Dr Paul Alexander Foster B.Sc., PhD

Dr Paul Alexander Foster

Institute of Metabolism and Systems Research
Lecturer in Cancer Endocrinology

Contact details

Address
College of Medical and Dental Sciences
Institute of Metabolism and Systems Research
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Paul leads the Steroid Metabolism in Cancer Research group at the University of Birmingham. He is an established research figure in the endocrinology and cancer fields. With over a decade of experience in both academic and industrial environments, he has extensive research knowledge on a wide-range of areas. He is an author on over 40 scientific peer-reviewed papers, covering endocrinology, oncology, inflammation, cardiology, and drug development, and has various reviews and book chapters to his name.

Paul’s primary research focus centres around steroid metabolism, with a particular interest in the sulfation and desulfation of sex steroids. His work has been integral to the development of various new drugs for the treatment of breast and prostate cancer.

Paul is an enthusiastic scientist who communicates his academic research on endocrine-related cancers at national and international conferences. He is extremely interested in the identification and targeting of pathways within steroidogenesis in order to develop new treatments for hormone-dependent disease.

Qualifications

Lecturer in Molecular Endocrinology:

  •  PhD in Pharmacology, King’s College London
  • BSc in Physiology and Pharmacology, University of Nottingham

Biography

Paul qualified with a B.Sc. (Hons) in Physiology and Pharmacology. He subsequently went on to do a Ph.D. in Pharmacology at King’s College London, where his research focused on the role of nerve growth factor (NGF) as an inflammatory and pain mediator.

Paul remained in the inflammatory field when he took a research associate position at Queen Mary University London. His primary research areas at that time concentrated on how the kinins, particularly bradykinin, protected against cardiac ischemia/reperfusion injury (I/R). At this time Paul also gained teaching experience as a lecturer on various BMedSci courses.

Paul moved into investigating endocrine-related cancer at Imperial College London and Sterix Ltd. (a spin-out company own by Ipsen Pharmaceuticals Ltd.). There he was fortunate to work with Prof Michael Reed and Dr Alan Purohit, key leaders in the field of steroid metabolism. Direction of research focused on two main areas, 1) the development of novel enzyme inhibitors for the treatment of hormone-driven cancers and, 2) the development of novel cytotoxic/anti-angiogenic agents for hormone-refractory cancers. Both research themes resulted in significant successes with various compounds in or about to enter clinical trials. Paul directed all in vivo research at Sterix Ltd. This primarily involved the design and development of novel animal models of hormone-driven cancer to allow drug proof of concept studies. These models have become integral to the pre-clinical development of a number of anti-cancer agents and have informed future clinical drug trials.

Paul then joined the University of Birmingham as a non-clinical Lecturer in Molecular Endocrinology and his work builds on his previous experiences. His research team focuses on:

1)      Oestrogen metabolism and signalling in the development and proliferation of colorectal cancer.

2)      Understanding sex steroid sulfation and desulfation pathways in normal and malignant physiology.

3)      Identifying new compounds that inhibit sex steroid metabolism as novel treatments for hormone-dependent cancers.

4)      Protein disulfide isomerise inhibitors for the treatment of cancer.

Teaching

Programme and Module Roles:
Module Lead – MBChB1 – Cell Communications, Endocrinology, Pharmacology (CEP)

Module Lead – MSc Drug IP and Commercialisation
Module Lead – BDS Endocrine


Deputy Module Lead – BDS1 Digestion, Reproduction, and Endocrine

Other teaching commitments:
BMedSci 3rd year – Endocrinology of Common Metabolic Disorders

MSc. Translational Medicine – Drug Development
MPharm HDT 1-2 – Pathophysiology of bone, Parathyroid and calcium regulation
BClin Sci (Intercalating) – New Drugs for Breast Cancer

Postgraduate supervision

Paul is always interested in recruiting talented new PhD students and postdoctoral associates. Please feel free to contact him for further information on current opportunities. If you are interested in furthering your studying in endocrine-related cancers or drug discovery please contact Paul on the contact details above, or for any general doctoral research enquiries, please email: dr@contacts.bham.ac.uk or call +44 (0)121 414 5005.

For a full list of available Doctoral Research opportunities, please visit our Doctoral Research programme listings.

Research

Research Themes

Endocrinology, Oncology, Oestrogen Metabolism, Colorectal Cancer, Breast Cancer, Metabolic inhibitors, Novel in vivo Cancer Modelling.

See www.drpaulfoster.co.uk

Oestrogen metabolism and signalling in colorectal cancer

Uncertainty surrounds the actions of oestrogens in colorectal cancers (CRC). Although epidemiological evidence suggests that oestrogens are protective against this malignancy, there is now significant research demonstrating oestrogen action may increase the incidence and proliferation of colorectal cancer. What is clear is that the regulation of oestrogen synthesis and metabolism is important in CRC. Numerous studies indicate that oestrogen receptor b (ERb), which when activated induces apoptosis,  is lost during colonic tumourigenesis. We have shown that steroid sulfatase (STS), an enzyme which desulfates conjugated oestrogens to their active forms, is elevated in CRC. Indeed, increased STS activity is related to increased CRC proliferation. It has also been demonstrated that down-regulation of 17b-HSD-2, which oxidises oestradiol (E2) to oestrone (E1), has also been shown to be a negative prognostic factor for CRC mortality, and the ratio between STS and sulfotransferase (SULT1E1), enzymes that de-sulfate and sulfate E1 respectively, is a potent prognostic factor for CRC clinical outcomes. However, much remains unclear due to a lack of basic molecular research. For example, although the STS/EST ratio in CRC patient tissue has implications on mortality, it is unknown how this effects CRC cell growth, E1S/E1/E2 concentrations, and ERa/ERb expression in vitro and in vivo. Furthermore, complete profiling of oestrogenic enzyme expression and activity, which would allow a greater understanding of local oestrogen concentrations, is lacking in available CRC cell lines and patient samples. This information, once ascertained, would clarify how oestrogens influence CRC, potentially leading to new therapeutic avenues for this disease.

Identifying novel inhibitors of oestrogen metabolism

We work with various worldwide research groups on the identification of novel pharmacological inhibitors that block oestrogen metabolism. We provide key assays (Steroid Sulfatase, Sulfotransferase, Aromatase) to identify potent inhibitors of these enzymes. We anticipate these inhibitors will be useful for the treatment of oestrogen-dependent cancers.

Unravelling the steroid metabolome in ovarian cancer

We are in the early stages of identifying potential early detection diagnostic tests for ovarian cancer. Early detection of this malignancy is key to improving patient survival rates. Thus, we are examining the steroid profile of ovarian cancer tissue and of the patients’ urine and serum to identify novel biomarkers for the disease.

Research groups and Centres

Institute of Metabolism and Systems Research

Twitter: @drpaulfoster

Linkedin: https://www.linkedin.com/in/drpaulfoster/

Website: www.drpaulfoster.co.uk

 

University of Birmingham collaborators:

-       Prof Wiebke Arlt

-       Dr Rowan Hardy

-       Dr Jonathan Mueller

-       Dr Sudha Sundar

-       Dr Andrew Beggs

-       Dr Liam Cox

-       Dr Angela Taylor

-       Dr Dan Tennant

-       Dr Vas Chortis

-       Dr David Jeevan

National collaborators:

-       Prof Barry Potter (University of Oxford)

-       Dr Atul Purohit (Imperial College London)

-       Dr Douglas Gibson (University of Edinburgh)

-       Prof Philippa Saunders (University of Edinburgh)

-       Dr Christopher Ireson (Pharmidex Ltd.)

-       Prof Lou Metherill (Queen Mary’s University, London)

International collaborators:

-       Prof Ulrike Grienke (University of Vienna, Austria)

-       Prof Judith Rollinger (University of Austria)

-       Dr Mohammad El-Gamal (University of Sharjah, UAE)

-       Dr Mark-Henry Pitty (Oregon Therapeutics, Paris, France)

Other activities

Institute of Metabolism and Systems Research:

  • Post-graduate Research Lead
  • Communications Lead

Editorial Board Member:

  • BMC Cancer
  • Endocrine Connections
  • Open Enzyme Inhibition Journal

Publications

Chortis V, Taylor AE, Doig CL, Walsh MD, Meimaridou E, Jenkinson C, Rodriguez-Blanco G, Ronchi CL, Jafri A, Metherell LA, Hebenstreit D, Dunn WB, Arlt W, Foster PA (2018) Nicotinamide Nucleotide Transhydrogenase as a Novel Treatment Target in Adrenocortical Carcinoma. Endocrinology. 159(8):2836-2849.

Foster PA, Mueller JW. (2018) SULFATION PATHWAYS: Insights into steroid sulfation and desulfation pathways. J Mol Endocrinol. 61(2):T271-T283.

Gibson DA, Foster PA, Simitsidellis I, Critchley HOD, Kelepouri O, Collins F, Saunders PTK. (2018) SULFATION PATHWAYS: A role for steroid sulphatase in intracrine regulation of endometrial decidualisation. J Mol Endocrinol. 61(2):M57-M65.

Dohle W, Jourdan FL, Menchon G, Prota AE, Foster PA, Mannion P, Hamel E, Thomas MP, Kasprzyk PG, Ferrandis E, Steinmetz MO, Leese MP, Potter BVL. (2018) Quinazolinone-Based Anticancer Agents: Synthesis, Antiproliferative SAR, Antitubulin Activity, and Tubulin Co-crystal Structure. J Med Chem. 61(3):1031-1044.

Meimaridou E, Goldsworthy M, Chortis V, Fragouli E, Foster PA, Arlt W, Cox R, Metherell LA. (2018) NNT is a key regulator of adrenal redox homeostasis and steroidogenesis in male mice. J Endocrinol. 236(1):13-28.

Gilligan LC, Rahman HP, Hewitt AM, Sitch AJ, Gondal A, Arvaniti A, Taylor AE, Read ML, Morton DG, Foster PA. (2017) Estrogen Activation by Steroid Sulfatase Increases Colorectal Cancer Proliferation via GPER. J Clin Endocrinol Metab. 1;102(12):4435-4447.

Gilligan LC, Gondal A, Tang V, Hussain MT, Arvaniti A, Hewitt AM, Foster PA. (2017) Estrone Sulfate Transport and Steroid Sulfatase Activity in Colorectal Cancer: Implications for Hormone Replacement Therapy. Front Pharmacol. 8:103.

Rahman HP, Hofland J, Foster PA. (2017) In touch with your feminine side: how oestrogen metabolism impacts prostate cancer. Front Pharmacol. 8:103.

Mueller JW, Gilligan LC, Idkowiak J, Arlt W, Foster PA. (2015) The Regulation of Steroid Action by Sulfation and Desulfation Endocr Rev. 36(5):526-63.

Stengel C, Newman SP, Day JM, Chander SK, Jourdan FL, Leese MP, Ferrandis E, Regis-Lydi S, Potter BV, Reed MJ, Purohit A, Foster PA. (2014) In vivo and in vitro properties of STX2484: a novel non-steroidal anti-cancer compound active in taxane-resistant breast cancer. Br J Cancer. 111(2):300-8.

For a full list of Dr Paul A Foster's publications

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