

ORCID:0000-0001-7898-1599

Linkedin profile

Google Scholar

jalcaraz@ub.edu

Office Ph: (+34) 934031148

Lab Ph: (+34) 934039764

Fax: (+34) 934035278

Address:

Unitat de Biofísica i Bioenginyeria

Facultat de Medicina Universitat de Barcelona

Casanova 143

08036 Barcelona, Spain

Graduate students (director/tutor)

Paula Duch

Brief CV

· Citizenship: Spain

· Education:

- M. Sc. in Biomedical Research, University Pompeu Fabra, Barcelona (Spain) 2021

- B. Sc. in Biotechnology, Universidad de Oviedo, Oviedo (Spain), 2020

abernardo@ub.edu

(+34) 934039764

Victoria Batto

Brief CV

· Citizenship: Argentina/Spain

· Education:

- M. Sc. in Biotecnology, Universidad de Buenos Aires, Buenos Aires (Argentina), 2022

- B. Sc. In Chemical Sciences, Universidad de Buenos Aires, Buenos Aires (Argentina), 2017

victoriabatto@ub.edu

(+34) 934039764

Teia Vallès

Brief CV

· Citizenship: Spain

· Education:

- M. Sc. in TraBiomedicine, University of Barcelona, Barcelona (Spain) 2018

- B. Sc. in Biomedical Sciences, , University of Barcelona, Barcelona (Spain) 2023

tvalles@ub.edu

(+34) 934039764

Elba Marín

Brief CV

· Citizenship: Spain

· Education:

- M. Sc. in Translational Medicine, University of Barcelona, Barcelona (Spain) 2018

- B. Sc. in Biomedical Sciences, , University of Barcelona, Barcelona (Spain) 2017

elmarin@clinic.cat

(+34) 934039764

Postdoctoral Researchers

Patricia Fernández

Brief CV

· Citizenship: Spain

· Education:

- PhD in Biomedicine, University of Barcelona, Barcelona (Spain) 2016

- M. Sc. in Biomedicine, University of Barcelona, Barcelona (Spain) 2010

- B. Sc. in Biochemistry, Autonomous University of Barcelona, Barcelona (Spain) 2009

- B. Sc. in Biology, Autonomous University of Barcelona, Barcelona (Spain) 2008

pfernandezn@ub.edu

(+34) 934039764

Natalia Díaz

Brief CV

· Citizenship: Chile/Spain

· Education:

- PhD in Biochemistry, Universidad de Chile, Santiago (Chile) 2016

- M. Sc. in Biochemistry, Pontificia Universidad Católica de Valparaíso, Valparaíso (Chile) 2010

- B. Sc. In Science, Pontificia Universidad Católica de Valparaíso, Valparaíso (Chile) 2007

nataliadiazvaldivia@gmail.com

(+34) 934039764

Marc Rico-Pastó

Brief CV

· Citizenship: Spain

· Education:

- PhD in Physics, University of Barcelona, Barcelona (Spain) 2022

- M. Sc. in Photonics, Polytechnic University of Catalonia, Barcelona (Spain) 2014

- B. Sc. in Physics, University of Barcelona, Barcelona (Spain) 2013

mricopasto@ub.edu

(+34) 934039764

Marselina Arshakyan

Brief CV

· Citizenship: Armenia

· Education:

- PhD in Biochemical and Pharmacological Methodologies, University of Urbino Carlo Bo, Urbino (Italy) 2015

- Master's degree in Pharmaceutical Chemistry, Pharmaceutics, Yerevan State University, Yerevan (Armenia) 2004

m.arshakyan@ub.edu

(+34) 934039764

Past Members

NAME	Current Position
Enrico Almici (grad student), 2022	Product Manager Digital Healthcare Dept - Antares Vision Group (Italy)
Paula Duch (grad student), 2022	Postdoc, University of Glasgow (UK)
Marta Gabasa (postdoc), 2023	Telomere Therapeutics, Barcelona
Rafael Ikemori (postdoc), 2022	Clinical Research Associate II, MSc-PhD at Grupo Español de Cáncer de Pulmón, Barcelona
Alejandro Llorente (grad student), 2022	FAS Europe Region in Yikon Genomics, Barcelona
Alícia Giménez (grad student), 2015	Senior Scientific Editor \| Expert in Educational Program Design and Medical Training
Roberto Lugo (grad student), 2014	Biomedical Researcher at Hospital Regional de Alta Especialidad de la Península de Yucatán, Mexico
Marta Puig (grad student), 2014	Product Manager Rheumatology at Gedeon Richter - PregLem
Roland Galgoczy (grad student), 2014	Independent Consultant - Life Sciences, CompX Health (UK)
Irene Acerbi (grad student), 2010	Management / Clinical Operations in Cancer, Exai Bio, San Francisco (US)
Adai Colom (technician), 2010	Principal Investigator at Fundación Biofísica Bizkaia / Biofisika Bizkaia Fundazioa

RESEARCH

Current research projects and long-term research interests

Aberrant cancer-stroma interactions in lung cancer

Lung cancer remains the leading cause of cancer-related deaths worldwide, with a 5-year survival rate of only 23% that is much lower than other leading cancer types like breast (91%) or colon (63%). Lung tumors and other solid neoplasias are increasingly regarded as organs driven by the aberrant co-evolution of cancer and stromal cells. Based on the striking similarities between the stroma in tumors and wounds, tumors are often described as “wounds that never heal”, and the desmoplastic (wound-like) stroma is pointed as a major contributor to virtually all steps of tumor progression, including metastasis formation, and even resistance to therapies. However, the mechanisms underlying the effects of such tumor stroma on tumor/metastasis-promotion and modulation of therapy responses, including immune checkpoint inhibitors, remain poorly understood, particularly in lung cancer. To address this limitation, we started in 2010 a collection of tumor associated fibroblasts (TAFs) -the most abundant stromal cell type- from surgical patients of the Hospital Clínic de Barcelona diagnosed with non-small cell lung cancer (NSCLC), which is the most abundant lung cancer type. Likewise, we gathered biopsies from a cohort of primary tumors and paired brain metastasis to unravel the presence of TAFs in the common dissemination of lung tumors to the brain. We use advanced pre-clinical culture models to study the aberrant interactions between TAFs and cancer cells or other stromal cells (immune cells, endothelial cells) in lung cancer to unveil key molecular alterations that can be useful to develop novel therapies, to identify novel biomarkers and to dissect resistance mechanisms to current therapies.

Role of abnormal tissue mechanics in fibrosis and cancer

It is well known that each tissue and organ in our body is characterized by a specific deformability or “stiffness”. Thus, our brain or lungs are soft organs, whereas our muscle and bones are stiff. In normal conditions, the stiffness of each tissue is maintained within its physiological range during adulthood. Occasionally, a region of a tissue may temporarily stiffen as part of the normal wound healing response to damage. Likewise, tissue stiffness becomes progressively altered during aging. None of these previously mentioned mechanical alterations compromise neither the integrity nor the normal function of the tissue. In contrast, a hallmark of numerous diseases is the permanent loss of normal tissue stiffness, concomitantly with an impairment of normal functions. In some cases, the tissue becomes globally more stiff as in sclerosis, fibrosis and cancer. In cancer, tissue stiffening has been associated with the excessive abundance of activated TAFs and subsequent deposition of fibrillar collagens. Intriguingly, a fraction of cancer cells may become abnormally soft and hyperflexible, eliciting a mechanical advantage to promote dissemination. We are particularly interested in how normal tissue stiffness is lost in fibrosis and cancer, how this abnormal tissue hardening contributes to the progression of these devastating diseases or resistance to therapies, and how some cancer cells acquire an hyperflexible phenotype to enhance their dissemination. Moreover, we are interested in using tissue mechanics-associated features as novel diagnostic and/or prognostic biomarkers. To pursue these interests, we use advanced models based on biomaterials with tunable elasticity and microfluidics as well as Atomic force microscopy (AFM) and other nanomechanical tools that enable measuring cell and tissue mechanics with high resolution.

Understanding how the collagenous ECM contributes to tumor progression and formation of brain metastasis

We previously reported that the high deposition of fibrillar collagens is associated with poor prognosis independently of the TNM staging in NSCLC. However, how the collagen-rich ECM contributes to tumor progression remains poorly understood. We are interested in understanding how the collagenous stroma promotes immunosuppression and the acquisition of an invasive phenotype, both in the context of the primary tumor and brain metastasis, which is a common metastatic organ in NSCLC.

Experimental approaches and areas of expertise

Our research is intrinsically multidisciplinary, as it integrates tools and techniques from a variety of scientific fields including molecular and cell biology, biomaterials, nanobiotechnology and biophysics.

The sources of our cells (both human and rodent) are either primary culture from donors or commercially available cell lines. We have also developed an ex-vivo assay based on precision cut thin slices of fresh tumors from surgical lung cancer patients to directly test patient response to selected drugs.

The main techniques we use in our research include the following (but are not restricted to):

· Cell culture: primary culture of fibroblasts from tissue explants, culture of cell lines of mesenchymal or epithelial origin

· Genetic tools for transcription manipulation: shRNA, siRNA

· Biomaterials: 2D and 3D gel assays in which both the biochemical composition and the mechanical properties can be controlled independently

· Molecular cell biology: qRT-PCR, Western-Blotting, Immunofluorescence, Immunohistochemistry, Zymmography, Flow Cytometry, ELISA

· Tools to model the hydrodynamic features within the circulation: micropatterning

· Advanced optical microscopy: phase contrast microscopy, DIC, epifluorescence, polarized light microscopy, confocal microscopy and confocal reflection microscopy

· Image processing with Image J, quPATH, Matlab

· Digital Pathology, with customized software to process histologic stainings from patients (in bright-field and immunofluorescence) and collagen architecture (with CT-FIRE)

· Bioinformatic analysis, including analysis of gene expression datasets available at TCGA, scRNAseq or other databases, pathway enrichment analysis, interactome analysis etc.

· Nano- Microrheology (i.e. characterization of mechanical properties of soft samples, including cells, gels and tissues) with Atomic Force Microscopy

· Theoretical Physics: Soft Condensed Matter and Contact Mechanics

UP

CURRENT AND PAST FUNDING SOURCES (competitive calls)

• Agencia Estatal de Investigación AEI, Spain

• Instituto de Salud Carlos III ISCIII, Spain

• Asociación Española Contra el Cáncer AECC, Spain

• FET-OPEN, Horizon 2020, European Union

• ERA-NET Transcan-3, European Union

• Sociedad Española de Neumología y Cirugía Torácica SEPAR, Spain

PUBLICATIONS

Alejandro Rosell, Agata A Krygowska, Marta Alcón Pérez, Cristina Cuesta, Mathieu-Benoit Voisin, Juan de Paz, Héctor Sanz-Fraile, Vinothini Rajeeve, Alberto Berral-González, Ana Carreras-González, Ottilie Swinyard, Enrique Gabandé-Rodriguez, Julian Downward, Jordi Alcaraz, Juan Anguita, Carmen García-Macías, Javier De Las Rivas, Pedro Cutillas, Esther Castellano. AS-p110a signalling in macrophages is required for effective inflammatory response and resolution of inflammation. eLife 2024 13:RP94590. doi.org/10.7554/eLife.94590.2 LINK

P. Duch, N. Díaz-Valdivia, M. Gabasa, R. Ikemori, M. Arshakyan, P. Fernández-Nogueira, A. Llorente, C. Teixido, J. Ramírez, J. Pereda, L. Chuliá-Peris, J. M. Galbis, F. Hilberg, N. Reguart, D.C. Radisky, J. Alcaraz. Aberrant TIMP-1 production in tumor-associated fibroblasts drives the selective therapeutic effects of nintedanib in lung adenocarcinoma. Cancer Science 2024 115(5):1505-1519 PMID: 38476010 DOI: 10.1111/cas.16141 LINK

M. Narciso, Á. Martínez, C. Júnior, N. Díaz-Valdivia, A. Ulldemolins, M. Berardi, K. Neal, D. Navajas, R. Farré, J. Alcaraz, I. Almendros, N. Gavara. Lung Micrometastases Display ECM Depletion and Softening While Macrometastases Are 30-Fold Stiffer and Enriched in Fibronectin. Cancers (Basel) 2023 15(8):2404. doi: 10.3390/cancers15082404. PMID: 37190331 LINK

E. Almici, M. Arshakyan, J.Ll Carrasco, A. Martínez, J. Ramírez, A. B. Enguita, E. Monsó, J. Montero, J. Samitier, J. Alcaraz. Quantitative image analysis of fibrillar collagens reveals novel diagnostic and prognostic biomarkers and histotype-dependent aberrant mechanobiology in lung cancer. 2023 Mod Pathol. 2023 Jul;36(7):100155. doi: 10.1016/j.modpat.2023.100155. PMID: 36918057 LINK

Y. Juste-Lanas, N. Díaz-Valdivia, A. Llorente, R. Ikemori, A. Bernardo, M. Arshakyan, C. Borau, J. Ramírez, J.C. Ruffinelli, E. Nadal, N. Reguart, J. M. García-Aznar, J. Alcaraz (corresponding). 3D collagen migration patterns reveal a SMAD3-dependent and TGF-β1-independent mechanism of recruitment for tumor associated fibroblasts in lung adenocarcinoma. Br J Cancer 2023 128(6):967-981 2022 (doi 10.1038/s41416-022-02093-x) PMID: 36572730 LINK

P. Duch., N. Díaz-Valdivia, R. Ikemori, M. Gabasa, E.S. Radisky, M. Arshakyan, S. Gea-Sorlí, A. Mateu, P..Bragado, H. Mori, J. Ramírez, C. Teixidó, N. Reguart, C..Fillat, D. Radisky, J. Alcaraz. Aberrant TIMP-1 overexpression in tumor-associated fibroblasts drives tumor progression through CD63 in lung adenocarcinoma. Matrix Biology 2022, 111: 207-225 PMID: 35787446 LINK

Lourdes Chuliá-Peris, Cristina Carreres-Rey, Marta Gabasa, Jordi Alcaraz, Julián Carretero, Javier Pereda. Matrix metalloproteinases and their inhibitors in pulmonary fibrosis: EMMPRIN/CD147 comes into play. Int. J. Mol. Sci. 2022, 23(13):6894 DOI: 10.3390/ijms23136894 LINK

J. Alcaraz, R. Ikemori, A. Llorente, N. Díaz-Valdivia, N. Reguart, M. Vizoso. Epigenetic reprogramming of tumor-associated fibroblasts in lung cancer: therapeutic opportunities. Cancers (Basel) 2021, 13:3782-3802. DOI: 10.3390/cancers13153782 LINK

M. Gabasa, E. Radisky, R. Ikemori, G. Bertolini, M. Arshakyan., A. Hockla, P. Duch., O. Rondinone, A. Llorente, M. Maqueda, A. Davalos, E. Gavilán, A. Perera, J. Ramírez, P. Gascón, N. Reguart, L. Roz., D.C. Radisky, J. Alcaraz. MMP1 drives tumor progression in large cell carcinoma of the lung through fibroblast senescence. Cancer Letters 2021, 507:1-12 PMID: 33684534 LINK

M. Gabasa; M. Arshakyan; A. Llorente; L. Chuliá-Peris; I. Pavelescu; A. Xaubet; J. Pereda; J. Alcaraz. Interleukin-1β Modulation of the Mechanobiology of Primary Human Pulmonary Fibroblasts: Potential Implications in Lung Repair. Int. J. Mol. Sci. 2020, 21, 8417 LINK

Epigenetic SMAD3 repression in tumor-associated fibroblasts impairs fibrosis and response to the antifibrotic drug nintedanib in lung squamous cell carcinoma. R. Ikemori, M. Gabasa, P. Duch, M. Vizoso, P. Bragado, M. Arshakyan, I-C. Benchea, A. Marín, S. Morán, M. Castro, G. Fuster, S. Gea-Sorli, T. Jauset, L. Soucek, L.M. Montuenga, M. Esteller, E. Monsó, V.I. Peinado, P. Gascón, C. Fillat, F. Hilberg, N. Reguart, J. Alcaraz. Cancer Res 2020 80:276-290 LINK

J. Alcaraz, J. Lluís Carrasco, L. Millares, I-C. Luis, F.J. Fernández-Porras, A. Martinez-Romero, N. Diaz-Valdivia, J. Sanchez De Cos, R. Rami-Porta, L. Seijo, J. Ramírez, M.J. Pajares, N. Reguart, E. Barreiro, E. Monsó. Stromal markers of activated tumor associated fibroblasts predict poor survival and are associated with necrosis in non-small cell lung cancer. Lung Cancer 2019, 135: 151–160 LINK

Esther Marhuenda, Noelia Campillo, Marta Gabasa, Miguel Angel Martínez-García, Francisco Campos-Rodríguez, David Gozal, Daniel Navajas, Jordi Alcaraz, Ramon Farré, Isaac Almendros. Effects of Sustained and Intermittent Hypoxia on Human Lung Cancer Cells. American Journal of Respiratory Cell and Molecular Biology 2019;61(4):540-544 LINK

Laura Sala, Héctor Franco-Valls, Jelena Stanisavljevic, Josue Curto, Jordi Vergés, Raúl Peña, Paula Duch,

Jordi Alcaraz, Antonio G. de Herreros and Josep Baulida. Abrogation of myofibroblast activities in metastasis and fibrosis by methyltransferase inhibition. International Journal of Cancer 2019 145:3064-3077 doi: 10.1002/ijc.32376. LINK

Characterization of the elastic properties of extracellular matrix models by atomic force microscopy. J. Otero, D. Navajas, J. Alcaraz. Methods in Cell Biology: Cell-derived Matrices Part A 2019 doi.org/10.1016/bs.mcb.2019.11.016 LINK

A. Giménez, P. Duch, M. Puig, M. Gabasa, A. Xaubet, J. Alcaraz. Dysregulated collagen homeostasis by matrix stiffening and TGF-β1 in fibroblasts from idiopathic pulmonary fibrosis patients: role of FAK/Akt. International Journal of Molecular Science 2017, 18(11), 2431; pii: E2431 LINK

M. Gabasa, P. Duch, I. Jorba, A. Giménez, R. Lugo, I. Pavelescu, F. Rodríguez-Pascual, M. Molina-Molina, A. Xaubet, J. Pereda, J. Alcaraz. Epithelial contribution to the pro-fibrotic stiff microenvironment and myofibroblast population in lung fibrosis. Molecular Biology of the Cell 2017, 28(26):3741-3755 LINK

M. Gabasa, R. Ikemori, F. Hilberg, N. Reguart, J. Alcaraz. Nintedanib selectively inhibits the activation and tumor-promoting effects of fibroblasts from lung adenocarcinoma patients. British Journal of Cancer 2017, 117:1128-1138 LINK

A. Labernadie, T. Kato, A. Brugués, X. Serra-Picamal, S. Derzsi, V. Gonzalez, A. Elosegui-Artola, J. Alcaraz, P. Roca-Cusachs, E. Sahai, X. Trepat. A mechanically active heterophilic E-cadherin/N-cadherin adhesion enables cancer associated fibroblasts to drive cancer cell invasion. Nature Cell Biology 2017, 19: 224–237 LINK

J. Alcaraz, J. Otero, I. Jorba, D. Navajas. Bidirectional mechanobiology between cells and their local extracellular matrix probed by atomic force microscopy. Seminars in Cell and Developmental Biology 2017, S1084-9521(17)30328-2 LINK

A. Giménez, J.J Uriarte, J. Vieyra, D. Navajas, J. Alcaraz. Elastic properties of hydrogels and decellularized tissue sections used in mechanobiology studies probed by atomic force microscopy. Microsc Res Tech. 2017;80:85-96. LINK

R. Lugo, M. Gabasa, F. Andriani, M. Puig, F. Facchinetti, J. Ramírez, A. Gómez-Caro, U. Pastorino, G. Fuster, I. Almendros, P. Gascón, A. Davalos, N. Reguart, L. Roz, J. Alcaraz. Heterotypic paracrine signaling drives fibroblast senescence and tumor progression of large cell carcinoma of the lung. Oncotarget 2016 7(50):82324-82337 LINK

M. Vizoso, M. Puig, F.J. Carmona, M. Maqueda, A. Velásquez, A. Gómez, A. Labernadie, R. Lugo, M. Gabasa, L.G. Rigat-Brugarolas, X. Trepat, J. Ramírez, N. Reguart, S. Moran, A. Perera, M. Esteller, J. Alcaraz. Aberrant DNA methylation in Non Small Cell Lung Cancer associated fibroblasts. Carcinogenesis 2015, 36:1453-63 LINK

E. Monsó, L.M. Montuenga, J. Sánchez de Cos, C. Villena, and Grupo Colaborativo en Cáncer de Pulmón

CIBERES-RTICC-SEPAR-Plataforma Biobanco Pulmonar (J. Alcaraz et al.), Biological Marker Analysis as Part of the CIBERES-RTIC Cancer-SEPAR Strategic Project on Lung Cancer. Arch Bronconeumol, 2015 51(9):462-467 LINK

V. Vicens-Zygmunt, S. Estany, A. Colom, A. Montes-Worboys, C. Machahua, A.J. Sanabria, R. Llatjos, I. Escobar, F. Manresa, J. Dorca, D. Navajas, J. Alcaraz, M. Molina-Molina. Fibroblast viability and phenotypic changes within glycated stiffened three-dimensional collagen matrices. Respiratory Research 2015 Jul 1;16:82 LINK

M. Puig, R. Lugo, M. Gabasa, A. Giménez, A. Velásquez, R. Galgoczy, J. Ramírez, A. Gómez-Caro, Ó. Busnadiego, F. Rodríguez-Pascual, P. Gascón, N. Reguart, J. Alcaraz. Matrix Stiffening and Beta1 integrin Drive Subtype-specific Fibroblast Accumulation in Lung Cancer. Mol Cancer Res 2015, 13:161-73. LINK

R. Galgoczy, I. Pastor, A. Coloma, A. Giménez, F. Mas, J. Alcaraz. A spectrophotometer-based diffusivity assay reveals that diffusion hindrance of small molecules in extracellular matrix gels used in 3D cultures is dominated by viscous effects. Colloids and Surfaces B: Biointerfaces 2014, 120:200-7 LINK

Colom A, Galgoczy R, Almendros I, Xaubet A, Farré R, Alcaraz J. Oxygen diffusion and consumption in extracellular matrix gels: Implications for designing three-dimensional cultures. J Biomed Mater Res A. 2014, 102:2776-84 LINK

I. Acerbi, T. Luque, A. Giménez, M. Puig, N. Reguart, R. Farré, D. Navajas, and J. Alcaraz. Integrin-Specific Mechanoresponses to Compression and Tension Probed by cylindrical Flat-Ended AFM Tips in Lung Cells. PLoS ONE 2012, 7: e32261 LINK

Mori H, Lo AT, Inman JL, Alcaraz J, Ghajar CM, Mott JD, Nelson CM, Chen CS, Zhang H, Bascom JL, Seiki M, Bissell MJ. Transmembrane/cytoplasmic, rather than catalytic, domains of Mmp14 signal to MAPK activation and mammary branching morphogenesis via binding to integrin β1. Development. 2013, 140:343-52 LINK

J. Alcaraz, H. Mori, C.M. Ghajar, D. Brownfield, R. Galgoczy and M.J. Bissell. Collective epithelial cell invasion overcomes mechanical barriers of collagenous extracellular matrix by a narrow tube-like geometry and MMP14-dependent local softening. Integr. Biol., 2011, 3:1153–1166 LINK

J. Alcaraz, R. Xu, H. Mori, C.M. Nelson, R. Mroue, V.A. Spencer, D. Brownfield, D.C. Radisky, C. Bustamante, M.J. Bissell. Laminin and biomimetic extracellular elasticity enhance functional differentiation in mammary epithelia EMBO J. 2008, 27:2829-2838 LINK

P. Roca-Cusachs, J. Alcaraz, R. Sunyer, J. Samitier, R. Farré, D. Navajas. Micropatterning of single endothelial cell shape reveals a tight coupling between nuclear volume in G1 and proliferation. Biophys J, 2008, 94:4984-4995 LINK

J. LeBeyec, R. Xu, S.Y. Moonlee, C.M. Nelson, A. Rizki, J. Alcaraz, M.J. Bissell. Cell shape regulates global histone acetylation in human mammary epithelial cells. Exp Cell Res. 2007,313:3066-3075 LINK

F. Rico, J. Alcaraz, J.J. Fredberg, D. Navajas. Nanomechanics of lung epithelial cells. Int J of Nanotechnology. 2005, 2:180-194 LINK

J. Alcaraz, C.M. Nelson, M.J. Bissell. Biomechanical Approaches For Studying Integration of Tissue Structure and Function In Mammary Epithelia. J Mammary Gland Biol Neoplasia. 2004, 9:361-374 LINK

J. Alcaraz, L. Buscemi, X. Trepat, M. Grabulosa, B. Fabry, R Farré, D. Navajas. Microrheology of cultured lung epithelial cells measured with Atomic Force Microscopy. Biophys J. 2003, 84:2071-79 LINK

J. Alcaraz, L. Buscemi, M. Puig-de-Morales, J. Colchero, A. Baró, D. Navajas. Correction of Microrheological Measurements of Soft Samples with Atomic Force Microscopy for the hydrodynamic Drag on the Cantilever. Langmuir. 2002, 18: 716-721 LINK

M. Puig-de-Morales, M. Grabulosa, J. Alcaraz, J. Mullol, G.N. Maksym, J.J. Fredberg, D. Navajas. Microrheology of cultured airway epithelial cells measured by magnetic twisting cytometry with frequency domain demodulation. J.Appl.Physiol. 2001, 91: 1152-1159 LINK

D. Navajas, J. Alcaraz, R. Peslin, J. Roca, R. Farré. Evaluation of a method for assessing respiratory mechanics during non-invasive ventilation. Eur. Respir. J. 2000, 16: 704-709 LINK

Book chapters

J. Alcaraz, P. Roca-Cusachs. Shape and Mechanical Cues Underlying Cellular Homeostasis in Soft Organs. Chapter of Cells, Forces and the Microenvironment (English). Coordinated by C. M. Cuerrier and A.E. Pelling. Published by Pan Stanford and World Scientiphic Publishing (US), 2015. ISBN: 978-981-4613-36-1 LINK

J. Alcaraz. Microscopía de Fuerza Atómica. Chapter of Técnicas en Histología y Biología celular (Spanish). Coordinated by L. Montuenga. Published by Elsevier (Spain), 2014, 2024. ISBN: 978-84-458-2520-4 LINK

J. Alcaraz. Introducción a las aplicaciones biofarmacológicas y biotecnológicas de la bioingeniería. Chapter of Biotecnología y Biofármacos. Módulo II (Spanish). Coordinated by J. Piulats. Published by Plan Nacional de Formación Continuada. Consejo General de Colegios Oficiales de Farmacéuticos (Spain). 2010. ISBN: 978-84-693-1789-1 Legal Deposit: M-20075-2010

UP

CURRENT AND PAST COLLABORATIONS WITH PHARMA and BIOENGINEERING COMPANIES

(* funded projects)

(+ drugs or reagents provided)

• Boheringer-Ingelheim Inc., Austria (*, +)

• Basilea Pharmaceutica, Switzerland (*, +)

• Artidis, Switzerland (*)

• Peptomyc, Spain (+)

• Alentis Therapeutics, Switzerland (*,+)

• Nordic Biosciences, Denmark (+)

• NextCure, US (+)

NEWS AND VIEWS ON OUR WORK

New recruitment mechanisms for cancer-associated fibroblasts in lung adenocarcinoma, 2023 LINK

Collagen as a novel diagnostic and prognostic biomarker independent of TNM in lung cancer, 2023 LINK

TIMP-1 as a new therapeutic target in lung adenocarcinoma, 2022 LINK

How smoking impact on TGF-b signaling in fibroblasts mediates resistance to multi-tyrosine kinase inhibitor Nintedanib in Lung Cancer (collaboration with Boehringer-Ingelheim, Austria), 2019 LINK

How fibroblasts modulate response to multi-tyrosine kinase inhibitor Nintedanib in Lung Cancer (collaboration with Boehringer-Ingelheim, Spain), 2015 LINK

Crowdfunding campaing: “New approaches in the fight against lung cancer”, 2014 LINK

Cover of the 12^th issue of the journal of the Royal Society of Chemistry iBiology displays an image from our iBiology 2011 paper LINK

Nomination of our EMBO J 2008 by the Faculty of 1000 Biology LINK

OUTREACH ACTIVITIES

· Online seminar at IBEC 2021

· TV interview on the international Lung Cancer day, 2022

· Interview on Animal Experimentation

· Contribution on a video about creativity in different disciplines

COLLABORATORS

· Ongoing long-term collaborations (in alphabetic order):

Oriol Casanovas, ICO-IDIBELL, Barcelona (Spain)

Cristina Fillat, IDIBPAS, Barcelona (Spain)

Luis Montuenga, CIMA, Pamplona (Spain)

Josep Ramírez, Hospital Clínic, Barcelona (Spain)

Noemi Reguart, IDIBAPS, Barcelona (Spain)

Luca Roz, Istituto Nazionale dei Tumori, Milano (Italy)

Derek Radisky, Mayo Clinic, Jacksonville FL (US)

Xavier Trepat, IBEC, Barcelona (Spain)

Josep Samitier, IBEC, Barcelona (Spain)

· Clinical & Biomedical Institutions

Functional Unit of Thoracic Tumors, Hospital Clínic, Barcelona (Spain)

Institute for Bioengineering of Catalonia (IBEC), Barcelona (Spain)

CIBERES

DONAR SUPORT RECERCA CÀNCER DE PULMÓ

SUPPORT LUNG CANCER RESEARCH

El nostre grup de recerca accepta aportacions voluntàries per ajudar a finançar la seva recerca en càncer de pulmó.

Per fer-ho, es prega contactar amb l’investigador principal del grup (Jordi Alcaraz) per email (jalcaraz@ub.edu) o telèfon (93 403 1148). Així mateix, podeu també contactar-nos per a qualsevol dubte o inquietud relacionada amb la nostra recerca!

Podeu contribuir amb qualsevol aportació o fent difusió de la nostra recerca.

Moltes gràcies!

-------------------------------------------------------------------------------------------------------------------------------

Our research group accepts volunteer donations to support our lung cancer research. For this purpose, please contact the principal investigator of this group (Jordi Alcaraz) by email (jalcaraz@ub.edu) or telephone (+3493 403 1148). Likewise, should you have any doubt or different request on our research, please contact us!

You can help us by making a donation or spreading the word of our research.

Many thanks!

TEACHING

We are actively involved in the following academic programs:

· Degree in Medicine, UB

· Degree in Molecular Medicine, UB

· Degree in Biomedical Engineering, UB

· Master in Biomedicine, UB

OPENINGS FOR MASTER STUDENTS, GRAD STUDENTS AND POSTDOCS

Our group is continuously open to students at the level of Master, Graduate (PhD) and Postdoctoral level. Please contact us to inquire about currently available positions and projects.