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

• AECC Excellence Program Evaluation Committee (2022-)
• Cancer Research UK Research Careers Committee (2021-)
• Scientific Advisory Board in TN-ETN "Biomechanics in health and disease" (2020-)
• AACR-CRUK Transatlantic Postdoctoral Fellowships Scientific Review Committee (2019-)
• Life Sciences Committee for Postdoctoral Fellowships from La Caixa Fellowship Programme (2018-2021)
• PhD programme, INPhINIT, (co-funded by Horizon 2020 Marie Skłodowska-Curie actions and “la Caixa” Foundation) Evaluating Committee (2017-2019)

Major Funding

• 2022-2024- Worldwide Cancer Research, 'Targeting mechano-sensing leading to metabolic reprogramming to prevent melanoma metastasis'
• 2018-2024- Barts Charity, 'Targeting the Tumour Microenvironment'
• 2017-2024- Cancer Research UK Senior Fellowship & CRUK Werth Trust Fellow, 'Investigating Rho-kinase (ROCK) in melanoma progression and therapy response'
• 2022-2024- Margarita Salas Postdoctoral Fellowship for Dr Lourdes Chulia (Universidad Valencia), 'Role of cancer-associated fibroblasts (CAFs) in the acquisition of aggressive and invasive melanoma amoeboid features'

Recent Publications

The amoeboid state as part of the epithelial-to-mesenchymal transition programme Graziani V, Rodriguez-Hernandez I, Maiques O et al. Trends in Cell Biology (2022) 32(7) 228-242

Location, location, location: Melanoma cells “living at the edge” Maiques O, Sanz-Moreno V Experimental Dermatology (2022) 31(7) 82-88

RHO GTPase SIGNALING IN CANCER PROGRESSION AND DISSEMINATION Crosas-Molist E, Samain R, Kohlhammer L et al. Physiological Reviews (2022) 102(7) 455-510

Podoplanin drives dedifferentiation and amoeboid invasion of melanoma de Winde CM, George SL, Crosas-Molist E et al. iScience (2021) 24(7)

A preclinical pipeline to evaluate migrastatics as therapeutic agents in metastatic melanoma Maiques O, Fanshawe B, Crosas-Molist E et al. British Journal of Cancer (2021) 125(7) 699-713

Kallikrein-related peptidase 6 is associated with the tumour microenvironment of pancreatic ductal adenocarcinoma Candido JB, Maiques O, Boxberg M et al. Cancers (2021) 13(7)

LAP1 supports nuclear plasticity during constrained migration Jung-Garcia Y, Maiques O, Rodriguez-Hernandez I et al. (2021) (18)

Early functional mismatch between breast cancer cells and their tumour microenvironment suppresses long term growth Rosell AP, Maiques O, Chakravarty P et al. (2021) (18)

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

Team

Postdoctoral researchers

• Dr Eva Crosas-Molist
• Dr Oscar Maiques
• Dr Remi Samain
• Dr Vittoria Graziani
• Dr Lourdes Chulia

PhD students

• 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.