Dr Paul A. Foster BSc, PhD

Dr Paul Foster

Institute of Metabolism and Systems Research
Associate Professor in Cancer Endocrinology
Director of Education for the Department of Metabolism and Systems Science
Department of Metabolism and Systems Science Senior Tutor

Contact details

Address
College of Medicine and Health
Department of Metabolism and Systems Science
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Dr Foster is an established research figure in the fields of endocrinology, cancer and drug discovery. With over two decades 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 55 scientific peer-reviewed papers, covering endocrinology, oncology, inflammation, cardiology, and drug development, and has various reviews and book chapters to his name.

Dr Foster’s primary research focus centres around steroid metabolism, with a particular interest in the enzymes involved in the sulfation and desulfation of sex steroids. His work has been integral to the identification of new drug targets and the development of various new drugs for the treatment of breast, prostate, ovarian, colorectal, and adrenal cancers. He is extremely interested in the identification and targeting of pathways within steroidogenesis in order to develop new treatments for hormone-dependent disease.

Dr Foster is also an enthusiastic scientist and educator who communicates his academic research on endocrine-related cancers at national and international conferences. He also teaches across many programmes in the College of Medicine and Health, is the Director of Education for the Department of Metabolism and Systems Science, and Leads Cell Communications: Endocrinology and Pharmacology (CEP) for the MBChB programme.

LinkedIn account - www.linkedin.com/in/drpaulfoster/ 

Qualifications

Associate Professor in Cancer Endocrinology

  • HEFCE Associate Fellow, University of Birmingham
  • PhD in Pharmacology, King’s College London
  • BSs (Hons) in Pharmacology and Physiology

Biography

Dr Foster qualified with a BSc (Hons) in Physiology and Pharmacology. He subsequently went on to do a PhD 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.

Dr Foster 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, Dr Foster also gained teaching experience as a lecturer on various BMedSci courses.

Dr Foster 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 Professor 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. Dr Foster 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.

Dr Foster then joined the University of Birmingham as a non-clinical Lecturer in Cancer 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 – BDS Endocrine

Other teaching commitments

  • BMedSci 3rd year – Endocrinology of Common Metabolic Disorders
  • MPharm HDT 1-2 – Pathophysiology of bone, Parathyroid and calcium regulation
  • BClin Sci (Intercalating) – New Drugs for Breast Cancer

Postgraduate supervision

Dr Foster 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 Dr Foster on the contact details above, or for any general doctoral research enquiries, please email: mds-gradschool@contacts.bham.ac.uk

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. Paul's research group has 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

Dr Foster’s research group also works with various worldwide research groups on the identification of novel pharmacological inhibitors that block oestrogen metabolism. His group provides key assays (Steroid Sulfatase, Sulfotransferase, Aromatase) to identify potent inhibitors of these enzymes. The group anticipates these inhibitors will be useful for the treatment of oestrogen-dependent cancers.

Unravelling the steroid metabolome in ovarian cancer

Dr Foster’s research group is 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, the group 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

Other activities

Department of Metabolism and Systems Science:

  • Director of Education
  • Senior Tutor

 

Editorial Board Membership:

  • Endocrine Connections
  • Frontiers in Pharmacology

Publications

Recent publications

Article

Beevors, LI, Sundar, S & Foster, PA 2024, 'Steroid metabolism and hormonal dynamics in normal and malignant ovaries', Essays in Biochemistry. https://doi.org/10.1042/EBC20240028

Zaraei, S, Dohle, W, Anbar, HS, El-gamal, R, Leblond, B, Foster, P, Al-Tel, T, Potter, BVL & El-gamal, MI 2024, 'Synthesis, biological evaluation, and stability studies of raloxifene mono- and bis-sulfamates as dual-targeting agents  ', Bioorganic & Medicinal Chemistry. https://doi.org/10.1016/j.bmc.2024.117645

Foster, PA & Mueller, JW 2023, 'New structural insights provide a different angle on steroid sulfatase action', The Journal of Steroid Biochemistry and Molecular Biology, vol. 232, 106353. https://doi.org/10.1016/j.jsbmb.2023.106353

Warmington, E, Smith, G, Chortis, V, Liang, R, Lippert, J, Steinhauer, S, Landwehr, L-S, Hantel, C, Kiseljak-Vassiliades, K, Wierman, ME, Altieri, B, Foster, PA & Ronchi, CL 2023, 'PLK1 inhibitors as a new targeted treatment for adrenocortical carcinoma', Endocrine Connections, vol. 13, no. 1, e230403. https://doi.org/10.1530/EC-23-0403

Eissa, AG, Powell, L, Gee, J, Foster, P & Simons, C 2023, 'Pyridine based dual binding site aromatase (CYP19A1) inhibitors', RSC Medicinal Chemistry. https://doi.org/10.1039/D2MD00352J

Dohle, W, Asiki, H, Gruchot, W, Foster, P, Sahota, H, Bai, R, Kirsten, C, Hamel, E & Potter, BVL 2022, '2-difluoromethoxy-substituted estratriene sulfamates: synthesis, antiproliferative SAR, antitubulin activity, and steroid sulfatase inhibition', ChemMedChem. https://doi.org/10.1002/cmdc.202200408

Eissa, AG, Barrow, D, Gee, J, Powell, L, Foster, P & Simons, C 2022, '4th Generation nonsteroidal aromatase inhibitors: An iterative SAR-guided design, synthesis, and biological evaluation towards picomolar dual binding inhibitors', European Journal of Medicinal Chemistry, vol. 240, 114569. https://doi.org/10.1016/j.ejmech.2022.114569

Barnard, L, Schiffer, L, Du-Toit, RL, Tamblyn, J, Chen, S, Africander, D, Arlt, W, Foster, P & Storbeck, K-H 2021, '11-oxygenated estrogens are a novel class of human estrogens but do not contribute to the circulating estrogen pool', Endocrinology, vol. 162, no. 3, bqaa231. https://doi.org/10.1210/endocr/bqaa231

Powell, L & Foster, P 2021, 'Protein disulphide isomerase inhibition as a potential cancer therapeutic strategy', Cancer Medicine, vol. 10, no. 8, pp. 2812-2825. https://doi.org/10.1002/cam4.3836

Mueller, JW, Vogg, N, Lightning, TA, Weigand, I, Ronchi, C, Foster, P & Kroiss, M 2021, 'Steroid sulfation in adrenal tumors', Journal of Clinical Endocrinology and Metabolism, vol. 2021, no. 00, dgab182, pp. 3385-3397. https://doi.org/10.1210/clinem/dgab182

El-gamal, MI, Zaraei, S, Foster, PA, Anbar, HS, El-gamal, R, El-awady, R & Potter, BVL 2020, 'A new series of aryl sulfamate derivatives: design, synthesis, and biological evaluation', Bioorganic & Medicinal Chemistry, vol. 28, no. 8, 115406. https://doi.org/10.1016/j.bmc.2020.115406

Grienke, U, Foster, P, Zwirchmayr, J, Tahir, A, Rollinger, JM & Mikros, E 2019, '1H NMR-MS-based heterocovariance as a drug discovery tool for fishing bioactive compounds out of a complex mixture of structural analogues.', Scientific Reports, vol. 9, 11113. https://doi.org/10.1038/s41598-019-47434-8

Grienke, U, Kaserer, T, Kirchweger, B, Lambrinidis, G, Kandel, RT, Foster, P, Schuster, D, Mikros, E & Rollinger, JM 2019, 'Steroid sulfatase inhibiting lanostane triterpenes – structure activity relationship and in silico insights', Bioorganic Chemistry, vol. 95, 103495. https://doi.org/10.1016/j.bioorg.2019.103495

Review article

Banibakhsh, A, Sidhu, D, Khan, S, Haime, H & Foster, PA 2023, 'Sex steroid metabolism and action in colon health and disease', The Journal of Steroid Biochemistry and Molecular Biology, vol. 233, 106371. https://doi.org/10.1016/j.jsbmb.2023.106371

Foster, P 2021, 'Steroid sulphatase and its inhibitors: past, present and future', Molecules, vol. 26, no. 10, 2852. https://doi.org/10.3390/molecules26102852

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