Dr Richard Grose

Dr Richard Grose

BSc, PhD
Centre: Tumour Biology
Senior Lecturer in Cell Biology
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QMUL Directory


We are interested in how cancer cells signal to each other and to their surrounding cells, and how this knowledge can be exploited to develop novel targeted therapies.

We also investigate how cancer cells develop resistance to these therapies, so that we can design drug combination approaches to overcome the critical clinical problem of drug resistance.

Research Details

Fibroblast growth factor receptor (FGFR) signalling can be a positive driving force for cell proliferation, survival and migration but is kept under tight control via feedback loops. In cancer, these controls can be bypassed by a variety of mechanisms and we are investigating how this happens.

We are focusing currently on breast, pancreatic and endometrial cancer, using 2D and 3D cell based models to investigate how cellular behaviour changes when FGFR signalling is altered. We collaborate with clinical colleagues to determine the clinical significance of our findings through analysis of patient samples.

We have two major arms to our current research:

1. Nuclear trafficking of FGFRs

We have discovered that, rather than signalling from the cell surface or within endosomes, FGFRs can be proteolytically cleaved following activation and that the cytoplasmic portion of the receptor can traffic to the nucleus and regulate gene transcription. We have identified this behaviour in invasive breast cancer cells both in vitro and in vivo.

Our goals are to dissect the mechanisms controlling proteolytic cleavage and trafficking and to identify the full range of target genes and identify novel putative targets to block the pro-invasive effects of nuclear FGFR signalling. Our most recent work has shown that nuclear FGFR signalling is a critical mediator of cancer-stromal cross-talk in pancreatic cancer, and we are exploring the therapeutic potential of FGFR inhibition in blocking pancreatic cancer progression.

2. Targeting oncogene addiction and drug resistance

FGFR2 mutations are key drivers of up to 20% of endometrial cancer and a number of cancers show dependency on oncogenic FGFR signaling, making FGFRs attractive targets for targeted therapies. We have used phosphoproteomics and gene expression analysis to dissect resistance pathways that are established in drug resistant cancer cells, to develop novel combination therapy approaches.

We currently are dissecting these resistance pathways and identifying new targets with implications for many other oncogenic receptor tyrosine kinases.

Profile

  • 1990-91: Research assistant at Amersham. Developing ELISAs for HIV testing
  • 1991-94: BSc in Zoology (University of Bristol)
  • 1994-95: Research Associate at Pfizer Central Research. Molecular Sciences Department
  • 1995-99: PhD (University College London). Molecular basis of embryonic wound repair (Prof Paul Martin)
  • 1999-2001: Postdoctoral researcher (ETH Zurich). Genetically modified mouse models of wound healing (Prof Sabine Werner)
  • 2001-2004: Postdoctoral Fellow (CR-UK LRI). FGF signalling in cancer (Dr Clive Dickson)
  • 2004-present: Group leader at Barts Cancer Institute

Funding

  • Breast Cancer Campaign
  • Cancer Research UK
  • Pancreatic Cancer Research Fund
  • Rosetrees Trust

Key Publications

Coleman SJ, Chioni A-M, Ghallab M, Anderson RK, Lemoine NR, Kocher HM, Grose R. (2014). Pancreatic cancer cell invasion is mediated by nuclear translocation of FGFR1 and FGF2 in stellate cells. EMBO Molecular Medicine. 6:467-481. PMID: 24503018

Robbez-Masson L, Bödör C, Jones JL, Hurst H, Fitzgibbon J, Hart IR, Grose R. (2013). Functional analysis of a breast cancer-associated FGFR2 single nucleotide polymorphism using zinc finger mediated genome editing. PLoS ONE. 8(11):e78839. PMID: 24265722

Chioni A-M and Grose R. (2012). FGFR1 cleavage and nuclear translocation regulates breast cancer cell behavior. Journal of Cell Biology. 197(6):801-17. PMID: 22665522

Turner N, Grose R. (2010). Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer. 10(2): 116-29. PMID: 20094046


Further Publications

For additional publications, please click here.


We are interested in how cancer cells signal to each other and to their surrounding cells, and how this knowledge can be exploited to develop novel targeted therapies.

We also investigate how cancer cells develop resistance to these therapies, so that we can design drug combination approaches to overcome the critical clinical problem of drug resistance.

External Activities

News

October 2015 – Congratulations to Ed on getting his first grant - £10,000 from the Rosetrees Trust!

June 2014 – Congratulations to Abbie on winning the audience vote for best talk at the BCI Postgraduate Day!

March 2014 – Congratulations Myrto on being offered a Lectureship at Kingston University. We are going to miss you deperately but fantastic news all the same…

February 2014 – Congratulations to Abbie on being elected Chair of the 2016 Gordon Research Symposium on FGFs

February 2014 – Congratulations to Stacey on passing her PhD viva with no corrections and publishing her findings in EMBO Molecular Medicine!

November 2013 - Congratulations to Abbie on winning The BACR/Gordon Hamilton-Fairley Young Investigator Award at NCRI for her poster on FGFRs in endometrial cancer.

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