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• PhD in Cancer Biology (2003)
• B.Med.Sci (Hons) (1998)

Clare Davies qualified in 1998 with a Bachelor of Medical Science (B.Med.Sc) from the University Â鶹¾«Ñ¡, and continued her studies in Birmingham obtaining a PhD in Cancer Biology at the School of Cancer Sciences. 

Clare was then awarded a CRUK Post-Doctoral Fellowship to work with Dr. Axel Behrens at the CRUK-London Research Institute (LRI) investigating novel mechanisms of gene expression in cancer. It was here that she first encountered arginine methylation and realised that there was still much to be discovered about this protein modification. She then joined Dr. Cathy Tournier’s lab at the University of Manchester where she built on her expertise studying cancer development in vivo using genetically altered mice. 

In October 2012, Clare was awarded a Birmingham Fellowship to join the Institute of Cancer and Genomic Sciences and initiate her own research group investigating the role of arginine methylation in cancer pathogenesis. She has since been awarded an MRC New Investigator Award and a CRUK Programme Foundation Award to continue her research.

• Lecturer for the BSc Biomedical Sciences programme (formally B.Med.Sc).
• Lecturer for MRes Cancer Sciences (Genomics Module).
• Tutorials for BSc Biomedical Sciences, MRes Cancer Sciences and MBChB programmes.

Clare has supervised a number of PhD and postgraduate Masters students to completion. Her first PhD student obtained a Molecular Cell publication and a EMBO Long-term Fellowship to Postdoc at Harvard University. Many of Clare’s Masters students are now enrolled on PhD programmes.

She is always happy to hear from talented and motivated students that are not afraid of hard work, and will benefit from a highly supportive and mentoring environment. 

If you are interested in studying any of these subject areas please contact Clare directly, or for any general doctoral research enquiries, please email mds-gradschool@contacts.bham.ac.uk

Arginine methylation – a new player in cancer pathogenesis

Protein modifications expand the functional diversity of the proteome enabling dynamic modulation of cellular processes, but are often deregulated during cancer pathogenesis. Arginine methylation, catalysed by protein arginine methyltransferases (PRMTs), was identified over 45 years ago, however the significance of this modification for oncogenesis and malignant progression is only just becoming apparent. In particular, expression of many PRMTs correlates with a poorer cancer prognosis and has thus attracted significant attention as a novel drug target. Despite this potential, the mechanisms by which PRMTs contribute to cancer progression is largely unknown. The Davies lab aims to increase our understanding into the biology of PRMTs and arginine methylation.  Using breast cancer as a model, the questions we are currently addressing are:

1) How is PRMT5 regulating the DNA damage response?

We have recently described a role for PRMT5 in homologous recombination-mediated repair of double strand breaks through the methylation of RUVBL1 (Clarke et al., Molecular Cell). We are now taking a variety of molecular, epigenetic, cell biology and proteomic approaches to expand these findings and to fully investigate the importance of arginine methylation in DNA repair and drug resistance.

2) What is the mechanism by which PRMT5 controls the function of breast cancer stem cells?

Breast cancer stem cells (BCSCs) are thought to be the cell of tumour initiation and responsible for disease relapse and metastatic spread. Drug targeting this tumour population is particular challenging as they are relatively resistant to conventional chemotherapies. We have shown that PRMT5 is a key regulator of BCSCs, and that depletion of PRMT5 in a murine tumour model significantly decreased the proportion of BCSCs (Chiang et al. Cell Reports). We found that PRMT5 epigenetically regulates the BCSC transcriptome, leading to gene activation and repression. Future questions will address the other mechanism by which PRMT5 regulates BCSC, and how the epigenome and transcriptome is influenced by arginine methylation.

3) Do PRMTs initiate and/or facilitate cancer progression and can a cancer arginine methylome be identified?

Deletion of PRMT1/5 is embryonic lethal, therefore we use conditional knockout strains of PRMT1 and PRMT5 to study the role of PRMTs for malignant progression within a multicellular organism. We are currently studying mammary gland tumours through intra-ductal delivery of Cre-expressing viruses enabling recombination specially within the ductal tree. In parallel, we are using quantitative proteomics to identify the breast cancer-specific substrate repertoire of PRMT1 and PRMT5.

To address all of these questions, the Davies lab takes a multidisciplinary approach that includes molecular and cell biology, flow cytometry, quantitative proteomics, protein biochemistry (methylation assays, immunoprecipitations), genomic analysis (RNA-Seq and ChIP-Seq), single cell analysis, analysis of patient sample by IHC and functional assays, microscopy and animal models of cancer (genetically engineered, cell line xenografts and patient-derived xenografts (PDXs)). 

Research Groups and Centres: 

Birmingham Centre for Genome Biology (BCGB)

Twitter:

Member of the Biochemical Society.