Dr Julia M.W. Gee - PhD
Member of the School's Pharmacology & Physiology Research Discipline
Current research interests
- Resistance mechanisms during prolonged anti-hormones (Breast Cancer Campaign -funded Scientific Fellowship).
Studies of acquired anti-hormone resistance in breast cancer commonly use relatively short-term (~12month) antihormone-treated in vitro models, implicating erbB receptors, downstream kinases and ER crosstalk. However, targeting such candidate signalling has generally proved disappointing clinically and 2nd-line endocrine agents also have limited benefit. Our group’s recent studies indicate long-term (~3year) acquired antioestrogen-resistant breast cancer cells can recruit novel alternative growth/invasion pathways, gain signalling that decreases/silences ER, and are highly-aggressive, with diminished 2nd-line agent efficacy. The hypothesis for my Fellowship, to be explored using in vitro models and clinical samples, is that the prolonged adjuvant anti-hormone exposure prior to clinical relapse is critical in promoting the resistance mechanism and phenotype. In deciphering mechanism, the aim is to discover new therapeutic targets which could ultimately prove superior to treat clinical breast cancer relapse.
- AstraZeneca-funded projects
(i) Exploration of new targeted therapeutic agents in breast cancer models (e.g. Zactima; pan-erbB inhibitor; mTOR inhibitor,br />(ii) novel gene discovery during response and in resistance to the breast cancer drug Faslodex using microarrays and bioinformatics.
- Study of anti‑hormone impact on tumour suppressors in breast cancer (epigenetics).
- Study of GFR-alpha co-receptor family members in breast cancer (Breast Cancer Campaign and ECMC -funded studies).
- Investigation and exploitation of new biomarkers in clinical breast cancer
This currently includes participation in Cardiff ECMC-funded cancer initiatives and TRICC-funded ABC trial Tamoxifen Late Relapse Study in Breast Cancer.
Further biomarker studies are supported locally by a WORD Translational Health Research Platform Award (e.g. bag-1) and by the “In the Pink” Charity (e.g. CD44 and its variants).
- Gene expression profiling in novel “triple negative” breast cancer model (pilot study funded by CR-UK Cardiff Centre Development Fund)
Current collaborations within the School of Pharmacy and Pharmaceutical Sciences:
- Dr Stephen Hiscox
- Dr Kathryn Taylor
- Professor RI Nicholson.
Current National/International collaborators:
- Prof. J. Robertson, Dr. I Ellis & Dr A. Green (Professorial Unit of Surgery & Dept. Immunopathology, Nottingham City Hospital).
- Dr. P. Barrett-Lee (Velindre Hospital) and Dr. B. Jasani (School of Medicine, Cardiff University).
- Dr. G. Ball (Dept. Bioinformatics, School of Biomedical and Natural Sciences The Nottingham Trent University).
- Dr. I. Hutcheson (Dept Pharmacology, School of Medicine, Cardiff University)
- Dr. R. Clarkson (Dept. Biosciences, Cardiff University)
- Drs. R. Clarke & S. Howell (Breast Biology Group, University of Manchester. Division of Cancer Studies, Paterson Institute for Cancer Research).
- Dr E. Musgrove, Dr. A. Butt (Apoptosis Research Group), Dr. A. Stone and Prof R. Sutherland (Garvan Institute of Medical Research, Darlinghurst, Australia)
- Dr. S Dunn (B.C. Research Institute for Children’s and Women’s Health, Vancouver, Canada).
- C. Huang (Baylor College, Houston, USA).
- Prof. Xiaojiang Cui (John Wayne Cancer Institute, USA)
- Dr. H. Feigl (University of Innsbruck)
- Dr. M. Moe (Medicine, University of Swansea).
- Dr. P. Darbre (School of Biological Sciences, Reading University)
- Prof. A. Thompson (Dept. Surgery, Dundee University);
- Drs. E. Anderson , P. Elvin & S. Guichard (AstraZeneca UK).
- P Bramble, J Chakrabarti (Pfizer UK).
- Breast cancer & clinical and experimental endocrine resistance biology
- Steroid receptor & growth factor receptor signal transduction;
- Novel biomarker & target discovery
- Clinical and experimental immunocytochemistry.
- Gene Microarrays & associated bioinformatics.
Current Research Funding
As Principal applicant:
- Breast Cancer Campaign 5 year Scientific Fellowship award (from Oct. 2010): “Resistance mechanisms during prolonged anti-hormones”, £519,657. This is further supported by a School award of a full-time research technician.
- AstraZeneca “Investigation of mTOR inhibition in breast cancer models responsive and resistant to oestrogen deprivation in vitro.” £130K 2009-2011
- In the Pink Charity “Examination of the adhesion molecule CD44 and its variants in relation to endocrine treatment outcome in clinical breast cancer” £37,000 2010-2011
- Nottingham University “Breast Cancer Study 57: Fulvestrant/aromatase inhibitor treatment of clinical breast cancer steroid receptor and proliferation biomarker research study”. £45,052 2009-2010
- CR-UK Cardiff Centre Development Fund “Profiling of new triple negative breast cancer models” £4833 2010
- WORD Translational Health Research Platform Award “Pilot markers study in breast cancer to assess treatment failure to targeted therapies” £176,369 2009-2011
- AstraZeneca: “Role of HER2/HER3, other signalling pathways and the ability of pan erbB inhibitor to inhibit the growth of EGFR responsive anti-hormone-resistant breast cancer lines” £205,525 2009-2011
- AstraZeneca/BBSRC CASE PhD Studentship: Miss H. Francies (with RI Nicholson & E Anderson) “Deciphering therapeutic resistance in breast cancer”. ~£70K 2009-2013