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Dr Julia M.W. Gee

Dr Julia M.W. Gee

Senior Lecturer

School of Pharmacy and Pharmaceutical Sciences

Users
Available for postgraduate supervision

Overview

Overview

I joined Cardiff School of Pharmacy & Pharmaceutical Sciences in 2000 and following my Breast Cancer Now Fellowship was appinted in 2015 as a Senior Lecturer in the School. My research in the Breast Cancer Molecular Pharmacology group focusses on understanding therapeutic response and failure in breast cancer, particularly in relation to anti-hormonal treatments that inhibit oestrogen receptor signalling and further targeted therapies. My research  uses unique experimental cell models that we have developed in the School to mimic resistance, as well as patient tumour samples.

Our group spearheaded the concept that such cancer treatments can actively-induce compensatory proliferative and cell survival signalling pathways in breast cancer which limit their therapeutic value and drive development of resistance, and I am currently  interested in exploring the loss of oestrogen receptor and the gains in alternative signalling that can occur after long-term anti-hormone treatment. Several mechanisms not previously linked to anti-hormone resistance are emerging from the signalling studies. This work is important because resistance develops in at least a third of  breast cancer patients and remains an area largely of unmet clinical need in this disease. Our goal in deciphering these mechanisms is to  reveal potential approaches to target anti-hormone resistance and its aggressiveness in the future and also to discover possible biomarkers for resistant breast cancer.

Alongside these anti-hormone treatment studies, I am also interested in newer therapeutic avenues that may be of future value in breast cancer - for example, we are currently evaluating photo-dynamic therapy sensitivity in different breast cancer subtypes using cell models. Drawing on my  immunohistochemical expertise, I  have also undertaken key translational biomarker studies for several national breast cancer new agent trials in collaboration with clinical colleagues. These have previously included immunohistochemistry for studies with the anti‑hormone Fulvestrant in breast cancer (e.g. Study 41 and NEWEST trials) and most recently for novel targetted signal transduction inhibitor studies (e.g. FURVA and STAKT trials), with some of these studies using patient samples taken sequentially during  treatment response and relapse.

I am a member of the School's research theme:

Drug Discovery, Pharmaceutical Sciences and Experimental Therapeutics (DDPSET)

Biography

I received a BSc (Hons) in 1985 in Physiological Sciences from the University of Newcastle-Upon-Tyne. I then undertook a Medical Research Council-funded PhD studentship at the University of Wales College of Medicine in the breast cancer laboratory of the then Tenovus Institute (PhD awarded 1991) examining the impact of anti‑oestrogens on the normal breast.

Following my PhD, I held 3 consecutive postdoctoral breast cancer research positions in the Tenovus Institute between 1991-2000 (including one with Dept. Surgery, University of Wales College of Medicine examining pre-neoplastic clinical DCIS), becoming a Senior Postdoctoral 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 group within Cardiff School of Pharmacy and Pharmaceutical Sciences, focussing on resistance and  progression in breast cancer. Alongside contributing to the management of the Tenovus group, my role was to oversee its Clinical Immunocytochemistry Team, extending to analysing signalling elements using activation-specific antibodies in several Phase II breast cancer trials.  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. I also co-ordinated Gene Discovery in the group, applying microarrays and bioinformatics to reveal new signalling in resistant breast cancer models. I was funded until Sept. 2010 as Principal Investigator on a Tenovus Charity programme grant investigating how to improve treatment response in ER+ breast cancer cells.

I was then awarded a  prestigious 5-year Breast Cancer Now (then Breast Cancer Campaign) Scientific Fellowship (2010-2015) based in Cardiff  School of Pharmacy and Pharmaceutical Sciences, to develop new cell models and to use these to examine the impact of prolonged anti-hormone exposure on the acquired resistant phenotype in ER+ disease. Thereafter, I was appointed in 2015 as a Senior Lecturer in the School, where my research interests currently focus on anti-hormone-induced oestrogen receptor loss and gain of alternative adverse signalling in breast cancer models, biomarker studies in clinical breast cancer, and most recently exploring photo-dynamic therapy sensitivity of different breast cancer subtypes.

A significant part of my Senior Lecturer role also involves contributing to the design/management, teaching delivery, and assessment for the School's highly-successful taught Masters in Cancer Biology & Therapeutics programme, as well as contributing to teaching on the School's MPharm course in the areas of cancer treatment and reproductive endocrinology.

Qualifications

  • BSc. (Honours) in Physiological Sciences, University of Newcastle-Upon-Tyne, 1985
  • PhD. in breast cancer biology, University of Wales College of Medicine, 1991

Honours and awards

  • Gold medal, 9th World Congress on Advances in Oncology/7th International Symposium on Molecular Medicine, for my group's microarray and bioinformatic research in resistant breast cancer cells (2002)

Professional memberships

  • Invited British Breast Group Member and Programme Committee Chair

Academic positions

  • 2015- present:  Senior Lecturer, Cardiff School of Pharmacy & Pharmaceutical Sciences, Cardiff University
  • 2010-2015:       Breast Cancer Now Scientific Fellow, Breast Cancer Molecular Pharmacology Group, Cardiff School of Pharmacy & Pharmaceutical Sciences, Cardiff University
  • 2000-2010:       Senior Research Associate, Tenovus Centre for Cancer Research, Welsh School of Pharmacy, Cardiff University
  • 1993-1999:       Postdoctoral Researcher, Tenovus Centre for Cancer Research, University of Wales College of Medicine
  • 1991-1993:      Junior Postdoctoral Research Fellow (interdisciplinary award between Tenovus Cancer Research Centre &  Dept. Surgery), University of Wales College of Medicine
  • 1988-1991:      Research Technician, Tenovus Cancer Research Centre, University of Wales College of Medicine

Speaking engagements

Public engagement: 

  • Interaction with Breast Cancer Now and further cancer charities, speaker for fundraising groups/patient groups
  • Regular contributor to STEM events, focussing on cancer

Committees and reviewing

Current roles & committee membership in the School, College and University: 

  • Member, School Taught Board of Studies
  • Member, School Board of Research Postgraduate Studies & Postgraduate Research Day Committee
  • Member, School Equality, Diversity and Inclusion Committee
  • Member, School Research Ethics Committee
  • School’s HTA Officer
  • Member, University BLS Human Tissue Research Governance Committee
  • Member, University BLS Data Strategy Group
  • Member, University BLS Public Engagement Network
  • Member, University Breast Multi-Disciplinary Research group
  • Reviewer, Cardiff University Biobank

Current external committee and reviewing roles:

  • Member of Tissue Bank Advisory Council and Chair of Tissue Access Committee for Breast Cancer Now (I have also contributed to the Charity's two previous Gap analysis initiatives, and am a previous Scientific Advisory Board member)
  • Programme Committee Chair, British Breast Group
  • UK-Interdisciplinary Breast Cancer Symposium Executive Board Member
  • Editorial Board/reviewer for several journals including BMC Cancer; J. Hormone Molecular Biology & Clinical Investigation,  Breast Cancer Research, Endocrinology, & for various funding bodies

Publications

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1988

Teaching

MPharm:

  • PH1124 Human Body Systems: lecturer for reproductive endocrinology
  • PH3101 Optimisation of Drug Design: lecturer for anti-hormonal agents in breast cancer
  • PH4116 Pharmacy Research Project:  research project supervisor (lab and non-lab research) and PH4116 module team member
  • Contribute to OSCE marking for MPharm years 1-4

MSc Cancer Biology & Therapeutics:

  • As a core Senior Lecturer for the taught MSc Cancer Biology & Therapeutics Masters programme, I contribute to design/management, delivery, and assessment for all PHT801 (Cellular & Molecular Biology of Cancer),  PHT802 (Translational Oncology & Therapeutics), PHT803 (Academic Research Skills), PHT804 (Research Methodology), PHT805 (Research Project) and PHT806 (Data analysis & bioinformatics) modules of the programme.
  • I am the PHT806 (Bioinformatics) module leader and also lead several units within PHT801 and PHT802
  • I am a supervisor for cancer research projects on PHT805 (lab and non-lab research).


External teaching:

  • University of Brighton PYM14 cancer special topic module: lecturer on bioinformatics for cancer biologists

Research areas:

  • Anti‑hormone-induced signalling and ER loss in ER+ breast cancer.
  • Mechanisms of anti‑hormone and anti-growth factor resistant breast cancer growth and progression.
  • Novel target discovery and pre-clinical evaluation of new therapies using breast cancer models.
  • Translational signal transduction and biomarker studies in clinical breast cancers

Research expertise:

  • Breast cancer & clinical and experimental anti-hormone resistance biology
  • Steroid receptor & growth factor receptor/kinase signal transduction;
  • Novel biomarker & target discovery
  • Clinical and experimental immunocytochemistry, including using phospho-specific antibodies.
  • Treatment-resistant cell models
  • Gene microarrays & associated bioinformatics.

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‑hormones on the normal breast. The studentship included optimising novel immunocytochemical procedures to monitor oestrogen receptor (ER) in clinical and experimental breast cancer, a protein that is now routinely measured in the clinic. My subsequent postdoctoral positions focussed around monitoring  oestrogen receptor and further signal transduction deregulation in clinical DCIS, and then in my position as Senior Research Associate for the Tenovus Centre for Cancer Research examining 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.

I subsequently became interested in deciphering and targeting the oncogenic signalling that is paradoxically induced by anti-hormones during the drug responsive phase of ER+ breast cancer which limits maximal initial growth-inhibitory response and aids emergence of resistance. This novel research area, pioneered by our Breast Cancer Molecular Pharmacology group in Cardiff School of Pharmacy & Pharmaceutical Sciences, stemmed from our studies demonstrating compensatory induction of erbB signalling by anti-hormones. The group's in vitro findings using breast cancer models indicated there was potential for targeting of compensatory signalling, with our landmark studies demonstrating the value of co-targeting induced EGFR, HER2 or Src alongside anti-hormonal agents in ER+ breast cancer. This work included many collaborations  with Industry on their cancer drug development programmes in resistant breast cancer cells. My Breast Cancer Now Scientific Fellowship subsequently allowed me to consider the ability of extended anti-hormonal exposure to radically re-programme ER+ breast cancer, encompassing in vitro and clinical breast cancer studies and revealing that ER loss could also occur as a direct consequence of such treatment. The Fellowship deepened my resistance knowledge, enhanced my bioinformatics skills, and allowed me to further flourish as an independent researcher in breast cancer, culminating in my appointment as a Senior Lecturer in the School. It also allowed development of a large panel of long-term anti-hormone resistant cell models from multiple ER+ phenoypes that comprise a major resource in our ongoing research and for our collaborative studies.

Current research interests:

1. Discovery of resistance mechanisms that are a consequence of prolonged anti-hormone treatment

Studies of acquired anti-hormone resistance in breast cancer commonly use relatively short-term (~12month) anti-hormone-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 studies indicate longer-term (~3year) acquired anti-hormone-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 prolonged adjuvant anti-hormone exposure prior to clinical relapse could thus be critical in promoting the resistance mechanism and phenotype. Novel pathways we are implicating in our research include HIPPO pathway signalling, an alternative signalling kinase that is also increased in resistant clinical breast cancer samples, and tetraspanin-like molecules. These mechanisms  are currently being explored in our long-term antihormone resistant cell models (including through microarray profiling and bioinformatics) and in clinical samples. By deciphering such mechanisms, the aim is to discover new therapeutic targets which could ultimately prove superior to delay or treat clinical breast cancer relapse. For example, we  have identified some drug combinations that appear able to partially-recover oestrogen receptor and so anti-hormone treatment sensitivity in our long-term resistant cell models with ER loss, findings that may ultimately have clinical relevance since about 15% of breast cancers also lose this receptor at relapse.

2. Investigation and exploitation of novel therapies, including in clinical breast cancers

Our group has a long track-record in collaborating with Industry and clinicians to examine novel drugs, both in our cell models and through our involvement in biomarker studies in breast cancer clinical trials. Our anti-hormone resistant model research has identified that components of RET signalling, including its GFR-alpha co-receptors, are deregulated in resistance. Such cells are reliant on this signalling and so can be very effectively targeted in the laboratory using RET inhibitors, while a further kinase commonly implicated in resistance is AKT that can also be successfully inhibited to control resistant cell growth. Recently our study of new cancer treatments has built further on these promising model system findings- we have undertaken translational (immunohistochemical) studies in breast cancer samples from the STAKT (AKT inhibitor) and FURVA (RET inhibitor) clinical trials that are exploring such signal transduction inhibitors.

My PhD student is also evaluating photo-dynamic therapy (PDT) sensitivity in a panel of cell models reflective of different breast cancer subtypes and alongside conventional treatments, in order to decipher PDT response and resistance mechanisms. This research should identify how to maximise impact of this further potential new therapeutic approach.

Current national and international research collaborators:

  • I have collaborations in Cardiff School of Pharmacy and Pharmaceutical Sciences with S Hiscox, K Taylor, E Kidd, and also P Prokopovich and C Simons
  • J Robertson (Professor of Surgery, Royal Derby Hospital), University of Nottingham
  • A Green (Breast Pathology Research Group, School of Medicine), University of Nottingham Biodiscovery Institute
  • R Clarkson (School of Biosciences, Cardiff University)
  • M Flint, School of Pharmacy and Biomolecular Science, University of Brighton
  • R Clarke & B Simoes, Breast Biology Group, Manchester Breast Centre, University of Manchester
  • C Ormandy, Cancer Biology, Garvan Institute of Medical Research, Australia
  • S Clark, Epigenetics Research Laboratory, Garvan Institute of Medical Research, Australia
  • M Milevskiy, The Walter and Eliza Hall Institute of Medical Research, Australia

Funding bodies & Industry that have supported our research:

  • Breast Cancer Now
  • Nottingham University
  • AstraZeneca
  • Velindre NHS Trust Charitable Funds

Supervision

I am interested in supervising PhD students in the areas of:

Breast Cancer research, specifically:

  • Understanding the signalling mechanisms of cancer treatment response and failure
  • Translational studes- discovery of new targets/biomarkers using cell models and examining these in clinical breast cancer samples (I have also co-supervised MD projects in these areas previously)

Current supervision in the research area of breast cancer:

  • I  am currently supervising PhD student Robin Aske for his project " Design, Synthesis And Biological Evaluation Of Polymer Therapeutics For Photodynamic Treatment In Different Breast Cancer Phenotypes".
  • I am also contributing to co-supervision of several further PhD projects including Zoe Hudson (MEDIC) on  "Investigation Of Biomarker Determinants Of Treatment Efficacy Of Fulvestrant And The Ret Inhibitor Vandetanib In Oestrogen Receptor Positive Breast Cancer" and Ahmed Eissa on "4th generation aromatase inhibitors for the treatment of breast cancer: design, synthesis, biochemical and molecular biology studies".
  • I also run breast cancer-focussed 3 month research projects for the MSc Cancer Biology and Therapeutics taught Masters programme in the School

Current supervision

Robin Aske

Research student

Past projects

Since 2014:

  • Main Supervisor for:
    • Benyamin Ertefai  "Resistance mechanisms during endocrine treatment in breast cancer" (awarded 2016)
    • Hayley Francies "Characterising response and resistance mechanisms to Faslodex in breast cancer" (awarded 2014)
  • Co-supervision for several students including:
    • Silvia Ziliotto "Understanding how targeting zinc transporters prevents the development of aggressive cancer"  (awarded 2019)
    • Jessica Davis (MEDIC) "Identification of novel anti-hormone induced pro-survival genes in oestrogen receptor-positive breast cancer cells" (awarded 2017)
    • Rebecca Bellerby: "The exploration of CD44 as a mediator of a drug resistant phenotype in ER+ breast cancer" (awarded 2015)