Role
Dr Amanda Miles is a Senior Research Fellow in the Biological Mass Spectrometry and Clinical Proteomics group in the John van Geest Cancer Research Centre. She is also involved in molecular cell biology and her main research interests focus on the identification of novel compounds for the treatment of cancer metastasis. In addition, she is responsible for the supervision of PhD, MSc and placement students and provides assistance and expertise in the delivery of cancer related subject areas and practical laboratory sessions.
Dr Amanda Miles is also responsible for managing the laser capture microdissection facility. This involves training new users in all aspects of laser capture microdissection, from sample staining techniques and optimisation, machine operation, image acquisition and downstream sample preparation, including the use of the software programs AxioVision and PalmRobo.
Career overview
Dr Miles graduated with a BSc (hons) in Biomedical Science at Nottingham Trent University (1996-2000), followed by a PhD (Molecular Cancer Biology) in the same department sponsored by the John and Lucille van Geest Foundation from 2000 to 2004. The PhD was entitled "The identification and characterisation of novel tumour antigens".
From 2004-2008 Dr Miles was project lead on a EU consortium grant (ALLOSTEM) that had the fundamental aim of identifying novel cell surface peptides that could be translated into therapeutic cancer targets. This involved the optimisation of tissue culture growth conditions, cell surface elution protocols and ESI-MSMS methods (Thermo LTQ).
From 2008-2012 Dr Miles then transferred her skills and became project lead for the identification of novel tumour antigens as immunotherapeutic targets. This role involved the in vitro screening of multiple cDNA expression libraries to identify potential immunogenic tumour antigens. Robust transcriptomic analysis of the antigens and subsequent protein expression analysis using IHC.
In 2012 Dr Miles became Senior Research Fellow and project lead for the development of novel beta blockers as adjuvant therapies for breast cancer. This role involves the design and timely execution of in vitro methodologies to investigate the potential role of these compounds in preventing breast cancer metastasis. The project involves cross disciplinary collaborations with the Department of Chemistry at NTU and Nottingham University Hospitals NHS Trust.
Research areas
Current Research Areas:
1. The design of novel beta blockers for the retardation of breast cancer metastasis: Epidemiological studies have shown a significant association between β-blocker usage and improved breast cancer patient outcome. These studies found that patients with triple negative breast cancer (TNBC) benefited the most from simultaneous intake of β-blockers. The rationale for using novel β2-selective β-blockers as a therapy for basal TNBC derives from their capacity to inhibit catecholamine-induced activation of G protein-coupled β2-adrenoceptors that drive cancer cell signalling pathways and cancer cell migration. Additional data obtained from pre-clinical and epidemiological studies has led to the hypothesis that β2-selective blockers are key mediators in preventing BC progression, rather than the β1-selective or β1/β2 non-selective counterparts. A panel of novel small molecules have recently been developed between Dr Amanda Miles (Jon van Geest Centre, NTU) and the synthetic chemistry laboratory of Prof John Wallis and Dr Chris Garner (Department of Chemistry and Forensics, NTU). Current work demonstrates that one of these novel compounds is able to significantly reduce the migration and invasion of breast cancer cells in vitro. We would now like to: (i) further investigate the novel compound’s biological effects and pharmacological profile (in collaboration with Dr Carl Nelson); (ii) investigate the metabolism and pharmacokinetic dynamics of the novel compound; before (iii) identifying its clinical utility in vivo. Furthermore, the synthetic chemistry component of the project is ongoing and concerns the preparation and purification of more of the most biologically active materials, as well as extending the family of drug candidates by making small molecular changes to the molecular structure of the lead. This interdisciplinary approach encompasses the range of skills needed in modern day drug development including computer aided drug design, chemical synthesis, receptor binding studies and subsequent biological testing of the compounds.
2. Combined novel beta-blocker and chemotherapy as a targeted treatment for breast cancer: Studies performed in our laboratory have shown that the novel beta blocker does not inhibit cell proliferation at therapeutically relevant concentrations. Modern day chemotherapeutics work on rapidly dividing cells and recent studies have shown that beta blockers can enhance the anti-proliferative effects of certain chemotherapeutic agents. In addition, administering a beta blocker also reduces the cardiotoxic effects that the chemotherapies have on the heart. Current research in our lab involves investigating the concomitant administration of our novel beta blocker with a anti-proliferative chemotherapeutic to investigate its effects on cancer proliferation, angiogenesis and metastasis.
3. Biological mass spectrometry as a tool for biomarker discovery: Within the mass spectrometry group Dr Miles is developing in vitro methods to define the impact of drug treatment on cancer cells at both the proteomic and secretomic levels. This is primarily in breast and prostate cancer but this work has also been extended to include bacterial samples.
“Opportunities arise to carry out postgraduate research towards an MPhil / PhD in all of the areas identified above. Further information may be obtained on the NTU Research Degrees website https://www.ntu.ac.uk/research/research-degrees-at-ntu
External activity
Dr Miles is a member of the British Mass Spectrometry Society (BMSS) and is part of the organising committee of the East Midlands Proteomics Workshop.
Dr Miles peer reviews original papers for research journals and also reviews grant applications for several funding bodies.
Sponsors and collaborators
Dr Miles has current collaborations with scientists working at the Universities of Nottingham, Newcastle and Ludwig-Maximilians-Universität München (LMU Munich), along with other internal collaborators including Dr Tarik Regad, Dr Amanda Coutts and Professor John Wallis. She also collaborates with clinicians at Nottingham City Hospital.
Dr Miles is actively seeking research funding and has several grant applications under review.
Publications
Selected publications:
The localization of pre mRNA splicing factor PRPF38B is a novel prognostic biomarker that may predict survival benefit of trastuzumab in patients with breast cancer overexpressing HER2. Tarek M.A. Abdel-Fatah, Robert C. Rees, A. Graham Pockley, Paul Moseley, Graham R. Ball, Stephen Y.T. Chan, Ian O. Ellis and Amanda K. Miles. Oncotarget. 8:112245-112257. (2017)
The origins of the Selden map of China: scientific analysis of the painting materials and techniques using a holistic approach. Sotiria Kogou, Sarah Neate, Clare Coveney, Amanda Miles, David Boocock, Lucia Burgio, Chi Shing Cheung and Haida Liang. Heritage Science. 4:28. (2016)
Cytoplasmic PML promotes TGF-β-associated epithelial-mesenchymal transition and invasion in prostate cancer. Buczek ME, Miles AK, Green W, Johnson C, Boocock DJ, Pockley AG, Rees RC, Hulman G, van Schalkwky G, Parkinson R, Hulman J, Regad T. Oncogene. Jun 30;35(26):3465–75. (2015)
The helicase HAGE prevents interferon-a-induced PML expression in ABCB5+ malignant melanoma-initiating cells by promoting the expression of SOCS1. Mathieu MG, Miles AK, Ahmad M, Buczek ME, Pockley AG, Rees RC and Regad T. Cell Death and Disease. 5(2). (2014)
Identification of novel breast cancer-associated transcripts by uniGene database mining and gene expression analysis in normal and malignant cells. Laversin SA, Phatak VM, Powe DG, Li G, Miles AK, Hughes DC, Ball GR, Ellis IO, Gritzapis AD, Missitzis I, McArdle SE, Rees RC. Genes Chromosomes Cancer. Dec 8. (2012)
The helicase HAGE expressed by malignant melanoma-initiating cells is required for tumor cell proliferation in vivo. Linley AJ, Mathieu MG, Miles AK, Rees RC, McArdle SEB, Regad T, Journal of Biological Chemistry. 287 (17), 13633-13643. (2012)
Identification of SPARC-like 1 protein as part of a biomarker panel for Alzheimer's disease in cerebrospinal fluid. Vafadar-Isfahani B, Ball G, Coveney C, Lemetre C, Boocock D, Minthon L, Hansson O, Miles AK, Janciauskiene SM, Warden D, Smith AD, Wilcock G, Kalsheker N, Rees R, Matharoo-Ball B, Morgan K. J Alzheimers Dis. 28(3):625-36. (2012)
Expression of the tumour antigen T21 is up-regulated in prostate cancer and is associated with tumour stage. Miles AK, Rogers A, McCulloch T, Hodi Z, McArdle S, Bishop M, Rees RC. BJU Int. Mar;109(5):796-805. (2012)
Serum biomarkers which correlate with failure to respond to immunotherapy and tumor progression in a murine colorectal cancer model. Vafadar-Isfahani B, Laversin SAS, Ahmad M, Ball G, Coveney C, Lemetre C, Miles AK, van Schalkwyk G, Rees R, Matharoo-Ball B. PROTEOMICS-Clinical Applications. 4: 682-696. (2010)
Identification of a novel prostate cancer-associated tumor antigen. Miles AK, Rogers A, Li G, Seth R, Powe D, McArdle SE, McCulloch TA, Bishop MC, Rees RC. Prostate. Feb 15:67(3):274-87. (2007)
Diagnostic biomarkers differentiating metastatic melanoma patients from healthy controls identified by an integrated MALDI-TOF mass spectrometry/bioinformatic approach. Matharoo-Ball B, Ratcliffe L, Lancashire L, Ugurel S, Miles AK, Weston DJ, Rees R, Schadendorf D, Ball G, Creaser C. Proteomics Clin Applic. 1:605-620. (2007)
For a full list of publications please link to Dr Miles ORCID
Press expertise
Proteomics and mass spectrometry
Laser capture microdisection
Prostate and breast cancer
Small molecule inhibitors of metastatic disease