Dr Richard Grose

Dr Richard Grose

BSc, PhD
Centre: Tumour Biology
Reader 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 it 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 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.

Our current research aims:

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. We have shown that nuclear FGFR signalling is a critical mediator of cancer-stroma 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.

3. Modelling breast cancer development in 3D culture

3D modelling fulfils a critical role in research, allowing for complex cell behaviour and interactions to be studied in physiomimetic conditions. We have used the Breast Cancer Now Tissue Bank, an invaluable resource of primary cells isolated directly from patients, to interrogate the interactions between myoepithelial and luminal cells in 3D using collagen gels.

Using lentiviral transduction of isolated cells, we have developed a model that allows us to study early events in breast cancer development, to help understand how breast cancer progresses, with the ultimate aim of improving early diagnosis and treatment.

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 Now
  • Cancer Research UK
  • Pancreatic Cancer Research Fund
  • Rosetrees Trust

Key Publications

Carter EP, Gopsill JA, Gomm JJ, Jones JL, Grose RP. A 3D in-vitro model of the human breast duct: a method to unravel myoepithelial-luminal interactions in the progression of breast cancer. (2017) Breast Cancer Res. In press. DOI 10.1186/s13058-017-0843-4

Dawkins JB, Wang J, Maniati E, Heward JA, Koniali L, Kocher HM, Martin SA, Chelala C, Balkwill FR, Fitzgibbon J, Grose RP. Reduced expression of histone methyltransferases KMT2C and KMT2D correlates with improved outcome in pancreatic ductal adenocarcinoma. (2016) Cancer Research. 76(16):4861-71. PMID: 27280393

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

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


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

  • April 2017 – Congratulations to Ed on getting our “Boob in a Tube” paper aka “A 3D in vitro model of the human breast duct: a method to unravel myoepithelial-luminal interactions in the progression of breast cancer” published in Breast Cancer Research
  • March 2017 – Congratulations Dr Joshua Benjamin Newton Dawkins on being awarded your PhD – fantastic effort, and good luck in the world of Scientific Consultancy!
  • December 2016 – Congratulations to Ed on being awarded a Barts Cancer Institute “Bridge to the Future” fellowship
  • August 2016 – Congratulations Josh on the publication of our pancreatic cancer paper “Reduced Expression of Histone Methyltransferases KMT2C and KMT2D Correlates with Improved Outcome in Pancreatic Ductal Adenocarcinoma” in Cancer Research
  • October 2015 – Congratulations to Ed on getting his first grant - £10,000 from the Rosetrees Trust!
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