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Fernando Calvo González (IP)

  • IBBTEC. C/ Albert Einstein 22, PCTCAN, 39011 Santander
  • (+34) 942 206825
  • calvof@unican.es
  • Tumour Microenvironment
  • Principal Investigator
  • Cancer
  • Department of Cell & Molecular Signalling

Fernando got a BSc in Biochemistry at the Universidad del Pais Vasco (2001). Following a year at AstraZeneca (Manchester, UK), he joined the group of Piero Crespo at CSIC/Universidad de Cantabria (Santander, Spain), where he obtained a PhD studying Ras GTPases in 2008. He then carried out post-doctoral work in London (Erik Sahai) where he studied cancer metastasis and the tumour microenvironment. In 2013 he set up his own group at The Institute of Cancer Research (London, UK). In 2018 he obtained a Ramón y Cajal Fellowship and returned to Santander, where he leads the Tumour Microenvironment Team at the IBBTEC. In 2021 he was promoted to CSIC Científico Titular (tenured Scientific Head) at IBBTEC. Fernando's group uses a wide range of techniques from conventional cell and molecular biology, through in vivo models and analysis of clinical material, to study the role of the tumour microenvironment in cancer progression, dissemination and response to therapy.

 

Dr. Calvo has authored more than 30 peer-reviewed publications in SCI journals, including Nature Cell Biology, Nature Communications, Journal of Cell Biology y Journal of National Cancer Institute. Throughout his career he has been regularly funded by national and international grants, including ERC-CoG, Lab AECC, Worldwide Cancer Research Grant, CRUK Multidiciplinary Award and several National Research Grants. He has mentored 1 doctoral and 2 master theses (plus several ongoing) and he has been honoured by different national and international research awards. He acts as a reviewer for numerous scientific journals and granting agencies. He has been invited as a speaker to more than 40 meetings, workshops and seminar series in national and international universities and scientific institutions.


​​​Tumour Microenvironment


Research lines

  • Non-cancerous cells and matricellular molecules within the tumour, collectively defined as the tumour microenvironment, participate in many hallmarks of cancer. The Tumour Microenvironment Team investigates the multicellular context of solid tumours to understand the molecular mechanisms regulating cancer progression and dissemination. The ultimate goal of these studies is to yield important insights into cancer biology leading to improved strategies for cancer therapy. To achieve this, we collaborate with academics, clinicians and engineers in a multidisciplinary approach, integrating experimental cancer models, murine and patient-derived material, complex in vitro and in silico systems and high throughput genomics and bioinformatics. 

  • Cytoskeletal regulators of cancer dissemination. Our team is interested in understanding why and how cancer cells spread through the body. Using state-of-the-art in vitro approaches and pre-clinical models, we study the reciprocal interactions between invading/metastatic cells and their microenvironment, and the molecular rearrangements that promote efficient metastatic behaviours in cancer cells, with a particular emphasis in the modulation of the cytoskeleton.

  • Mechanisms of stromal reprogramming in cancer. We investigate the environmental cues (chemical or physical) and signals from malignant cells that lead to the emergence of tumour-promoting phenotypes in otherwise normal cells of the tumour microenvironment, with a particular focus in cancer-associated fibroblasts (CAF). Using molecular and bioinformatics tools, we examine patterns of gene expression and signal activation in cancer stroma. We then investigate the effect of reciprocal interactions between cancer cells and normal cells in these patterns, their relevance in tumoural processes and strategies to perturb them to deter tumour progression.

  • Characterisation of the role of CAF heterogeneity in tumour progression. We have developed in vitro and in vivo systems to investigate CAF behaviour, their contribution to the hallmarks of cancer (e.g. cancer cell growth, invasion, angiogenesis, immune suppression), and the molecular mechanisms controlling them. However, there is molecular and functional heterogeneity within the CAF population, which has a major impact in tumour evolution and therapeutic response. Our team aims at examining this diversity and its contribution to metastatic dissemination and resistance.  

Funding 


  • “Harnessing Stromal Fibroblasts to Reduce Resistance and Improve Colon Cancer Therapeutics” | ERC Consolidator Grant 2021 (101045756) | 2022-2027 | IP: Fernando Calvo.
  • “Microscopy platform with super-resolution and high content analysis (HCA) capabilities” | MINECO – Infrastructure and Equipment Call (EQC2021-007003-P) | IPs: Ignacio Varela, Piero Crespo, Maria Angeles Ros, Fernando Calvo, Juan Carlos Acosta. 
  • ​"Silencing the pro-tumor crosstalk between cancer-associated fibroblasts and the tumor microenvironment in colorectal cancer” | Proyectos de Generacion de Conocimiento (PID2021-128107OB-I00) | 2022-2025 | IP: Fernando Calvo.​​​
  •  “Multidisciplinary dissection of the chemotherapy resistance mechanisms in triple negative breast cancer: A step towards improved clinical care” | AECC – Coordinated Projects 2021 (PRYCO211372RODR) | 2021-2025 | IPs: Angel Nebreda, Ignacio Varela, Juan Miguel Cejalvo, and Fernando Calvo. 
  • "Targeting cancer-associated fibroblasts using HDAC inhibitors to improve therapies for breast, ovarian and colon cancers" | LAB AECC 2019 (LABAE19044CALV)| 2020-2023 | PI: Fernando Calvo
  • "Cortocircuitar el microambiente tumoral para entorpecer el desarrollo de cánceres agresivos" | BBVA Leonardo Awards 2019 (IN[19]_BBM_BAS_0076) | 2019-2021 | IP: Fernando Calvo
  • "Identification and characterization of strategies to modulate cancer-associated fibroblasts to deter tumour progression (STOPCAF)" | Proyectos de I+D+i RETOS INVESTIGACIÓN-MINECO - RTI2018-096778-A-I00 | 2019-2021 | PI: Fernando Calvo.
  • Ramon y Cajal Research Fellowship | Spanish Ministry of Economy and Competitiveness (RYC-2016-20352) | 2018-2021 | PI: Fernando Calvo.
  • Contrato Ramón y Cajal | Ministerio de Ciencia, Innovación y Universidades (RYC-2016-20352) | 2018-2023 | PI: Fernando Calvo.
  • Collaborative Agreement The Institute of Cancer Research - CSIC | The Institute of Cancer Research, UK | 2018-2020 | IP: Fernando Calvo.
  • "Investigating the physical and biological determinants of cancer cell extravasation" | Multidisciplinary Project Award (C57744-A2367) | Cancer Research UK | IPs: Fernando Calvo y Emad Moeendarbary (Imperial College London, UK) | 2017-2021.  
  • "Investigating the role of stromal Dkk3 in breast cancer progression and metastasis" | Worldwide Cancer Research (Ref 15-0273) | 2015-2018 | IP: Fernando Calvo. 
  • "Functional characterization of breast cancer-associated fibroblasts" | CRUK Postdoctoral Fellowship | Cancer Research UK | 2010-2013 | IP: Erik Sahai.


Studentships to my team


  • “Mechanical Regulation of CAF epigenome” | Ignacio Marina (internship) | CSIC – JAE-Intro at IBBTEC, Spain | 2021-2022. 
  •  “Role of stromal HSF1 in tumour progression by cancer-associated fibroblasts” | Beatriz Rodríguez | Universidad de Cantabria – PhD Studentship at IBBTEC, Spain | 2021-2025.  
  • “Investigating the crosstalk between CAFs and macrophages in cancer” | David García (internship) | CSIC – JAE-Intro at IBBTEC, Spain | 2020-2021. 
  •  “Epigenetic reprogramming of CAFs” | María Subijana (PhD) | Proyectos de I+D+i RETOS INVESTIGACIÓN-MINECO – FPI/PhD Studentship  at IBBTEC, Spain | 2020-2024. 
  • “Investigating the role of stromal HSP90 in shaping aggressive tumour microenvironments” | Silvia Dominguez (PhD) | AECC-Cantabria at IBBTEC, Spain | 2020-2023. 
  • “Role of HSP90 in tumour progression by cancer-associated fibroblasts” | Guillermo Iborra (PhD) | Universidad de Cantabria – IBBTEC, Spain | 2019-2022 | Granted – the candidate turned it down for personal reasons. 
  • "Investigating the role of stromal IGFBP5 in breast cancer progression, dissemination and therapeutic resistance" | Maria Semiannikova | The Institute of Cancer Research, UK | 2017-2021. 
  • "Role of Borg proteins in cancer cell invasion and metastasis" | Aaron Farrugia (PhD) | The Institute of Cancer Research, UK | 2014-2018.





CAFs vs. TECs: when blood feuds fuel cancer progression, dissemination and therapeutic resistance

CAFs vs. TECs: when blood feuds fuel cancer progression, dissemination and therapeutic resistance

Coursier D, Calvo F.

​​​​​​​​Cell Oncol. 2024 Mar 7. Online ahead of print.​​



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CD73 controls Myosin II-driven invasion, metastasis, and immunosuppression in amoeboid pancreatic cancer cells

CD73 controls Myosin II-driven invasion, metastasis, and immunosuppression in amoeboid pancreatic cancer cells

Samain R, Maiques O, Monger J, Lam H, Candido J, George S, Ferrari N, KohIhammer L, Lunetto S, Varela A, Orgaz JL, Vilardell F, Olsina JJ, Matias-Guiu X, Sarker D, Biddle A, Balkwill FR, Eyles J, Wilkinson RW, Kocher HM, Calvo F, Wells CM, Sanz-Moreno V.


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Stromal cells regulate mechanics of tumour spheroid

Stromal cells regulate mechanics of tumour spheroid

Agrawal A, Lasli S, Javanmardi Y, Coursier D, Micalet A, Watson S, Shahreza S, Serwinski B, Djordjevic B, Szita N, Cheema U, Bertazzo S, Calvo F, Moeendarbary E.

​Mater Today Bio. 2023 Oct 6:23:100821

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Emergent mechanical control of vascular morphogenesis

Emergent mechanical control of vascular morphogenesis

Whisler J, Shahreza S, Schlegelmilch K, Ege N, Javanmardi Y, Malandrino A, Agrawal A, Fantin A, Serwinski B, Azizgolshani H, Park C, Shone V, Demuren OO, Del Rosario A, Butty VL, Holroyd N, Domart MC, Hooper S, Szita N, Boyer LA, Walker-Samuel S, Djordjev

​Sci Adv. 2023 Aug 11;9(32):eadg9781.

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Endothelium and Subendothelial Matrix Mechanics Modulate Cancer Cell Transendothelial Migration.

Endothelium and Subendothelial Matrix Mechanics Modulate Cancer Cell Transendothelial Migration.

Javanmardi Y, Agrawal A, Malandrino A, Lasli S, Chen M, Shahreza S, Serwinski B, Cammoun L, Li R, Jorfi M, Djordjevic B, Szita N, Spill F, Bertazzo S, Sheridan GK, Shenoy V, Calvo F, Kamm R, Moeendarbary E

Adv Sci (Weinh). 2023 Apr 13:e2206554​
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Dissecting the functions of cancer-associated fibroblasts to therapeutically target head and neck cancer microenvironment

Dissecting the functions of cancer-associated fibroblasts to therapeutically target head and neck cancer microenvironment

Prieto-Fernández L, Montoro-Jiménez I, de Luxan-Delgado B, Otero-Rosales M, Rodrigo JP, Calvo F, García-Pedrero JM, Álvarez-Teijeiro S

​Biomed Pharmacother. 2023 May;161:114502​​

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Driving role of head and neck cancer cell secretome on the invasion of stromal fibroblasts: Mechanistic insights by phosphoproteomics

Driving role of head and neck cancer cell secretome on the invasion of stromal fibroblasts: Mechanistic insights by phosphoproteomics

Prieto-Fernandez L, Villaronga MLA, Hermida-Prado F, Hijazi M, Montoro-Jimenez I, Pevida M, Llames S, Rodrigo JP, Cutillas P, Calvo F, Garcia-Pedrero JM, Alvarez-Teijeiro S

​Pharmacother. 2023 Feb;158:114176

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Stromal oncostatin M cytokine promotes breast cancer progression by reprogramming the tumor microenvironmentStromal oncostatin M cytokine promotes breast cancer progression by reprogramming the tumor microenvironment

Stromal oncostatin M cytokine promotes breast cancer progression by reprogramming the tumor microenvironmentStromal oncostatin M cytokine promotes breast cancer progression by reprogramming the tumor microenvironment

Araujo AM, Abaurrea A, Azcoaga P et al.

​J Clin Invest. 2022 Apr 1;132(7):e148667.

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CDC42EP5/BORG3 modulates SEPT9 to promote actomyosin function, migration, and invasion

CDC42EP5/BORG3 modulates SEPT9 to promote actomyosin function, migration, and invasion

Aaron J. Farrugia, Javier Rodríguez, Jose L. Orgaz, María Lucas, Victoria Sanz-Moreno, Fernando Calvo

​J Cell Biol (2020) 219 (9): e201912159. https://doi.org/10.1083/jcb.201912159. Epub 2020 Aug 14

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Genomic and transcriptomic determinants of therapy resistance and immune landscape evolution during anti-EGFR treatment in colorectal cancer.

Genomic and transcriptomic determinants of therapy resistance and immune landscape evolution during anti-EGFR treatment in colorectal cancer.

Woolston A, Khan K, Spain G, Barber L, Griffiths B, Gonzalez Exposito R, Patil Y, Punta M, Mansukhani S, Davies M, Furness A, Sclafani F, Peckitt C, Kouvelakis K, Ranftl R, Begum R, Rana I, Thomas J, Bryant A, Quezada S, Wotherspoon A, Khan N, Lise S, Fot

Cancer Cell 36, 35-50. 

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SREBP1 drives Keratin-80-dependent cytoskeletal changes and invasive behavior in endocrine-resistant ERα breast cancer

SREBP1 drives Keratin-80-dependent cytoskeletal changes and invasive behavior in endocrine-resistant ERα breast cancer

Ylenia Perone, Aaron J. Farrugia, Alba Rodríguez Meira, Balázs Győrffy, Charlotte Ion, Andrea Uggetti, Antonios Chronopoulos, Pasquale Marrazzo, Monica Faronato, Sami Shousha, Claire Davies, Jennifer H. Steel, Naina Patel, Armando del Rio Hernandez, Charl

​Nature Communicationsvolume 10, Article number: 2115 (2019)

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An Integrated Global Analysis of Compartmentalized HRAS Signaling.

An Integrated Global Analysis of Compartmentalized HRAS Signaling.

Santra T, Herrero A, Rodriguez J, von Kriegsheim A, Iglesias-Martinez LF, Schwarzl T, Higgins D, Aye TT, Heck AJR, Calvo F, Agudo-Ibáñez L, Crespo P, Matallanas D, Kolch W.

​Cell Rep. 2019 Mar 12;26(11):3100-3115.e7. doi: 10.1016/j.celrep.2019.02.038.

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Dickkopf-3 links HSF1 and YAP/TAZ signalling to control aggressive behaviours in cancer-associated fibroblasts

Ferrari N, Ranftl R, Chicherova I, Slaven ND, Moeendarbary E, Farrugia AJ, Lam M, Semiannikova M, Westergaard MCW, Tchou J, Magnani L, Calvo F*

​Nature Communications 2019, Jan 10; 10:130

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Factors secreted by cancer-associated fibroblasts that sustain cancer stem properties in head and neck squamous carcinoma cells as potential therapeutic targets

Álvarez-Teijeiro S, García-Inclán S, Villaronga MA, Casado P, Hermida-Prado F, Granda-Díaz R, Rodrigo JP, Calvo F, del Rio-Ibisate N, Gandarillas A, Morís F, Hermsen M, Cutillas P, García-Pedrero JM

​Cancers 10(9), 334. 

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Regulation of mechanotransduction: emerging roles for Septins

Lam M and Calvo F*

​Cytoskeleton. Aug 9. doi: 10.1002/cm.21485. 

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Characterisation of HRAS local signal transduction networks using engineered site-specific exchange factors

Herrero A, Reis-Cardoso M, Jimenez-Gomez I, Doherty C, Agudo Ibanez L, Pinto A, Calvo F, Kolch W, Crespo P, Matallanas DG

​Small GTPases Nov 26:1-13. 

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Analysis of breast cancer cell invasion using an organotypic culture system

Ranftl R and Calvo F*

​Methods in Molecular Biology 1612:199-212.

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Cdc42 regulates Cdc42EP3 function in Cancer-Associated Fibroblasts

Farrugia AJ and Calvo F*

​Small GTPases Jan 2;8(1):49-57. 

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The Borg family of Cdc42 effector proteins Cdc42EP1-5

Farrugia AJ and Calvo F*

​Biochemical Society Transactions. Dec 02,44 (6) 1709-1716. 

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Cdc42EP3/BORG2 and septin network enables mechano-transduction and the emergence of cancer-associated fibroblasts

Calvo F*, Ranftl R, Hooper S, Farrugia AJ, Moeendarbary E, Bruckbauer A, Batista F, Charras G and Sahai E*

​Cell Reports13(12):2699-714. 

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Tumour cell-derived Wnt7a recruits and activates fibroblasts to promote tumour aggressiveness

Avgustinova A, Iravani M, Robertson D, Fearns A, Gao Q, Klingbeil P, Hanby AM, Speirs V, Sahai E, Calvo F, and Isacke CM

​Nature CommunicationsJan 18; 7:10305.

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Mesenchymal Cancer Cell-Stroma Crosstalk Promotes Niche Activation, Epithelial Reversion, and Metastatic Colonization.

Del Pozo-Martin Y, Park D, Ramachandran A, Ombrato L, Calvo F, Chakravarty P, Spencer-Dene B, Derzsi S, Hill CS, Sahai E and Malanchi I

​Cell Reports 13(11):2456-69. 

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Reactivation of p53 by a Cytoskeletal Sensor to Control the Balance Between DNA Damage and Tumor Dissemination

Herraiz C, Calvo F, Pandya P, Cantelli G, Rodriguez-Hernandez I, Orgaz JL, Kang N, Chu T, Sahai E, Sanz-Moreno V

​Journal of National Cancer Institute. 108(1): djv289. 

https://doi.org/10.1093/jnci/djv289

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TGFβ suppresses CD248 expression in non-cancer cells via canonical Smad-dependent signaling pathways

Suresh S, Valdez Y, Xu A, O’Byrne A, Calvo F, Lei V and Conway EM.

​BMC Cancer 14(1):113. 

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Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer associated fibroblasts

Calvo F, Ege N, Grande-Garcia A, Hooper S, Jenkins RP, Chaudhry S, Harrington K, Williamson P, Moeendarbary E, Charras G and Sahai E.

​Nature Cell Biology 15: 637-646. 

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Cell communication networks in cancer invasion

Calvo F and Sahai S.

​Current Opinions in Cell Biology. 23:1–9..

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Ras and Rho GTPases on the move: The RasGRF connection.

Crespo P, Calvo F, Sanz-Moreno V. Bioarchitecture. 2011 Jul;1(4):200-204.

​[PubMed]

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Ras GEFs as inhibitors of Rho GTPases: RasGRF suppresses Cdc42-mediated tumor cell movement, cytoskeletal dynamics and transformation.

Calvo F., Sanz-Moreno V, Agudo-Ibáñez L., Wallberg F., Sahai E., Marshall C.J., and Crespo P. Nat. Cell Biol. 13, 819-826. (2011). (Seleccionado por The Faculty of 1000).

​[pubmed]

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An actor on many stages: Ras subcellular localization, site-specific regulation and functions

Arozarena I., Calvo F., Agudo-Ibañez L. and Crespo P. Genes & Cancer. 182-194. (2011).

​[pubmed]

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RasGRF negatively regulates Cdc42-mediated transformation, cytoskeletal dynamics and tumor cell movement

Calvo F, Sanz-Moreno V, Agudo-Ibáñez L, Wallberg F, Sahai E, Marshall CJ and Crespo P.

​Nature Cell Biology13(7):819-26. 

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ERK1/2 MAP kinases promote cell cycle entry by rapid, kinase-independent disruption of Retinoblastoma–LaminA complexes.

Rodríguez J., Calvo F., González J.M., Casar B., Andrés V. and Crespo P. J. Cell Biol. 191, 967-979. (2010). (Editorial en el mismo número; Editorial en Science Sig. 3, ec371 2010; Seleccionado por The Faculty of 1000).

​[pubmed]

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The Ras-ERK pathway: understanding site-specific signaling provides hope of new anti-tumour therapies

Calvo F., Agudo-Ibáñez L., and Crespo P. Bioessays. 32, 412-421. (2010).

​[pubmed]

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Patricia Carnicero Jiménez

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Diane Coursier

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Silvia Domínguez García

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Miguel Juliá Molina

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Francesca Nonatelli

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Carmen Pérez López

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Javier Rodríguez Martínez

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Beatriz Rodríguez Ortiz

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María Subijana Fernandez de Larrinoa

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IBBTEC

Instituto de Biomedicina y Biotecnología de Cantabria.
PCTCAN - Cl. Albert Einstein, 22
39011 Santander

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