Imperial College London

DrArmandoDel Rio Hernandez

Faculty of EngineeringDepartment of Bioengineering

Senior Lecturer
 
 
 
//

Contact

 

+44 (0)20 7594 5187a.del-rio-hernandez

 
 
//

Location

 

308Bessemer BuildingSouth Kensington Campus

//

Summary

 

Publications

Publication Type
Year
to

31 results found

Chronopoulos A, Lieberthal TJ, del Río Hernández AE, 2017, Pancreatic cancer: a mechanobiology approach, Convergent Science Physical Oncology, Vol: 3, Pages: 013001-013001

JOURNAL ARTICLE

Chronopoulos A, Lieberthal TJ, del Río Hernández AE, 2017, Exosomes as a platform for ‘liquid biopsy’ in pancreatic cancer, Convergent Science Physical Oncology, Vol: 3, Pages: 013005-013005

JOURNAL ARTICLE

Inostroza-Brito KE, Collin EC, Majkowska A, Elsharkawy S, Rice A, Hernandez AEDR, Xiao X, Rodriguez-Cabello J, Mata Aet al., 2017, Cross-linking of a biopolymer-peptide co-assembling system, ACTA BIOMATERIALIA, Vol: 58, Pages: 80-89, ISSN: 1742-7061

JOURNAL ARTICLE

Lachowski D, Cortes E, Pink D, Chronopoulos A, Karim SA, Morton JP, Hernandez AEDRet al., 2017, Substrate rigidity controls activation and durotaxis in pancreatic stellate cells, Scientific Reports, Vol: 7, ISSN: 2045-2322

Pancreatic Ductal Adenocarcinoma (PDAC) is an aggressive malignancy characterised by the presence of extensive desmoplasia, thought to be responsible for the poor response of patients to systemic therapies. Pancreatic stellate cells (PSCs) are key mediators in the production of this fibrotic stroma, upon activation transitioning to a myofibroblast-like, high matrix secreting phenotype. Given their importance in disease progression, characterisation of PSC activation has been extensive, however one aspect that has been overlooked is the mechano-sensing properties of the cell. Here, through the use of a physiomimetic system that recapitulates the mechanical microenvironment found within healthy and fibrotic pancreas, we demonstrate that matrix stiffness regulates activation and mechanotaxis in PSCs. We show the ability of PSCs to undergo phenotypic transition solely as a result of changes in extracellular matrix stiffness, whilst observing the ability of PSCs to durotactically respond to stiffness variations within their local environment. Our findings implicate the mechanical microenvironment as a potent contributor to PDAC progression and survival via induction of PSC activation and fibrosis, suggesting that direct mechanical reprogramming of PSCs may be a viable alternative in the treatment of this lethal disease.

JOURNAL ARTICLE

Lachowski D, Cortes E, Robinson B, Rice A, Rombouts K, Del Río Hernández AEet al., 2017, FAK controls the mechanical activation of YAP, a transcriptional regulator required for durotaxis., FASEB J

Focal adhesion kinase (FAK) is a key molecule in focal adhesions and regulates fundamental processes in cells such as growth, survival, and migration. FAK is one of the first molecules recruited to focal adhesions in response to external mechanical stimuli and therefore is a pivotal mediator of cell mechanosignaling, and relays these stimuli to other mechanotransducers within the cytoplasm. Yes-associated protein (YAP) has been identified recently as one of these core mechanotransducers. YAP translocates to the nucleus following changes in cell mechanics to promote the expression of genes implicated in motility, apoptosis, proliferation, and organ growth. Here, we show that FAK controls the nuclear translocation and activation of YAP in response to mechanical activation and submit that the YAP-dependent process of durotaxis requires a cell with an asymmetric distribution of active and inactive FAK molecules.-Lachowski, D., Cortes, E., Robinson, B., Rice, A., Rombouts, K., Del Río Hernández, A. E. FAK controls the mechanical activation of YAP, a transcriptional regulator required for durotaxis.

JOURNAL ARTICLE

Rice AJ, Cortes E, Lachowski D, Cheung BCH, Karim SA, Morton JP, Del Río Hernández Aet al., 2017, Matrix stiffness induces epithelial-mesenchymal transition and promotes chemoresistance in pancreatic cancer cells, Oncogenesis, Vol: 6, Pages: e352-e352, ISSN: 2157-9024

Increased matrix rigidity associated with the fibrotic reaction is documented to stimulate intracellular signalling pathways that promote cancer cell survival and tumour growth. Pancreatic cancer is one of the stiffest of all human solid carcinomas and is characterised by a remarkable desmoplastic reaction. Here we use mouse models, genetically engineered to recapitulate human pancreatic cancer, and several pancreatic cancer cell lines as a model to investigate the effect of matrix stiffness in epithelial-mesenchymal transition (EMT) and resistance to chemotherapeutics. We found that recapitulation of the fibrotic rigidities found in pancreatic cancer tissues promote elements of EMT, including increases in vimentin expression, decreases in E-cadherin expression, nuclear localisation of β-catenin, YAP and TAZ and changes in cell shape towards a mesenchymal phenotype. We also report that stiffness induces chemoresistance to paclitaxel, but not to gemcitabine, both commonly used therapeutics, suggesting that environmental rigidity underlies an aspect of chemoresistance.

JOURNAL ARTICLE

Attwood SJ, Cortes E, Haining AWM, Robinson B, Li D, Gautrot J, Hernandez ADRet al., 2016, Adhesive ligand tether length affects the size and length of focal adhesions and influences cell spreading and attachment, SCIENTIFIC REPORTS, Vol: 6, ISSN: 2045-2322

JOURNAL ARTICLE

Chronopoulos A, Robinson B, Sarper M, Cortes E, Auernheimer V, Lachowski D, Attwood S, Garcia R, Ghassemi S, Fabry B, Hernandez ADRet al., 2016, ATRA mechanically reprograms pancreatic stellate cells to suppress matrix remodelling and inhibit cancer cell invasion, NATURE COMMUNICATIONS, Vol: 7, ISSN: 2041-1723

JOURNAL ARTICLE

Haining AWM, Lieberthal TJ, Hernandez ADR, 2016, Talin: a mechanosensitive molecule in health and disease, FASEB JOURNAL, Vol: 30, Pages: 2073-2085, ISSN: 0892-6638

JOURNAL ARTICLE

Haining AWM, von Essen M, Attwood SJ, Hytönen VP, del Río Hernández Aet al., 2016, All Subdomains of the Talin Rod Are Mechanically Vulnerable and May Contribute To Cellular Mechanosensing, ACS Nano, Vol: 10, Pages: 6648-6658, ISSN: 1936-0851

JOURNAL ARTICLE

Kis Z, Rodin T, Zafar A, Lai Z, Freke G, Fleck O, Hernandez ADR, Towhidi L, Pedrigi RM, Homma T, Krams Ret al., 2016, Development of a synthetic gene network to modulate gene expression by mechanical forces, SCIENTIFIC REPORTS, Vol: 6, ISSN: 2045-2322

JOURNAL ARTICLE

Lachowski D, Cortes E, Robinson B, Rombouts K, Hernandez ADRet al., 2016, ELUCIDATING THE BIOMECHANICAL RESPONSE OF HUMAN HEPATIC STELLATE CELLS ON SUBSTRATES MIMICKING HEALTHY AND FIBROTIC MATRIX RIGIDITY, JOURNAL OF HEPATOLOGY, Vol: 64, Pages: S706-S706, ISSN: 0168-8278

JOURNAL ARTICLE

Robinson BK, Cortes E, Rice AJ, Sarper M, Hernandez ADRet al., 2016, Quantitative analysis of 3D extracellular matrix remodelling by pancreatic stellate cells, BIOLOGY OPEN, Vol: 5, Pages: 875-882, ISSN: 2046-6390

JOURNAL ARTICLE

Sarper M, Cortes E, Lieberthal T, del Rio Hernandez Aet al., 2016, ATRA modulates mechanical activation of TGF-β by pancreatic stellate cells, Scientific Reports, Vol: 6, ISSN: 2045-2322

The hallmark of pancreatic ductal adenocarcinoma (PDAC) is abundant desmoplasia, which is orchestrated by pancreatic stellate cells (PSCs) and accounts for the majority of the stroma surrounding the tumour. Healthy PSCs are quiescent, but upon activation during disease progression, they adopt a myofibroblast-contractile phenotype and secrete and concomitantly reorganise the stiff extracellular matrix (ECM). Transforming growth factor β (TGF-β) is a potent activator of PSCs, and its activation requires spatiotemporal organisation of cellular and extracellular cues to liberate it from an inactive complex with latent TGF-β binding protein (LTBP). Here we study the mechanical activation of TGF-β by PSCs in vitro by investigating LTBP-1 organisation with fibrillar fibronectin and show that all trans-retinoic acid (ATRA), which induces PSC quiescence, down-regulates the ability of PSCs to mechanically organise LTBP-1 and activate TGF-β through a mechanism involving myosin II dependent contractility. Therefore, ATRA inhibits the ability of PSCs to mechanically release active TGF-β, which might otherwise act in an autocrine manner to sustain PSCs in an active state and a tumour-favouring stiff microenvironment.

JOURNAL ARTICLE

Roca-Cusachs P, del Rio A, Puklin-Faucher E, Gauthier NC, Biais N, Sheetz MPet al., 2013, Integrin-dependent force transmission to the extracellular matrix by alpha-actinin triggers adhesion maturation, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 110, Pages: E1361-E1370, ISSN: 0027-8424

JOURNAL ARTICLE

Roca-Cusachs P, Gauthier NC, del Rio A, Sheetz MPet al., 2009, Clustering of alpha(5)beta(1) integrins determines adhesion strength whereas alpha(v)beta(3) and talin enable mechanotransduction, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 106, Pages: 16245-16250, ISSN: 0027-8424

JOURNAL ARTICLE

del Rio A, Perez-Jimenez R, Liu R, Roca-Cusachs P, Fernandez JM, Sheetz MPet al., 2009, Stretching Single Talin Rod Molecules Activates Vinculin Binding, SCIENCE, Vol: 323, Pages: 638-641, ISSN: 0036-8075

JOURNAL ARTICLE

Del Rio A, Dutta K, Chavez J, Ubarretxena-Belandia I, Ghose Ret al., 2007, Solution structure and dynamics of the N-terminal cytosolic domain of rhomboid intramembrane protease from Pseudomonas aeruginosa: Insights into a functional role in intramembrane proteolysis, JOURNAL OF MOLECULAR BIOLOGY, Vol: 365, Pages: 109-122, ISSN: 0022-2836

JOURNAL ARTICLE

Del Rio A, Anand A, Ghose R, 2006, Detection of correlated dynamics on multiple timescales by measurement of the differential relaxation of zero- and double-quantum coherences involving sidechain methyl groups in proteins, JOURNAL OF MAGNETIC RESONANCE, Vol: 180, Pages: 1-17, ISSN: 1090-7807

JOURNAL ARTICLE

del Rio A, Coto B, Renuncio JAR, Pando Cet al., 2004, Vapor-liquid equilibria for the binary system 2,2-dimethylbutane plus 1,1-dimethylpropyl methyl ether (TAME) at 298.15, 318.15, and 338.15 K, FLUID PHASE EQUILIBRIA, Vol: 221, Pages: 1-6, ISSN: 0378-3812

JOURNAL ARTICLE

Segade L, de Llano JJ, Jimenez E, del Rio A, Pando C, Renuncio JARet al., 2003, Vapor-liquid equilibria of propan-1-ol+1,1-dimethylethyl methyl ether (MTBE) mixtures. Experimental results and modeling, PHYSICAL CHEMISTRY CHEMICAL PHYSICS, Vol: 5, Pages: 2858-2861, ISSN: 1463-9076

JOURNAL ARTICLE

Spuhl O, Arlt W, Hernandez AD, 2003, Prediction of thermodynamic material properties with the COSMO-RS continuum model, Meeting of the GVC Specialized committee on Thermal Dismantling of Gas, Publisher: WILEY-V C H VERLAG GMBH, Pages: 58-62, ISSN: 0009-286X

CONFERENCE PAPER

de Llano JJ, Segade L, Jimenez E, del Rio A, Renuncio JAR, Pando Cet al., 2003, Vapor-liquid equilibria for the binary system hexan-1-ol plus tert-butyl methyl ether (MTBE) at 298.15, 318.15, and 338.15 K, FLUID PHASE EQUILIBRIA, Vol: 208, Pages: 115-121, ISSN: 0378-3812

JOURNAL ARTICLE

del Rio A, Coto B, Pando C, Renuncio JARet al., 2002, Vapor-liquid equilibria for the binary system hexane+1,1-dimethylpropyl methyl ether at 298.15, 308.15, 318.15, and 328.15 K, INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH, Vol: 41, Pages: 1364-1369, ISSN: 0888-5885

JOURNAL ARTICLE

del Rio A, Coto B, Pando C, Renuncio JARet al., 2002, Vapor-liquid equilibria and excess properties of octane+1,1-dimethylpropyl methyl ether (TAME) mixtures, FLUID PHASE EQUILIBRIA, Vol: 200, Pages: 41-51, ISSN: 0378-3812

JOURNAL ARTICLE

del Rio A, Coto B, Pando C, Renuncio JARet al., 2001, Vapor-liquid equilibria and excess properties of cyclohexane-1,1-dimethylpropyl methyl ether (TAME) mixtures, INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH, Vol: 40, Pages: 689-695, ISSN: 0888-5885

JOURNAL ARTICLE

del Rio A, Coto B, Pando C, Renuncio JARet al., 2001, Vapor-liquid equilibria for the binary systems decane+1, 1-dimethylethyl methyl ether (MTBE) and decane+1, 1-dimethylpropyl methyl ether (TAME) at 308.15, 318.15 and 328.15 K, FLUID PHASE EQUILIBRIA, Vol: 187, Pages: 299-310, ISSN: 0378-3812

JOURNAL ARTICLE

del Rio A, Coto R, Pando C, Renuncio JARet al., 1999, Vapour-liquid equilibria for the binary system cyclohexane-1,1-dimethylethyl methyl ether (MTBE) at 298.15, 308.15 and 318.15 K, PHYSICAL CHEMISTRY CHEMICAL PHYSICS, Vol: 1, Pages: 4995-4998, ISSN: 1463-9076

JOURNAL ARTICLE

Robinson B, Rice A, Cortes E, Del Rio Hernandez AEet al., Assessment of extracellular matrix remodeling using 3D Matrigel/collagen matrices and second harmonic generation microscopy, Jove-Journal of Visualized Experiments, ISSN: 1940-087X

JOURNAL ARTICLE

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

Request URL: http://wlsprd.imperial.ac.uk:80/respub/WEB-INF/jsp/search-html.jsp Request URI: /respub/WEB-INF/jsp/search-html.jsp Query String: respub-action=search.html&id=00780172&limit=30&person=true