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Molecular Oncology - Richard Marais

Richard obtained his BSc in Genetics and Microbiology from the University College London in 1985, after which he undertook his PhD on Protein Kinase C Isotypes at the Ludwig Institute for Cancer Research in London, which he completed in 1989. He then worked as a Postdoctoral Research Fellow at the Imperial Cancer Research Fund, London, until 1993. Richard then moved to The Institute of Cancer Research (ICR) in London as an Independent Postdoctoral Research Fellow. It was at the ICR where Richard spent the next 19 years of his career focusing on cell signalling in melanoma, developing a particular interest in the role of oncogenic BRAF. During his time at the ICR, Richard progressed to Team Leader of the Signal Transduction Team in 1998, then to Professor of Molecular Oncology in 2007, to Deputy Chair, Section of Cell and Molecular Biology, in 2008, and finally to the Division Head, Division of Cancer Biology, in 2011.

Throughout his career, Richard has received numerous accolades for his contributions to cancer research. In 2007, he was elected Fellow of the Academy of Medical Sciences. In 2009, he was elected Fellow of the European Academy of Cancer Sciences and became an EMBO member. In 2011, he received the Society for Melanoma Research Estella Medrano Memorial Award for outstanding contributions to melanoma research. Richard became Director of the CRUK Manchester Institute in February 2012 where he also continues to head his Molecular Oncology Group. Richard was elected to the Academia Europaea in 2015. In 2016, he received a University of Manchester Researcher of the Year award, as well as The Colin Thomson Memorial Medal from Worldwide Cancer Research and the Fritz Anders medal from the European Society for Pigment Cell Research. In 2017, Richard was awarded the prestigious ARC Foundation Léopold Griffuel Award in Translational and Clinical Research, and the Society for Melanoma Research Outstanding Research Award for major discoveries in melanoma in the last five years. In 2018, he was elected Fellow of the Royal Society.

Introduction

Over the last decade, we have made great strides into understanding the biology of melanoma. The BRAF gene is mutated in about half of melanoma cases, and the NRAS gene is mutated in about 20% of cases. These proteins are part of a conserved signalling pathway that regulates cell proliferation and survival, and the mutant proteins drive uncontrolled cell growth and tumour progression.

Our laboratory focuses on melanoma biology, as well as the biology of other cancers, and we use a combination of approaches, including biochemistry, cell and molecular biology, structural biology, transgenic models and next generation signalling.

We are developing new anti-cancer drugs, and are developing precision medicine protocols to tailor treatments to individual patients. In collaboration with Professor Caroline Springer, now Director of our Drug Discovery Unit, we currently have clinical trials with panRAF drugs that overcome resistance in melanoma to BRAF drugs at The Royal Marsden Hospital and The Christie NHS Foundation Trust. Working with Professor Caroline Dive, our lab has brought whole exome sequencing of patient melanoma samples, and sequencing of naked DNA in plasma, to the clinic to facilitate a new approach to monitoring of disease and response to therapy.

Our aim is to develop multi-disciplinary teams of scientists and clinicians to develop new diagnostic tools and new treatments for cancer patients. 

Selected Publications

Lee RJ, Gremel G, Marshall A, Myers KA, Fisher N, Dunn J, Dhomen N, Corrie PG, Middleton MR, Lorigan P, Marais R. (2017)
Circulating tumor DNA predicts survival in patients with resected high risk stage II/III melanoma.
Annals of Oncology [Epub ahead of print] PubMed abstract

Tang H, Leung L, Saturno G, Viros A, Smith D, Di Leva G, Morrison E, Niculescu-Duvaz D, Lopes F, Johnson L, Dhomen N, Springer C, Marais R. (2017)
Lysyl oxidase drives tumour progression by trapping EGF receptors at the cell surface.
Nature Communications 8:14909. PubMed abstract

Gremel G, Lee RJ, Girotti MR, Mandal AK, Valpione S, Garner G, Ayub M, Wood S, Rothwell DG, Fusi A, Wallace A, Brady G, Dive C, Dhomen N, Lorigan P, Marais R. (2016)
Distinct subclonal tumour responses to therapy revealed by circulating cell-free DNA.
Annals of Oncology 27(10):1959-65. PubMed abstract

Girotti MR, Gremel G, Lee R, Galvani E, Rothwell D, Viros A, Mandal AK, Lim KH, Saturno G, Furney SJ, Baenke F, Pedersen M, Rogan J, Swan J, Smith M, Fusi A, Oudit D, Dhomen N, Brady G, Lorigan P, Dive C, Marais R. (2016)
Application of sequencing, liquid biopsies, and patient-derived xenografts for personalized medicine in melanoma.
Cancer Discovery 6(3):286-99. PubMed abstract

Girotti MR, Lopes F, Preece N, Niculescu-Duvaz D, Zambon A, Davies L, Whittaker S, Saturno G, Viros A, Pedersen M, Suijkerbuijk BM, Menard D, McLeary R, Johnson L, Fish L, Ejiama S, Sanchez-Laorden B, Hohloch J, Carragher N, Macleod K, Ashton G, Marusiak AA, Fusi A, Brognard J, Frame M, Lorigan P, Marais R, Springer C. (2015)
Paradox-Breaking RAF Inhibitors that Also Target SRC Are Effective in Drug-Resistant BRAF Mutant Melanoma.
Cancer Cell 27(1):85-96. Erratum in: Cancer Cell. 2017 31(3):466. PubMed abstract

Viros A, Sanchez-Laorden B, Pedersen M, Furney SJ, Rae J, Hogan K, Ejiama S, Girotti MR, Cook M, Dhomen N and Marais R. (2014)
Ultraviolet radiation accelerates BRAF-driven melanomagenesis by targeting TP53. 
Nature 511(7510):478-82. PubMed abstract

Sanchez-Laorden B, Viros A, Girotti MR, Pedersen M, Saturno, G, Zambon A, Niculescu-Duvaz D, Turajlic S, Hayes A, Gore M, Larkin J, Lorigan P, Cook M, Springer C and Marais R. (2014)
BRAF inhibitors induce metastasis in RAS-mutant and inhibitor-resistant melanoma cells through MEK/ERK pathway reactivation.
Science Signaling 7(318), ra30. PubMed abstract

Girotti MR, Pedersen M, Sanchez-Laorden B, Viros A, Turajlic S, Niculescu-Duvaz D, Zambon A, Sinclair J, Hayes A, Gore M, Lorigan P, Springer C, Larkin J, Jorgensen C, Marais R. (2013)
Inhibiting EGF receptor or SRC family kinase signaling overcomes BRAF inhibitor resistance in melanoma.
Cancer Discovery 3: 158-167. PubMed abstract

Furney SJ, Pedersen M, Gentien D, Dumont AG, Rapinat A, Desjardins L, Turajlic S, Piperno Neumann S, de la Grange P, Roman-Roman S, Stern M.-H., and Marais R. (2013)
SF3B1 mutations are associated with alternative splicing in uveal melanoma.
Cancer Discovery 3(10):1122-9. PubMed abstract

Su F, Viros A, Milagre C, Trunzer K, Bollag C, Spleiss O, Reis-Filho JS, Kong X, Koya RC, Flaherty KT, Chapman PB, Jung Kim M, Hayward F, Martin M, Yang H, Wang Q, Hilton H, Hang JS, Noe J, Lambros M, Geyer F, Dhomen N, Niculescu-Duvaz I, Zambon A, Niculescu-Duvaz D, Preece N, Robert L, Otte NJ, Mok S, Kee D, Ma Y, Zhang C, Habets G, Burton EA, Wong B, Nguyen H, Kockx M, Andries L, Lestini B, Nolop KB, Lee RJ, Joe AK, Troy JL, Gonzalez F, Hutson TE, Puzanov I, Chmielowski B, Springer CJ, McArthur GA, Sosman JA, Lo RS, Ribas A, Marais R. (2012)
RAS mutations in cutaneous squamous cell carcinomas with BRAF inhibitors.
The New England Journal of Medicine 366: 207-215. PubMed abstract

Team

Associate Scientists
Nathalie Dhomen
Valeria Pavet

Senior Clinical Scientist
Martin Cook

Senior Research Scientist
Adele Green

Postdoctoral Fellows
Alessio Cannistraci
Candelaria Bracalente
Elena Galvani
Franziska Baenke
HaoRan Tang
Katharina Mahal
Lucas Trucco
Pauline Hascoët
Piyushkumar Mundra
Shambhavi Srivastava

Clinical Fellows
Pablo Garcia Martinez
Rebecca Lee
Sara Valpione

Scientific Officers
Christopher Chester
Clare McManus
Darryl Coles
Joshua Tweedy
Megan Grant
Paul Montgomery
Philippa Middlehurst
Rebecca Atkinson-Dell

Translational Research Project Manager
Jackie Mitchell

Graduate Students
Denys Holovanchuk
Luke Chisholm
Matthew Wilson