Research

Rho GTPases are molecular switches that control the cytoskeleton. Deregulation of Rho GTPases can result in aberrant function and disease, including cancer. The spreading of cancer cells from one part of the body to another, called metastasis, is one of the biggest causes of cancer death. The other major challenge in the clinic is drug resistance. In our lab we are studying how Rho GTPase signalling and cytoskeletal remodelling can control many processes: invasion and metastasis, tumour promoting inflammation and drug responses. We are particularly interested in understanding how cancer cells sense extracellular signals via their cytoskeleton and integrate the responses altering transcription. On the other hand, how cancer cells interact with the tumour microenvironment is crucial for tumour progression and dissemination. We aim to understand how this communication is controlled by the cytoskeleton of cancer cells.

The lab combines 'OMICs', molecular biology, microscopy in 3D matrices, co-culture systems, animal models and digital pathology in patient tissues to identify molecular determinants driven by Rho GTPase signalling that drive cancer progression and metastatic potential. Our ultimate goal is to define if manipulations in the cytoskeleton of cancer cells will lead to improved efficacy of current therapeutic approaches.

Other Activities

• 2018-present Member of The British Association for Cancer Research (BACR)
• 2017-present Member of The British Society for Cell Biology (BSCB)
• 2013-present Member of The Women of Influence Group, by Cancer Research UK

Major Funding

• 2018-2020- Barts Charity
• 2017-2022- Cancer Research UK Senior Fellowship “Investigating Rho-kinase (ROCK) in melanoma progression and therapy response”
• 2017-2019- The Harry J. Lloyd Charitable Trust “Understanding how cytoskeletal remodelling leads to drug resistance in melanoma”

Recent Publications

Myosin II Reactivation and Cytoskeletal Remodeling as a Hallmark and a Vulnerability in Melanoma Therapy Resistance Orgaz JL, Crosas-Molist E, Sadok A et al. Cancer Cell (2020) 37(7) 85-103.e9

Downregulation of Epidermal Growth Factor Receptor in hepatocellular carcinoma facilitates Transforming Growth Factor-β-induced epithelial to amoeboid transition López-Luque J, Bertran E, Crosas-Molist E et al. Cancer Letters (2019) 464(7) 15-24

Regional Activation of Myosin II in Cancer Cells Drives Tumor Progression via a Secretory Cross-Talk with the Immune Microenvironment Georgouli M, Herraiz C, Crosas-Molist E et al. Cell (2019) 176(7) 757-774.e23

Macrophages are exploited from an innate wound healing response to facilitate cancer metastasis Muliaditan T, Caron J, Okesola M et al. Nature Communications (2018) 9(13)

Mets and NETs: The Awakening Force Sanz-Moreno V, Balkwill FR Immunity (2018) 49(1) 798-800

Reactivation of p53 by a Cytoskeletal Sensor to Control the Balance between DNA Damage and Tumor Dissemination Herraiz C, Calvo F, Pandya P et al. Journal of the National Cancer Institute (2016) 108(7)

Epigenetic switch drives the conversion of fibroblasts into proinvasive cancer-associated fibroblasts Albrengues J, Bertero T, Grasset E et al. Nature Communications (2015) 6(13)

TGF-β-Induced Transcription Sustains Amoeboid Melanoma Migration and Dissemination Cantelli G, Orgaz JL, Rodriguez-Hernandez I et al. Current Biology (2015) 25(7) 2899-2914

Diverse matrix metalloproteinase functions regulate cancer amoeboid migration Orgaz JL, Pandya P, Dalmeida R et al. Nature Communications (2014) 5(13)

Team

Postdoctoral researchers in this group
Dr Jose Luis Orgaz Bueno, Dr Irene Rodriguez-Hernandez, Dr Eva Crosas-Molist, Dr Oscar Maiques, Dr Remi Samain

PhD students in this group
Leonie Kohlhammer, Yaiza Jung, Laura Stennett, Anna Perdrix, Samantha George

Biography

I received my first degree in chemistry and later a masters degree in biochemistry from the University of Oviedo in Spain, followed by a PhD in chemical sciences at the University of Cantabria. After a short postdoc in the same lab with a Lady Tata Memorial Trust Fellowship, I moved to the Institute of Cancer Research in London as a CRUK and Marie Curie Intra-european Fellow with Chris Marshall. In 2008, I received an EACR 40th Anniversary Research Award. In 2011 I established my lab with a CRUK Career Development Fellowship at King’s College London (Randall Centre for cell and molecular biophysics). In 2015, I was highly commended as CRUK Communications and Brand Ambassador for communicating science to the public. In 2017 I was awarded the BSCB Women in Cell Biology Early Career Award Medal. The same year I received a CRUK Senior Fellowship and I was badged CRUK Werth Trust Fellow. I joined Barts Cancer Institute as a Professor of Cancer Cell Biology in 2018.