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

WNT11-FZD7-DAAM1 signalling supports tumour initiating abilities and melanoma amoeboid invasion Rodriguez-Hernandez I, Maiques O, Kohlhammer L et al. Nature Communications (2020) 11(7)

First-in-Human Study of AT13148, a Dual ROCK-AKT Inhibitor in Patients with Solid Tumors McLeod R, Kumar R, Papadatos-Pastos D et al. Clinical Cancer Research (2020) 26(7) 4777-4784

CDC42EP5/BORG3 modulates SEPT9 to promote actomyosin function, migration, and invasion Farrugia AJ, Rodríguez J, Orgaz JL et al. Journal of Cell Biology (2020) 219(7)

Cancer Burden Is Controlled by Mural Cell-β3-Integrin Regulated Crosstalk with Tumor Cells Wong PP, Muñoz-Félix JM, Hijazi M et al. Cell (2020) 181(7) 1346-1363.e21

What does not kill you makes you stronger: surviving anti-cancer therapies by cytoskeletal remodeling and Myosin II reactivation Orgaz JL, Sanz-Moreno V Molecular and Cellular Oncology (2020) 7(7)

Erratum: PAK4 Kinase Activity Plays a Crucial Role in the Podosome Ring of Myeloid Cells (Cell Reports (2019) 29(11) (3385–3393.e6), (S2211124719314871), (10.1016/j.celrep.2019.11.016)) Foxall E, Staszowska A, Hirvonen LM et al. Cell Reports (2020) 31(7)

Cancer-associated fibroblasts: activin A adds another string to their bow Samain R, Sanz-Moreno V EMBO Molecular Medicine (2020) 12(7)

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

PGC1a suppresses prostate cancer cell invasion through ERRA transcriptional control Valcarcel-Jimenez L, Macchia A, Crosas-Molist E et al. Cancer Research (2019) 79(7) 6153-6165

PAK4 Kinase Activity Plays a Crucial Role in the Podosome Ring of Myeloid Cells Foxall E, Staszowska A, Hirvonen LM et al. Cell Reports (2019) 29(7) 3385-3393.e6

Team

Postdoctoral researchers in this group
Dr Eva Crosas-Molist, Dr Oscar Maiques, Dr Remi Samain, Dr Vittoria Graziani

PhD students in this group
Leonie Kohlhammer, Samantha George, Jaume Barcelo, Yaiza Jung, Josh Martin

Research Assistant
Jo Monger

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.