Theresa Hickey

Associate Professor Theresa Hickey

Externally-Funded Research Fellow (D)

Adelaide Medical School

Faculty of Health and Medical Sciences

Eligible to supervise Masters and PhD - email supervisor to discuss availability.

Associate Professor Theresa Hickey is the Scientific Program Leader of the Dame Roma Mitchell Cancer Research Laboratories (DRMCRL), Adelaide Medical School, University of Adelaide and a current National Breast Cancer Foundation Research (NCBF) Fellow.

She is internationally recognised for her research on sex hormone action in female reproductive tissues and disorders, with specific expertise in breast cancer. Theresa has pioneered new treatment strategies for breast cancer and established a patient-derived ex vivo culture methodology as a powerful new pre-clinical tool for drug development. Her group’s innovative work in this area has attracted substantial national and international interest in using the ex vivo culture technique as a pre-clinical model in several different tumour types.

Since award of her PhD on androgen receptor (AR) signalling in polycystic ovary syndrome (PCOS) from the University of Adelaide in 2006, Theresa has received continuous funding by nationally and internationally competitive grants and fellowships (NHMRC, US DoD, RAHRC, NBCF). Her current research focuses on AR signalling in human breast biology and breast cancer and extends into the field of prostate cancer, leveraging similarities between these two hormone-driven cancers to forge new insights that may benefit patients of either disease. Theresa has expertise in contemporary techniques for whole genome interrogation of transcription factor chromatin binding (ChIPseq, ChIPexo) and novel proteomic techniques to interrogate protein interactions (RIME; qPLEX-RIME) and is committed to translational research by developing and employing model systems that use patient-derived material to maximize clinical relevance (PDX, MIND xenografts).

Theresa is passionate about community engagement, enjoys sharing her team’s work through the media or via active interaction with patients and consumer advocates to develop collaborative partnerships. She was instrumental in establishing a core group of consumer advocates that advise and inform DRMCRL research and is an active member of the South Australia Breast Cancer Study Group (SABCSG). This group brings together people working in all facets of breast cancer (e.g. surgeons, radiologists, nurses, researchers, oncologists, genetic counsellors) to improve patient outcomes.

The Dame Roma Mitchell Cancer Research Laboratories (DRMCRL) have an international reputation for research into sex hormone action in hormone-dependent cancers, with a particular emphasis on breast and prostate cancers.

This world-class cancer research centre brings together expertise spanning more than 30 years in basic and translational prostate and breast cancer research. It is the leading centre in Australia with a multidisciplinary team of scientists, clinicians and patient advocates dedicated to understanding how sex hormones and their receptors control tumour behaviour in both disease contexts. The information is used to understand mechanisms of resistance to existing hormonal therapies for breast and prostate cancer and in developing new strategies for disease treatment and management. Research programs span discovery, drug development and clinical translation.

A major research focus at the DRMCRL is the development of novel androgen receptor (AR) targeted therapies for breast and prostate cancer. In prostate cancer, this involves the generation of drugs to inhibit aberrant forms of the AR that drive the disease and are unresponsive to conventional androgen deprivation therapies. In breast cancer, our research has led to new strategies to activate the AR as well as the progesterone receptor (PR) to inhibit growth of tumours that are driven by the estrogen receptor (ER), This includes interrogation of Selective Androgen Receptor Modulators (SARMs), compounds that lack masculinizing action in women but are able to stimulate AR activity in select tissues. Our breast cancer research program also investigates AR action in the context of breast cancers that lack ER to determine what is the optimal approach for targeting AR in this context.

Our laboratory has pioneered integration of genomic technologies with unique preclinical models of human breast and prostate cancers, especially patient-derived explant cultures, xenograft and organoid models, to better understand disease mechanisms and facilitate translation of breast and prostate cancer research into the clinic.

We publish in high impact journals such as Nature, Nature Genetics, Nature Reviews Cancer, Cancer Research, Clinical Cancer Research and Oncogene. Our research is well supported by funding from nationally and internationally competitive grants. The DRMCRL offers students a wide array of projects that span cutting-edge biomedical research using contemporary pre-clinical models, genome-wide technologies and access to large proteomic/genomic databases.

We are currently actively seeking students interested in bioinformatics to interrogate these databases, with opportunities of cross faculty supervision in fields such as mathematics and machine learning.

 

Key Research Projects Available for DRMCRL

Project 1 - Transforming endocrine therapy for breast and prostate cancer

Description -  Breast and prostate cancers are diseases driven by abnormal sex hormone receptor activity mediated by the estrogen receptor (ER) in breast and the androgen receptor (AR) in prostate cancers. Surgery and radiation therapy for these diseases work well when the tumour is confined within the organ of origin. However, for cancers that have spread out of the breast or prostate, either locally or to other parts of the body, the major treatment strategy is to completely abolish the activity of the offending sex hormone receptor. This treatment strategy is called hormone deprivation therapy and has been employed for the past century. Overwhelming evidence indicates that hormone deprivation therapy has run its course in providing a survival advantage to people with breast or prostate cancer.

Our hypothesis is that reprogramming estrogen or androgen receptors (ER and AR) away from oncogenic activity toward more benign activity will transform endocrine therapy for breast and prostate cancer. In this project we aim to discover optimal strategies to reprogram ER or AR activity in breast and prostate cancer by investigating three complementary approaches to reprogramming ER/AR: 1) Activate other nuclear receptors that directly inhibit ER/AR signalling; 2) Utilize selective ER/AR ligands; and 3) Enhance ER/AR reprogramming with epigenetic drugs. We will then validate optimal reprogramming strategies in patient-derived xenograft “clinical trials” and clinical samples.

Available for: Honours and HDR

Start Date: Semester 1 and 2 2023 

 

Project 2 - Selective activation of androgen receptor to treat estrogen receptor positive breast cancer

Description - Androgens, acting via the androgen receptor (AR), a protein related to the estrogen receptor (ER), are natural inhibitors of estrogen-stimulated breast cancer growth. Although androgens are commonly considered to be male hormones, females produce androgens throughout their life. AR typically is present in the same cells as ER, resulting in estrogen and androgen hormones exerting opposing forces on the growth of ER-positive breast cancers, with estrogen having growth promoting and androgens protective effects.



The goals of this project are: 1) Investigate how stimulation of the androgen receptor (AR) by a synthetic androgen which has been shown to be well tolerated by women, inhibits the growth of estrogen-sensitive breast tumours; and 2)  Develop and evaluate proteins identified as being potential biomarkers of response to androgenic therapies.

Available for: Honours and HDR

Start Date: Semester 1 and 2 2023

 

Project 3 -  The clinical significance of sex hormone crosstalk in estrogen receptor positive breast cancer

Description - Breast cancer is mainly a disease in which the sex hormone estrogen stimulates uncontrolled growth via the estrogen receptor (ER). We have recently discovered that other sex hormones, including progesterone and androgen, can redirect the actions of estrogen in breast cancers to halt growth or make a tumour disappear. This project will examine the complex interaction between all three sex hormones to develop new, more effective strategies for treating breast cancer.

In this project, we will investigate the three-way interplay between ER, PR (progesterone receptor) and AR (androgen receptor) in contemporary models of breast cancer including patient derived xenografts and ex-vivo cultured primary tumour tissues. The ultimate goal is to determine clinical scenarios in which PR, AR or both could be optimally therapeutically targeted to treat ER+ breast cancer, particularly disease resistant to current ER targeting drugs.

Available for: Honours and HDR

Start Date: Semester 1 and 2 2023

 

Project 4 - Pushing AR toward better outcomes in breast and prostate cancers

Description - This project will establish the efficacy of drugs called SARMs (selective androgen receptor modulators) for re-activating the normal, non-oncogenic function of the AR (androgen receptor) in human-derived pre-clinical models and clinical samples of breast and prostate cancers. Currently available SARMs (eg Enobosarm) have excellent safety profiles, and are poised for rapid implementation into clinical trials. Through our collaborations with clinicians that currently run breast cancer and prostate cancer clinical trials, we have access to breast cancer and prostate cancer samples, and also an avenue to prepare them to quickly implement novel treatment strategies that arise from this project.

The aims of this project are: 1) Identify SARMs that reprogram AR from oncogenic to benign genomic loci in breast cancers and prostate cancers; 2) Identify proteins that mediate AR reprogramming in breast and prostate cancers; 3) Pre-clinically test selected SARMs with therapeutic potential; and 4) Determine the clinical scope for SARMs and candidate biomarkers derived during the project. 

Available for: Honours and HDR

Start Date: Semester 1 and 2 2023

 

Project 5 - Targeting CDK9 in triple negative and endocrine-resistant breast cancers

Description - Triple negative breast cancer (TNBC) is the worst form of breast cancer at diagnosis. Better treatments for these cancers is a critical unmet need. TNBC preferentially afflicts young women and those with mutations of the BRCA1 gene. Another very aggressive form of breast cancer is estrogen receptor (ER) driven cancer that becomes resistant to ER targeting therapies. Chemotherapy and more recently, CDK4/6 inhibitors are the only approved means of treating these cancers, but survival rates remain low.

This project focuses on these highly aggressive breast cancers that collectively cause the majority of breast cancer-related death.  Such cancers have phenomenal rates of growth, in part due to elevated transcriptional activation of oncogenes. In collaboration with a medicinal chemist (Prof Shudong Wang), we are testing new drugs that specifically target CDK9, a factor that can ramp up the transcriptional activity of RNA polymerase II.  The goals of this project are: 1) Demonstrate the efficacy of novel CDK9 inhibitors in a unique suite of patient-derived xenograft models of triple negative and endocrine-resistant breast cancer; 2) Identify cellular mediators of CDK9-targeted therapy in these disease subtypes; and 3) Test our CDK9 inhibitors in prospectively-collected patient derived explant tumours cultured ex vivo and evaluate a biomarker signature of treatment response.

Available for: Honours and HDR

Start Date: Semester 1 and 2 2023

  • Appointments
    Date Position Institution name
    2019 - 2023 National Breast Cancer Foundation Fellow, Dame Roma Mitchell Cancer Research Laboratories University of Adelaide
    2015 - 2018 Royal Adelaide Hospital (RAH) Research Foundation 2015 Florey Fellow University of Adelaide
    2011 - 2015 US Department of Defence Breast Cancer Early Career Research Fellow University of Adelaide
    2007 - 2010 Peter Doherty NHMRC Post-doctoral Research Fellow (Academic Level B; Step 2) Interdisciplinary project between the Research Centre for Reproductive Healthy and the Department of Medicine, Hanson Institute/IMVS/University of Adelaide
    2006 - 2006 Postdoctoral Research Scientist University of Adelaide
    1998 - 2006 Senior Research Officer University of Adelaide
    1997 - 1997 Research Officer University of Adelaide
    1991 - 1996 NHMRC Research Assistant Flinders University

  • Awards and Achievements
    Date Type Title Institution Name Country Amount
    2018 Award Best Scientific Presentation Award SA Breast Cancer Research Day Australia -

  • Education
    Date Institution name Country Title
    2006 The University of Adelaide Australia PhD in Medicine
    1999 The University of Adelaide Australia Masters Qualifying Year (Hons equivalent)
    1982 Arcadia University United States BA in Biology

  • Research Interests
    Cancer Cell Biology Cancer Genetics Cancer Therapy Cancer Biology and Clinical Oncology

Chief Investigator: Cancer Australia Arming androgen receptors to transform endocrine therapy for ER+ breast cancer (2023-2025; $599,600) 

Chief Investigator: NBCF Investigator Initiated Research Scheme Targeting the hormone-immune cell axis to prevent breast cancer progression (2023-2026; $868,191) 

Associate Investigator: NBCF Investigator Initiated Research Scheme Is AR activation the key to stopping breast cancer metastasis? (2023-2026; $1,158,986)

Associate Investigator: NHMRC Ideas Grant Exploiting sex differences in androgen action to advance a novel treatment for breast cancer. (2023-2026; $1,262,967)

Chief Investigator: NBCF Investigator Initiated Research Scheme Reprogramming the estrogen receptor to eradicate endocrine-resistant breast cancer. (2022-2026; $788,944)

Chief Investigator: Cancer Council SA Beat Cancer A new endocrine paradigm to target metastasis of estrogen receptor positive breast cancer (2023; $75,000)

Associate Investigator: NHMRC Ideas Grant A combinatorial drug strategy to target lethal forms of breast cancer (2020-2023; $1,148,310)

Chief Investigator: NBCF Investigator Initiated Research Scheme Targeting CDK9 in triple negative and endocrine-resistant breast cancers (2019-2023; $837,547)

Chief Investigator: Movember and NBCF Breast and Prostate Cancer Linkage Grant Transforming endocrine therapy for breast and prostate cancer (2018-2021; $2,500,000)

Chief Investigator: THRF Infrastructure Support Grant Transforming therapy for breast and prostate cancer (2018-2021; $375,000)

Chief Investigator: NHMRC Project Grant Pushing AR toward better outcomes in breast and prostate cancers (2018-2021; $998,754)

Chief Investigator: Princess Alexander Hospital Research Fund Project Grant Translation of the Pathobiology and Portable, MRI-based Quantification of Mammographic Density (MD) for Improved Breast Cancer Prevention and Treatment (2018-2019)

Chief Investigator: NHMRC Project Grant The clinical significance of sex hormone crosstalk in estrogen receptor positive breast cancer (2017-2020; $1,023,132)

Associate Investigator: Emerald Clinical Trial (2016-2018; $200,000 GBP)

Chief Investigator: Cancer Australia Project Grant A novel approach to overcome therapy-resistance in breast cancer (2016-2018; $600,000 AUD)

Chief Investigator: GTx Inc. Project Grant Enobosarm for women with breast cancer: investigating the scope and mechanstic basis of therapeutic efficacy (2016-2017; $455,078 USD)

Sole Chief Investigator: Royal Adelaide Hospital Research Foundation Career Development Fellowship Selective activation of the Androgen receptor as a novel therapeutic strategy for breast cancer (2015-2017; $348,000)

Chief Investigator: NHMRC Project Grant Selective activation of androgen receptor to treat estrogen receptor positive breast cancer (2015-2017; $816,924)

2017 Early Career Mentor: Centre for Cancer Biology (CCB), University SA

  • Current Higher Degree by Research Supervision (University of Adelaide)
    Date Role Research Topic Program Degree Type Student Load Student Name
    2023 Principal Supervisor Role of Androgen Receptor Signalling in the Metastasis of Estrogen Receptor Positive Breast Cancer Doctor of Philosophy Doctorate Full Time Ms Dana Basem Mohamad Al Safadi
    2023 Co-Supervisor Investigating the role of androgen receptors in bladder cancer Doctor of Philosophy Doctorate Full Time Mr Ahmed Faris Abdulridha Aldoghachi
    2023 Co-Supervisor How Cancer Associated Fibroblasts Modify Stromal Landscape to Advance Malignant Progression of Breast Cancer Doctor of Philosophy Doctorate Full Time Mr Michael Antoniou
    2023 Co-Supervisor The biological function of tryptophan metabolism in triple-negative breast cancer and cancer stem cells population Doctor of Philosophy Doctorate Full Time Mr Jamshid Motalebzadeh
    2022 Principal Supervisor An Innovative Treatment Strategy for Hormone-Dependent Cancers Doctor of Philosophy Doctorate Full Time Ms Maliha Wajahat .
    2021 Co-Supervisor Exploring the Role of Steroid Receptors in ER+ Breast Cancer Doctor of Philosophy Doctorate Full Time Mr Alex Adrian Pace

  • Past Higher Degree by Research Supervision (University of Adelaide)
    Date Role Research Topic Program Degree Type Student Load Student Name
    2017 - 2021 Principal Supervisor Role of the GATA3 Transcription Factor on AR Signalling in Breast Cancer Doctor of Philosophy Doctorate Full Time Mrs Leila Hosseinzadeh
    2017 - 2021 Principal Supervisor Development of a Novel Therapeutic Strategy for Estrogen Receptor Negative Breast Cancer Doctor of Philosophy Doctorate Full Time Mrs Ebtihal Hashem Mustafa
    2016 - 2020 Co-Supervisor The Role of MicroRNA-194 in Prostate Cancer Progression Doctor of Philosophy Doctorate Full Time Miss Rayzel Candida Fernandes
    2010 - 2016 Principal Supervisor The Role of Estrogen Receptor and the Androgen Receptor in Human Breast Cancer Doctor of Philosophy Doctorate Part Time Mrs Shalini Jindal
    2009 - 2013 Principal Supervisor Investigation into the Expression and Localisation of C-Kit and the Regulation of Kit Ligand Gene Expression in the Adult Human Ovary Doctor of Philosophy Doctorate Full Time Dr Astrud Tuck
    2008 - 2012 Principal Supervisor The Molecular Actions of Medroxyprogesterone Acetate on Androgen Receptor Signalling and the Promotion of Breast Cancer Doctor of Philosophy Doctorate Full Time Miss Aleksandra Ochnik
    2008 - 2012 Principal Supervisor The Role of Small Glutamine-Rich Tetratricopeptide Repeat Containing Protein Alpha in Female Reproductive Tissues Doctor of Philosophy Doctorate Full Time Ms Miriam Simone Butler

  • Committee Memberships
    Date Role Committee Institution Country
    2019 - ongoing Advisory Board Member Program Organising Committee 7th PacRim International Breast & Prostate Cancer Meeting Australia
    2017 - ongoing Advisory Board Member Human Ethics Committee Bellberry Ltd Australia
    2015 - ongoing Advisory Board Member Executive Committee SA Breast Cancer Study Group Australia

  • Memberships
    Date Role Membership Country
    2015 - ongoing Advisory Board Member South Australia Breast Cancer Study Group Australia
    2005 - ongoing Member Australian Women in Endocrinology Australia
    2002 - ongoing Member Endocrine Society of Australia Australia
    2002 - ongoing Member The Endocrine Society (USA) Australia

  • Presentation
    Date Topic Presented at Institution Country
    2021 - 2020 Invited Presentation: Targeting the androgen receptor in breast cancer 5th Australian Translational Breast Cancer Research Symposium Garvan Institute of Medical Research, Sydney, NSW Australia
    2020 - ongoing Invited Presentation: Androgen receptor signalling trans-represses estrogen receptor signalling in breast cancer Cancer Seminar Series Virtual Translational Research Institute (QLD) Australia

  • Review, Assessment, Editorial and Advice
    Date Title Type Institution Country
    2019 - ongoing Editor Journal Review Journal of Investigative Medicine, United States
  • Position: Externally-Funded Research Fellow (D)
  • Phone: 83137858
  • Email: theresa.hickey@adelaide.edu.au
  • Campus: North Terrace
  • Building: Adelaide Health and Medical Sciences, floor 8
  • Org Unit: Medical Specialties
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