Dr Julia M.W. Gee

Breast Cancer Campaign Senior Research Fellow

Ysgol Fferylliaeth a Gwyddorau Fferyllol

: gee@cardiff.ac.uk
: +44 (0)29 2087 4922

: Ar gael fel goruchwyliwr ôl-raddedig

Qualifications

BSc. (Hons) Physiological Sciences, University of Newcastle, 1985
PhD in Cancer Biology, University of Wales, 1991

Funding bodies which support our work

Breast Cancer Campaign
CRUK Cardiff Centre Development Fund & ECMC Cardiff
The Wales Cancer Institute
"In The Pink" Charity
Welsh Assembly Government (Wales Office of Research & Development for Health & Social Care [WORD])

I received a BSc (Hons) in 1985 in Physiological Sciences from the University of Newcastle-Upon-Tyne and was awarded the University's Physiology prize for that year. I then undertook a Medical Research Council-funded PhD studentship at the University of Wales College of Medicine in the then Tenovus Institute (breast cancer laboratory, PhD awarded 1991).

I held 3 consecutive postdoctoral positions in the Tenovus Institute between 1991-2000 (including one with Dept. Surgery, University of Wales College of Medicine), becoming a Senior Researcher in 1995.

Between 2000-April 2007, I took up the position of Senior Research Associate & Research Co-ordinator for the Tenovus Centre for Cancer Research within the School of Pharmacy and Pharmaceutical Sciences, where the programme of work focussed around anti‑hormone resistance and progression in breast cancer. Alongside contributing to the management of (and defining research strategies for) the Tenovus group, my role was to oversee the Clinical Immunocytochemistry Team, extending to analysing signalling elements using activation-specific antibodies in several phase II breast cancer trials.

I also lead the group's Gene Discovery Team applying microarrays and bioinformatics to reveal new signalling in resistant breast cancer, and receiving a gold medal in this area at the 9th World Congress on Advances in Oncology/7th International Symposium on Molecular Medicine. I was subsequently funded until Sept. 2010 as Principal Investigator on a Tenovus Charity programme grant investigating and targeting anti‑hormone-induced signalling during the drug responsive phase of ER+ breast cancer.

Most recently, I successfully secured a prestigious 5-year Breast Cancer Campaign-funded Senior Scientific Fellowship (2010-2015), based in the School of Pharmacy and Pharmaceutical Sciences, to examine the impact of prolonged antihormone exposure on the acquired resistant phenotype in ER+ disease to define targets potentially relevant following adjuvant antihormone relapse in the clinic.

Alongside defining research strategies for further funding bids, my current role extends to formulating new hypotheses and contributing to management and implementing projects, development and strategic planning for our research group. I am also responsible for securing supportive external grant funding and for sustaining various existing (and securing new) collaborations with key academic groups and pharmaceutical companies.

I am principal investigator/co-applicant on several industrial-funded studies exploring new therapeutic agents within breast cancer models.

Relationship with practitioners

Alongside contributing to mentoring of several Cardiff and Nottingham-based MD studentships, I have managed research assays for immunocytochemical markers in the Tenovus Centre for Cancer Research, notably monitoring steroid receptors and growth factor receptor signalling pathway elements in several clinical trials in breast cancer (collaborating substantially with Prof. John Robertson at Dept. Surgery, Nottingham City Hospital).

These have included studies with (i) the anti‑hormone Faslodex (Fulvestrant) in breast cancer (e.g. Study 41; NEWEST trial) and (ii) Gefitinib in Tamoxifen resistant breast cancer and also DCIS.

My team was a key player in the Phase II clinical biomarker studies that provided primary evidence for FDA/EU approval of Faslodex in advanced breast cancer.

Currently we are contributing to biomarker analysis in the multicentre ABC tamoxifen relapse breast cancer study and have strong local collaborations with breast cancer oncologist Prof. Peter Barrett-Lee at Velindre Hospital.

Aelodaethau proffesiynol

British Breast Group elected member.
Invited member of Editorial Board for Journal of Hormone Molecular Biology and Clinical Investigation 2010
Invited member of Editorial Board for BMC Cancer Journal 2010
Invited member of Editorial Board for Endocrinology Journal 2009-2012
Co-editor for 1st-3rd Tenovus/AstraZeneca Workshops (2005, 2006, 2008).
I served as an invited Reporter for Breast Cancer Research Online 2003-2006.
Regular referee & peer reviewer for scientific journals including JNCI, Nature journals, Breast Cancer Research, Endocrinology, & for funding bodies including
CR-UK (TRICC), MRC, Yorkshire Cancer Research; Irish Cancer Fund; Breast Cancer Campaign; Weston Park Hospital Sheffield

Ymrwymiadau siarad cyhoeddus

"Anti-Hormone induced compensatory signalling in breast cancer: an adverse event in the development of endocrine resistance", 1st International Symposium of Journal of Hormone Molecular Biology and Clinical investigation, Seefeld, Austria, Sept 2010.

Public engagement

Interaction with Breast Cancer Campaign and "In The Pink" charities & fundraisers.
Presenting Breast Cancer Researcher (Biomarkers) at CR-UK Centre Cardiff public launch October 2009
Contributor to Breast Cancer Campaign "History of Breast Cancer" public document 2010

Pwyllgorau ac adolygu

Postdoctoral representative on School of Pharmacy and Pharmaceutical Sciences Research Committee from 2010
Founder Member of School of Pharmacy and Pharmaceutical Sciences Postdoctoral Researchers College
Active member of Wales Cancer Institute Breast Group, Cardiff CRUK-ECMC group, & Sartre Cardiff/Bristol Cancer group
Current member (& named co-applicant) of ABC breast cancer trial (TRICC tamoxifen relapse) study group
British Breast Group elected member, and recently-elected Scientific Programme Committee member from 2010
Invited Member of Tissue Bank Access Committee for Breast Cancer Campaign Charity from 2010
British Breast Cancer Research Conference Scientific Board member, Nottingham UK, from January 2010
Breast Cancer Campaign Scientific Meeting Organising Committee member since 2006. Also Committee Member for (and co-author of resulting document for) National Gap Analysis in breast cancer instigated by Breast Cancer Campaign. This highlighted priority areas for breast cancer scientific research in the UK. Thompson A, Brennan K, Cox A, Gee J, Harcourt D, Harris A, Harvie M, Holen I, Howell A, Nicholson R, Steel M, Streuli C. Evaluation of the current knowledge limitations in breast cancer research: a gap analysis. Breast Cancer Res. 2008;10(2):R26.
Organising Committee member Tenovus/AstraZeneca Workshops on Cancer (1st, 2005; 2nd, 2006; 3rd, Workshop "Therapeutic Resistance to anti-hormonal drugs in breast cancer: new molecular aspects and targets" May 2008, Cardiff). Proceedings from these Workshops were published as supplements in the journal Endocrine Related Cancer and in the Springer book publication (2009) "Therapeutic resistance to anti-hormonal drugs in breast cancer: new molecular aspects and their potential as targets".
Previous Scientific Advisory Board member for Breast Cancer Campaign (2004-2007)
Previous member of Oncopool ("Pooling of European Data to Harmonise Translational Research in Breast Cancer") European Breast Cancer Study Group (2002-2004)
NEQAS Immunocytochemistry Co-ordinator for Tenovus Centre for Cancer Research (2001-2008)
Previously served on AstraZeneca Pathology Review & Molecular Targets in Breast Cancer Advisory Panels (2001; April 2008)

1994

Gee, J. M. W.et al. 1994. Immunocytochemical localization of BCL-2 protein in human breast cancers and its relationship to a series of prognostic markers and response to endocrine therapy. International Journal of Cancer 59(5), pp. 619-628. (10.1002/ijc.2910590508)
Nicholson, R. I.et al. 1994. Transforming growth factor-α and endocrine sensitivity in breast cancer. Cancer Research 54(7), pp. 1684-1689.
Nicholson, R. I.et al. 1994. Epidermal growth factor receptor expression in breast cancer: Association with response to endocrine therapy. Breast Cancer Research and Treatment 29(1), pp. 117-125. (10.1007/BF00666187)
Manning, D. L.et al. 1994. Oestrogen-regulated genes in breast cancer: Association of pLIV1 with lymph node involvement. European Journal of Cancer 30(5), pp. 675-678. (10.1016/0959-8049(94)90543-6)
Nicholson, R. I.et al. 1994. Pure anti-oestrogens (ICI 164384 and ICI 182780) and breast cancer: is the attainment of complete oestrogen withdrawal worthwhile?. Endocrine-Related Cancer 1(4), pp. 5-17. (10.1677/erc.0.0010005)
Ghandour, F. A.et al. 1994. Immunocytochemical localization of oestrogen and progesterone receptors in primary adenocarcinoma of the cervix. Histopathology 24(1), pp. 49-55. (10.1111/j.1365-2559.1994.tb01270.x)
Nicholson, R. I.et al. 1994. Pure antioestrogens in breast cancer - experimental and clinical observations. Presented at: Sex Hormones and Antihormones in Endocrine Dependent Pathology: Basic and Clinical Aspects: International Symposium, Milano, Italy, 10-14 April 1994 Presented at Motta, M. and Serio, M. eds.Sex Hormones and Antihormones in Endocrine Dependent Pathology: Basic and Clinical Aspects: Proceedings of an International Symposium, Milano, Italy, 10-14 April 1994. International Congress Series Vol. 1064. Amsterdam: Elsevier Science pp. 347-360.

1993

Schmid, K. W.et al. 1993. Presence and possible significance of immunocytochemically demonstrable metallothionein over-expression in primary invasive ductal carcinoma of the breast. Virchovs Archiv 422(2), pp. 153-159. (10.1007/BF01607167)
Manning, D. L.et al. 1993. The role of four oestrogen-responsive genes, pLIV1, pS2, pSYD3 and pSYD8, in predicting responsiveness to endocrine therapy in primary breast cancer. European Journal of Cancer 29(10), pp. 1462-1468. (10.1016/0959-8049(93)90021-7)

1992

Jasani, B.et al. 1992. Dinitrophenyl (DNP) hapten sandwich staining (DHSS) procedure: A 10 year review of its principle reagents and applications. Journal of Immunological Methods 150(1-2), pp. 193-198. (10.1016/0022-1759(92)90078-8)

1991

Gee, J. M. W.et al. 1991. Use of the dinitrophenyl hapten sandwich staining procedure (DHSS) to localize estrogen receptors in paraffin-embedded tissues. Journal of Histochemistry & Cytochemistry 39(12), pp. 1659-1670. (10.1177/39.12.1719072)

1990

Nicholson, R. I.et al. 1990. Estrogen Deprivation in Breast Cancer: Clinical, Experimental, and Biological Aspects. In: Castagnetta, L. et al. eds. Steroid Formation, Degradation, and Action in Peripheral Tissues. Annals of the New York Academy of Sciences Vol. 595. New York: New York Academy of Sciences, pp. 316-327., (10.1111/j.1749-6632.1990.tb34305.x)
Gee, J. M. W.et al. 1990. An immunocytochemical method for localization of estrogen receptors in rat tissues using a dinitrophenyl (DNP)-labeled rat monoclonal primary antibody. Journal of Histochemistry & Cytochemistry 38(1), pp. 69-78. (10.1177/38.1.1688451)

1988

Nicholson, R. I.et al. 1988. Actions of oestrogens and antioestrogens on rat mammary gland development: Relevance to breast cancer prevention. Journal of Steroid Biochemistry 30(1-6), pp. 95-103. (10.1016/0022-4731(88)90081-7)

PH3101 Optimisation of drug design
PH3114 Design, formulation and quality assurance of medicinal products
PH3202 Research methodology

Research interests

Anti‑hormone-induced signalling in ER + breast cancer.
Mechanisms of anti‑hormone and anti-growth factor resistant breast cancer growth and progression.
Novel target discovery and evaluation of new therapies using breast cancer cells in vitro.
(Signal transduction and biomarker studies in clinical cancer.

My research interests have principally been directed towards gaining a fuller appreciation of breast cancer biology, mechanisms of failure of anti‑hormonal agents and the associated gain of poorer prognosis. In my PhD, I used electron microscopy and immunocytochemistry to examine the impact of anti‑oestrogens on the normal breast. The studentship included optimising novel immunocytochemical procedures to monitor oestrogen receptor in breast cancer, a protein now routinely measured in the clinic. My subsequent postdoctoral positions focussed around monitoring signal transduction deregulation in clinical DCIS, and then in my position as Senior Research Associate for the Tenovus Centre for Cancer Research within invasive breast cancer, determining growth factor signal transduction underlying resistance to anti‑hormones and anti-growth factors in experimental models and clinical disease. The aim of these latter studies was not only to reveal novel drug failure biomarkers, but also new therapeutic targets including providing landmark data demonstrating the success of anti-EGFR therapy alongside anti‑hormones in ER+ breast cancer in vitro.

More recently, I have been interested in deciphering and evaluating targeting of oncogenic signalling induced by anti-hormones during the drug responsive phase of ER+ breast cancer that may limit maximal initial growth-inhibitory response. This novel research area, pioneered by our group, stemmed from our studies demonstrating compensatory induction of erbB signalling by antihormones and landmark data demonstrating the value of co-targeting induced EGFR alongside such agents in ER+ breast cancer. Our in vitro findings using multiple breast cancer models indicate the immense potential for targeting of compensatory signalling such as EGFR, HER2 and Src irrespective of genetic background, potentially further influenced by paracrine environment. Through such studies the aim is to reveal new signalling targets for pharmacological inhibitors that can be used in "intelligent" treatment combination strategies with anti-hormones to improve initial response and delay/prevent resistance. My Fellowship will now consider the ability of extended antihormonal exposure to radically re-programme ER+ breast cancer and will encompass in vitro and clinical breast cancer studies. As part of the Fellowship, I will also undertake training with Dr. Graham Ball, Reader in Bioinformatics at Nottingham Trent University. The Fellowship will deepen my resistance knowledge, enhance my bioinformatics skills, allow me to further flourish as an independent researcher in breast cancer and consolidate my team's reputation at the forefront of translational research in breast cancer.

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

Exploration of new targeted therapeutic agents in breast cancer models (e.g. Zactima; pan-erbB inhibitor; mTOR inhibitor
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.

Collaborators

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);

Key expertise

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

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.

Current Student

Ertefai, Benyamin

Goruchwyliaeth gyfredol

Robin Aske

Research student

Proffiliau allanol

ORCID

Dr Julia M.W. Gee

Trosolwg

Qualifications

Funding bodies which support our work

Bywgraffiad

Relationship with practitioners

Aelodaethau proffesiynol

Ymrwymiadau siarad cyhoeddus

Public engagement

Pwyllgorau ac adolygu

Cyhoeddiadau

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