Professor Richard Grose

BSc, PhD
Professor of Cancer Cell Biology
Group Leader
Twitter
Research Focus

We are interested in how cancer cells interact with each other and the microenvironment. We investigate how cancer cells develop resistance to therapies and design drug combination approaches to overcome this.

Key Publications

PHLDA1 mediates drug resistance in receptor tyrosine kinase driven cancer. Cell Reports (2018) 22:1-13. PMID: 29490281

Pancreatic cancer cell invasion is mediated by nuclear translocation of FGFR1 and FGF2 in stellate cells. EMBO Mol Med (2014) 6:467-481. PMID: 24503018

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

The role of fibroblast growth factor receptor 2b in skin homeostasis and cancer development. EMBO Journal (2007) 26(5):1268-78. PMID: 17304214

Major Funding
  • 2019-2023- Cancer Research UK, Myoepithelial degradome in the progression of DCIS to invasive breast cancer, £473,002
  • 2018-2020- Breast Cancer Now, Myoepithelial/luminal cross-talk in the progression of DCIS to invasive breast cancer, £201,816.00
Other Activities
Research

Receptor Tyrosine Kinase (RTK) 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 focus on breast, pancreatic and endometrial cancer, using 2-D and 3-D cell-based models to investigate how cellular behaviour changes when RTK signalling is altered. We collaborate with clinical colleagues to determine the translational significance of our findings through analysis of patient samples.

Our current research aims:

1. Targeting oncogene addiction and drug resistance

Fibroblast Growth Factor Receptor (FGFR) 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 have recently identified a new resistance pathway, mediated by PHLDA1 dependent regulation of Akt signalling, with implications for targeted therapies against both FGFRs and HER2. In an exciting new project, we are now adopting similar approaches to identify drug resistance mechanisms in glioblastoma.

2. 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.

3. 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.

Other Activities
Major Funding
  • 2019-2023- Cancer Research UK, Myoepithelial degradome in the progression of DCIS to invasive breast cancer, £473,002
  • 2018-2020- Breast Cancer Now, Myoepithelial/luminal cross-talk in the progression of DCIS to invasive breast cancer, £201,816.00
  • 2009-2010- Medical Research Council, Tumour suppressive function of Fgfr2b, £343,676.00
Recent Publications

Pancreatic Cancer Organotypic Models. Coetzee A, Grose R, Kocher H Curr Top Microbiol Immunol (2019) (2)
https://www.ncbi.nlm.nih.gov/pubmed/30790075

Emerging Roles of Fibroblast Growth Factor 10 in Cancer. Clayton NS, Grose RP Front Genet (2018) 9(1) 499-499
https://www.ncbi.nlm.nih.gov/pubmed/30405704

PHLDA1 Mediates Drug Resistance in Receptor Tyrosine Kinase-Driven Cancer Fearon AE, Carter EP, Clayton NS et al. Cell Reports (2018) 22(7) 2469-2481

Fibroblast growth factor-mediated crosstalk in cancer etiology and treatment. Clayton NS, Wilson AS, Laurent EP et al. Dev Dyn (2017) 246(1) 493-501
https://www.ncbi.nlm.nih.gov/pubmed/28470714

A 3D in vitro model of the human breast duct: A method to unravel myoepithelial-luminal interactions in the progression of breast cancer Carter EP, Gopsill JA, Gomm JJ et al. Breast Cancer Research (2017) 19(7)

3D Organotypic Culture Model to Study Components of ERK Signaling. Chioni A-M, Bajwa RT, Grose R Methods Mol Biol (2017) 1487(1) 255-267
https://www.ncbi.nlm.nih.gov/pubmed/27924573

A 3D in vitro model of the human breast duct: unravelling myoepithelial-luminal interactions in breast cancer Carter E, Gomm JJ, Jones LJ et al. Breast Cancer Research and Treatment (2016) 159(1) 187-188

Anti-stromal treatment together with chemotherapy targets multiple signalling pathways in pancreatic adenocarcinoma. Carapuça EF, Gemenetzidis E, Feig C et al. Journal of Pathology (2016) 239(1) 286-296

Reduced expression of histone methyltransferases KMT2C and KMT2D correlates with improved outcome in pancreatic ductal adenocarcinoma GROSE RP, Dawkins JBN, Wang J et al. Cancer Research (2016) (1)
http://www.bci.qmul.ac.uk/staff/item/richard-grose

Dysregulated FGF signalling in neoplastic disorders Tanner Y, Grose RP Seminars in Cell and Developmental Biology (2016) 53(1) 126-135

For additional publications, please click here
Team

Postdoctoral Researchers
Dr Edward Carter, Dr Lucía Rodríguez Fernández, Dr Chris Milton

PhD Students
Ms Yasmine Tanner, Ms Abigail Wilson, Demi Wiskerke

Biography
  • 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