Understanding the factors and pathways involved in breast cancer progression and resistance to therapy
Division of Cancer Research
Jacqui Wood Cancer Centre
University of Dundee
James Arrott Drive
Ninewells Hospital And Medical School
+(44) 01382 383282
Frances Fuller-Pace carried out her PhD studies with Professor Noreen Murray, firstly at EMBL Heidelberg, and subsequently at the University of Edinburgh. After post-doctoral fellowships in Dr Peter Southern’s lab at the Scripps Research Institute in San Diego, California, and in Dr Clive Dickson’s lab at the Imperial Cancer Research Fund (now CRUK) in London, she joined Prof. Sir David Lane’s lab at Dundee to work on the DEAD box family of RNA helicases. She was awarded an MRC Senior Fellowship on 1992, which allowed her to set up an independent research group and which she renewed in 1997. Frances was elected a Fellow of the Higher Education Academy in 2007 and a Fellow of the Royal Society of Biologists in 2010. Work in the Fuller-Pace lab focuses on the role of RNA helicases in breast cancer development and progression and on factors that influence the response to chemotherapy and endocrine therapy, and is supported by Breast Cancer Now and Tenovus Scotland.
My group's main research interests are in the factors underlying breast cancer progression and chemotherapy/endocrine therapy resistance, with a focus on the role of the multi-functional RNA helicases p68 (DDX5) and p72 (DDX17) and their interactions with the tumour suppressor p53 and with nuclear hormone receptors in this process.
Together with our clinical colleagues we are also interested in exploring the importance of the peri-tumoral stroma in the response to neoadjuvant therapy in breast cancer. This is a collaboration that combines gene expression and functional analysis of tumoral and peri-tumoral fibroblasts (our own work) combined with Magnetic Resonance Imaging (MRI) and Shear Wave Elastography of breast cancers (clinical radiologists) and Pathology with the long-term view of predicting response to neoadjuvant chemotherapy.
Our main research aims:
· Understanding how the function of p68 and p72 as transcriptional co-regulators modulates the p53 response to DNA damage.
· Analysis of cross talk between p68/p72 and nuclear hormone receptors, and their impact on the development of therapy resistance.
· Understanding the role of differences in gene expression patterns in breast tumoral and peri-tumoral fibroblasts, both in the response to neoadjuvant chemotherapy and in tumour cell migration/invasion.
To address these questions we are using a combination of molecular and cell culture techniques together with analysis of patient tumour material.
1. Patel H, Abduljabbar R, Lai C-F, Periyasamy M, Harrod A, Gemma C, Steel JH, Patel N, Busonero C, Jerjees D, Remenyi J, Smith S, Gomm JJ, Magnani L, Győrffy B, Jones LJ, Fuller-Pace F, Shousha S, Buluwela L, Rakha EA, Ellis IO, Coombes RC, Ali S (2016) Expression of CDK7, cyclin H and MAT1 is elevated in breast cancer and is prognostic in estrogen receptor positive breast cancer. Clinical Cancer Research Epub.
3. Kramer HB, Lai C-F, Patel H, Periyasamy M, Lin M-L, Feller SM, Fuller-Pace FV, Meek DW, Ali1 S, & Buluwela L (2016) LRH-1 drives colon cancer cell growth by repressing the expression of the CDKN1A gene in a p53-dependent manner. Nuc Acids Res 29: 582-594.
4. Huang W, Thomas B, Flynn RA, Gavzy SJ, Wu L, Kim SV, Hall JA, Miraldi ER, Ng CP1, Rigo FW, Meadows S, Montoya NR, Herrera NG, Domingos AI, Rastinejad F, Myers RM, Fuller-Pace FV, Bonneau R, Chang HY, Acuto O, Littman DR (2015) DDX5 and its associated lncRNA Rmrp modulate TH17 cell effector functions. Nature 528: 517-522.
5. Periyasamy M, Patel H, Lai C-F , Nguyen VTM, Nevedomskaya E, Harrod A, Russell R, Remenyi R, Ochocka AM, Thomas RS, Fuller-Pace F, Gyorffy B, Caldas C, Navaratnam N, Carroll JS, Zwart W, Coombes RC, Magnani L, Buluwela L, and Ali S (2015) APOBEC3B-Mediated Cytidine Deamination Is Required for Estrogen Receptor Action in Breast Cancer. Cell Reports 13: 108-121.
6. Lin ML, Patel H, Remenyi J, Banerji CR, Lai CF, Periyasamy M, Lombardo Y, Busonero C, Ottaviani S, Passey A, Quinlan PR, Purdie CA, Jordan LB, Thompson AM, Finn RS, Rueda OM, Caldas C, Gil J, Coombes RC, Fuller-Pace FV, Teschendorff AE, Buluwela L, Ali S (2015) Expression profiling of nuclear receptors in breast cancer identifies TLX as a mediator of growth and invasion in triple-negative breast cancer. Oncotarget 6: 21685-21703.
7. Iyer RS, Nicol SM, Quinlan PR, Thompson AM, Meek DW & Fuller-Pace FV (2014) The RNA helicase/transcriptional co-regulator, p68 (DDX5), stimulates expression of oncogenic protein kinase, Polo-like kinase-1 (PLK1), and is associated with elevated PLK1 levels in human breast cancers. Cell Cycle 13:9, 1-11.
8. Clark EL, Hadjimichael C, Temperley R, Barnard A, Fuller-Pace FV, Robson CN (2013) p68/DdX5 Supports β-Catenin & RNAP II during Androgen Receptor Mediated Transcription in Prostate Cancer. PLoS One 8: e54150. doi: 10.1371.
9. Nicol SM, Bray SE, Black HD, Lorimore SA, Wright EG, Lane DP, Meek DW, Coates PJ & Fuller-Pace FV (2013) The RNA helicase p68 (DDX5) is selectively required for the induction of p53-dependent p21 expression and cell cycle arrest after DNA damage. Oncogene 32: 3461-3469.
10. Moore HC, Johnston M, Nicol SM, Bourdon J-C, Thompson AM, Hutvagner G & Fuller-Pace FV. (2011) An evolutionarily conserved intron in the p68/DDX5 DEAD box RNA helicase gene encodes a novel miRNA. RNA 17: 555-562.
11. Moore HC, Jordan LB, Bray SE, Baker L, Quinlan PR, Purdie CA, Thompson AM, Bourdon J-C & Fuller-Pace FV. (2010) The RNA helicase p68 modulates expression and function of the D133 isoform(s) of p53, and is inversely associated with D133p53 expression in breast cancer. Oncogene 29: 6475-6484.
12. McKenzie L, King S, Marcar L, Nicol S, Dias S, Schumm K, Robertson P, Bourdon J-C, Perkins N, Fuller-Pace F & Meek DW. (2010) p53-dependent repression of polo-like kinase-1 (PLK1). Cell Cycle 9: 1-13.
13. Wortham NC, Ahamed E, Nicol SM, Thomas RS, Periyasamy M, Jiang J, Ochocka AM, Shousha S, Bray SE, Ali S. & Fuller-Pace FV. (2009) The DEAD box protein p72 regulates ER-/Oestrogen-dependent transcription and cell growth, and is associated with improved survival in ER positive breast cancer. Oncogene 28: 4053-4064.
14. Hofmann WA, Arduini A, Nicol SM, Camacho CJ, Lessard JL, Fuller-Pace FV & de Lanerolle, P. (2009) SUMOylation of nuclear actin. J. Cell Biol. 186: 193-200.
15. Logan IR, McNeill HV, Cook S, Ly X, Meek DW, Fuller-Pace FV, Lunec J & Robson CN. (2009) Heat shock factor-1 modulates p53 activity in the transcriptional response to DNA damage. Nuc. Acids Res. 37: 2962-2973.
16. Ochocka AM, Kampanis P, Nicol S, Allende-Vega N, Cox M, Marcar L, Milne D, Fuller-Pace F & Meek D. (2009) FKBP25, a novel regulator of the p53 pathway, induces the degradation of MDM2 and activation of p53. FEBS Lett. 583: 621-628.
17. Clark EL, Coulson A, Dalgliesh C, Rajan P, Nicol SM, Fleming S, Heer R, Gaughan L, Leung HY, Elliot DJ, Fuller-Pace FV & Robson CN. (2008) The RNA helicase p68 is a novel androgen receptor coactivator involved in splicing and is overexpressed in prostate cancer. Cancer Res. 68: 7938-7946.
18. Jensen ED, Niu L, Caretti G, Nicol SM, Teplyuk N, Stein GS, Sartorelli V, van Wijnen A, Fuller-Pace FV and Westerndorf JJ. (2008) Ddx5 (p68) interacts with Runx2 and regulates Osteoblast differentiation. J. Cell. Biochem. 103, 1438-1451.
19. Jacobs A-MF, Nicol SM, Hislop RG, Jaffray EG, Hay RT and Fuller-Pace FV. (2007) SUMO modification of the DEAD box protein p68 modulates its transcriptional activity and promotes its interaction with HDAC1. Oncogene 26: 5866-5876.
20. Caretti G, Schiltz RL, Dilworth FJ, Di Padova M, Zhao P, Ogryzko V, Fuller-Pace FV, Hoffman EP, Tapscott SJ, & Sartorelli V. (2006) The RNA helicases p68/p72 and the noncoding RNA SRA are coregulators of MyoD and skeletal muscle differentiation. Dev. Cell 11: 547-560.
21. Bates GJ, Nicol SM, Wilson BJ, Jacobs, A-MF, Bourdon J-C, Wardrop J, Gregory DJ, Lane DP, Perkins ND & Fuller-Pace FV. (2005) The DEAD box protein p68: a novel transcriptional coactivator of the p53 tumour suppressor. EMBO J. 24: 543-553.
1. Fuller-Pace FV (2013) The DEAD box proteins DDX5 (p68) and DDX17 (p72): Multi-tasking transcriptional regulators. Biochim Biophys Acta 1829: 756-763.
2. Linder P, Fuller-Pace FV (2013) The biology of RNA helicases- modulation for life. Biochim Biophys Acta 1829: 749 (Preface).
3. Linder P, Fuller-Pace FV (2013) Looking back on the birth of DEAD-box RNA helicases Biochim Biophys Acta 1829: 750-755.
4. Fuller-Pace FV (2013) DEAD box RNA helicase functions in cancer. RNA Biology 10: 121-132.
5. Fuller-Pace FV & Moore HC (2011) RNA helicases p68 and p72: multifunctional proteins with important implications for cancer development. Future Oncology 7: 239-251.
6. Clark EL, Fuller-Pace FV, Elliott DJ & Robson CN. (2008) Coupling Transcription to RNA Processing via the p68 DEAD box RNA Helicase Androgen Receptor Co-Activator in Prostate Cancer. Biochem. Soc. Trans. 36: 546-547.
7. Fuller-Pace FV & Ali, S. (2008) The DEAD box RNA helicases p68 (Ddx5) and p72 (Ddx17): novel transcriptional co-regulators. Biochem. Soc. Trans. 36: 609-612.
8. Fuller-Pace FV, Jacobs A-MF & Nicol SM. (2007) Modulation of transcriptional activity of the DEAD box RNA helicases p68 (Ddx5) and DP103 (Ddx20) by SUMO modification. Biochem. Soc. Trans. 35: 1427-1429.
9. Fuller-Pace, FV (2006) DExD/H box RNA helicases: multifunctional proteins with important roles in transcriptional regulation. Nuc. Acids Res. 34: 4206-4215.
1. Linder P & Fuller-Pace F (2014) Happy Birthday: 25 years of DEAD-box proteins. In Methods in Molecular Biology, Accepted- In Press.
2. Fuller-Pace FV & Nicol SM (2012) DEAD box RNA helicases as transcription factors. In Methods in Enzymology, Elsevier Academic Press, 511: 347-367.
3. Nicol SM & Fuller-Pace FV. (2010) Analysis of the RNA helicase p68 (Ddx5) as a transcriptional regulator. In Methods in Molecular Biology, Humana Press, 587: 265-279.
Frances Fuller-Pace has been actively involved in undergraduate and postgraduate teaching for many years, both through lecturing and through supervising undergraduate and postgraduate (MRes and PhD) students. She has previously been involved in coordinating BMSc and student selected courses for undergraduate MBChB students and was one of the original team who set up the MRes Cancer Biology course in 2010. She was a module lead until May 2015, when she took over as Programme Coordinator.
Frances coordinates the monitoring of all PhD students in the Cancer Division and is a member of the Research Degrees Committee, which oversees the research postgraduate programme in the Medical School. She is also a member of the Medical School Taught Postgraduate Committee, the Postgraduate Research Programme Development Committee and the Equality and Diversity Committee. She is also a Disability Support Officer for the Medical School.
1. Course coordinator for the MRes Cancer Biology course.
2. Medical School Lead for MSci in Biomedical Sciences.
3. Lecturer in Cancer Biology: Level 3 and Level 4(Hons-, BSc Biomedical sciences; BMSc Genetics, Cancer and Personalised Medicine.
4. Division Lead for monitoring of PhD students.
Frances has supervised several PhD students and is currently co-supervisor for 2 students.
Frances Fuller-Pace has given invited seminars in the UK, Europe, USA, China, India and Singapore. She regularly participates in international conferences and co-organised the EMBO-Harden international conference on helicases in Cambridge in 2013.