![Professor Iain McEwan Professor Iain McEwan](/img/200x200/staffpages/uploads/bch167/avatar/TqFYuqQOtpbnVst0jHNDFekyVDmdMKV2iLYK7Z1x.jpeg)
BSc (Hons), PhD
Personal Chair, Interim Director of Institute of Medical Sciences
- About
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- Email Address
- iain.mcewan@abdn.ac.uk
- Telephone Number
- +44 (0)1224 437328
- Office Address
- School/Department
- School of Medicine, Medical Sciences and Nutrition
Biography
Iain McEwan graduated with a first in Biochemistry from the University of Strathclyde in 1983, and went on to gain a PhD in 1987 from the University of Glasgow.
From 1986-1989 he worked as a Postdoctoral research fellow at the Friedrich Meischer Institute in Basel, Switzerland. He then moved to Sweden where he gained experience working as a Postdoctoral research fellow at the Karolinska Institute, Stockholm and then as a Junior group leader in the Department of Biosciences at Novum, Karolinska Institute, Stockholm, Sweden.
In 1997 he moved south (!) to take up a lectureship at the University of Aberdeen and in 2003 was made a Senior Lecturer, Reader in 2005 and awarded a Personal Chair in 2009.
- Research
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Research Overview
The research of my group focuses on investigating the molecular mechanisms of action of the human androgen receptor and translating fundametal descoveries to the clinic. The androgen receptor is an intracellular receptor protein that acts as the 'gatekeeper' for the actions of the male steroid hormones testosterone and dehydrotestosterone. The androgen receptor functions as a liganded-activated transcription factor that both up-and down-regulates networks of genes in target tissues. Mutations in the receptor can lead to a disruption of male development (androgen insensitivity) and a neuromuscular degenerative disorder (Kennedy's disease). Mutations have also been identified in patients with prostate cancer both before and after hormone therapy. It has been proposed that such mutations may influence the effectiveness of androgen ablation therapy and play a role in the progression to hormone-refractory disease.
The androgen receptor is organised into discrete structural and functional domains, consisting of a central DNA binding domain (DBD), flanked by a C-terminal ligand binding domain (LBD), and a structurally distinct N-terminal domain (NTD) important for receptor-dependent transactivation. The androgen receptor can regulate both the initiation and elongation steps of the transcription cycle and we have identified and characterised an interaction between the receptor and the general transcription factor TFIIF, which appears important for the transcription initiation steps (see model). We have also shown that the androgen receptor-transactivation domain folds into a more stable conformation, possibly involving alpha-helix formation, resistant to protease attack, in the presence of the target protein TFIIF or the structure stabilising solutes trimethylene N-oxide (TMAO) and trifluorethanol (TFE). Thus our working hypothesis is that the receptor-NTD is structurally flexible, permitting multiple protein-protein interactions with the transcriptional machinery. Specific protein-protein interactions will induce folding of the receptor-transactivation domain and provide a platform for the assembly of a transcriptionally competent complex, containing basal transcription factors and co-activator proteins (SRC, CBP).
Recently, we have extended these studies to investigate the structure-function of the human mineralocorticoid receptor N-terminal domain. The mineralocorticoid receptor is a risk factor in hypertension, cardiovascular disease and metabolic synodrome. This region has a complex transactivation function consisting of different sub-domains which exhibit different functional and/or structural properties. Current work aims to investigate the translational potential of these studies in the treatment of hormone-dependent diseases.
Several potential PhD project opportunities are available:
- Therapeutic Targeting of the Structurally Plastic N-terminal Domain of Steroid Receptors
- Tissue-selective regulation and expression of the human androgen receptor gene
Research Areas
Accepting PhDs
I am currently accepting PhDs in Biomedical Sciences.
Please get in touch if you would like to discuss your research ideas further.
Research Specialisms
- Biochemistry
- Molecular Biology
- Biomolecular Science
- Endocrinology
Our research specialisms are based on the Higher Education Classification of Subjects (HECoS) which is HESA open data, published under the Creative Commons Attribution 4.0 International licence.
Current Research
Current research focuses on two main themes:
1. The expression and control of the androgen receptor gene in male and female tissues, including prostate, bladder and bone. We are also investigating the role of steroid hormones action on immune cell function in health and cancer. These projects are in collaboration with Professor Heather Wilson (IMS https://www.abdn.ac.uk/ims/research/profiles/h.m.wilson) and Professor Philippa Saunders and Dr Douglas Gibson University of Edinburgh.
2. Developing novel therapeutic strategies to switch off androgen receptor function in cancer cells. These projects involve medicinal chemistry approaches to synthesising bespoke small molecule inhibitors and novel biologics called SoloMERs in collaboration with the biopharmaceutical company Elasmogen (https://www.elasmogen.com/about-elasmogen/).
Collaborations
My group collaborates with a number of colleagues in both nationally (UK) and internationally (The Netherlands, Spain and North America). Current interdisplenary collaborative projects focus on mathematical modelling of gene expression and medicinal chemistry. We also have a collaboration with a local biopharmacetical company, called Elasmogen invetigating biologics as novel therapeutics in hormone-dependent cancers.
Supervision
My current supervision areas are: Biomedical Sciences.
I have successfully supervised more than 10 PhD students since joining the UNiversity of Aberdeen. I am currently supervising four students: two in their first year; one second year; and one in the final year.
Funding and Grants
Research in my laboratory is currently supported by:
Projects grants from the Prostate Cancer Research Centre (https://www.prostate-cancer-research.org.uk/), the Medical Research Council (DPFS award) (https://mrc.ukri.org/) and Pilot STudy Award from Friends of Anchor (https://www.friendsofanchor.org/).
PhD studentship awards from Cranes (https://www.cranes.org.uk/), EASTBIO-BBSRC (http://www.eastscotbiodtp.ac.uk/) and Aberdeen Cancer PhD programme (https://www.abdn.ac.uk/smmsn/research/biobank-1025.php).
- Teaching
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Courses
Teaching Responsibilities
I am course coordinator for Honours Biochemistry Option 1 (BC4014).
Non-course Teaching Responsibilities
Personal Tutor
- Publications
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Page 2 of 2 Results 51 to 80 of 80
Like clock work: pulses of gene regulation by natural glucocorticoid steroid hormones
cell science reviews, vol. 6, no. 2Contributions to Journals: Literature ReviewsNuclear Receptors: One Big Family
The Nuclear Receptor Superfamily: Methods and Protocols. Humana Press, pp. 3-18, 16 pagesChapters in Books, Reports and Conference Proceedings: Chapters- [ONLINE] DOI: https://doi.org/10.1007/978-1-60327-575-0_1
Using intrinsic fluorescence emission spectroscopy to study steroid receptor and coactivator protein conformation dynamics
The Nuclear Receptor Superfamily: Methods and Protocols. McEwan, I. J. (ed.). Humana Press, pp. 205-218, 14 pagesChapters in Books, Reports and Conference Proceedings: Chapters- [ONLINE] DOI: https://doi.org/10.1007/978-1-60327-575-0_12
Consequences of poly-glutamine repeat length for the conformation and folding of the androgen receptor amino-terminal domain
Journal of Molecular Endocrinology, vol. 41, no. 5, pp. 301-314Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1677/JME-08-0042
Functional Characterisation of the Native NH2- Terminal Transactivation Domain of the Human Androgen Receptor: Binding Kinetics for Interactions with TFIIF and SRC-1a
Biochemistry, vol. 47, no. 11, pp. 3352-3359Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1021/bi702220p
Structural characterization of the native NH2-terminal transactivation domain of the human androgen receptor: a collapsed disordered conformation underlies structural plasticity and protein-induced folding
Biochemistry, vol. 47, no. 11, pp. 3360-3369Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1021/bi702221e
The Nuclear Receptor Superfamily Methods and Protocols
Methods in Molecular Biology, vol. 550Contributions to Journals: Reviews of Books, Films and ArticlesThe human androgen receptor AF1 transactivation domain: interactions with transcription factor IIF and molten-globule-like structural characteristics
Biochemical Society Transactions, vol. 34, pp. 1054-1057Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1042/BST0341054
Structural dynamics of the human androgen receptor: implications for prostate cancer and neurodegenerative disease
Biochemical Society Transactions, vol. 34, pp. 1098-1102Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1042/BST0341098
Induced alpha-Helix Structure in the Aryl Hydrocarbon Receptor Transactivation Domain Modulates Protein-Protein Interactions
Biochemistry, vol. 44, pp. 734-743Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1021/bi0487701
Intra-domain Communication Between the N-Terminal and DNA-binding Domains of the Androgen Receptor: Modulation of Androgen Response Element DNA Binding.
Journal of Molecular Endocrinology, vol. 34, pp. 603-615Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1677/jme.1.01723
Mutation of Histidine 874 in the Androgen Receptor Ligand Binding Domain Leads to Promiscuous Ligand Activation and Altered p160 Coactivator Interactions
Molecular Endocrinology, vol. 19, pp. 2943-2954Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1210/me.2005-0231
Structure and Function of Steroid Receptor AF1 Transactivation Domains: Induction of Active Conformations
Biochemical Journal, vol. 389, pp. 449-464Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1042/BJ20050872
In Vitro regulation of reporter gene transcription by the androgen receptor AF1 domain
Biochemical Society Transactions, vol. 32, pp. 1103-1106Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1042/BST0321103
Induced alpha-helix Structure in AF1 of the Androgen Receptor Upon Binding Transcription Fcator TFIIF
Biochemistry, vol. 43, no. 11, pp. 3008-3013Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1021/bi035934p
Molecular mechanisms of androgen receptor-mediated gene regulation: structure-function analysis of the AF-1 domain
ENDOCRINE-RELATED CANCER, vol. 11, no. 2, pp. 281-293Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1677/erc.0.0110281
Sex, drugs and gene expression: signalling by members of the nuclear receptor superfamily
Essays in BiochemistryContributions to Journals: Review articles- [ONLINE] DOI: https://doi.org/10.1042/bse0400001
The nuclear receptor superfamily: Preface
Essays in Biochemistry, vol. 40, pp. xi-xiiContributions to Journals: Editorials- [ONLINE] View publication in Scopus
Role of conserved hydrophobic amino acids in androgen receptor AF-1 function
Journal of Molecular Endocrinology, vol. 31, no. 3, pp. 427-439Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1677/jme.0.0310427
The androgen receptor transactivation domain: the interplay between protein conformation and protein-protein interactions
Biochemical Society Transactions, vol. 31, no. Pt 5, pp. 1042-1046Contributions to Journals: ArticlesThe androgen receptor interacts with multiple regions of the large subunit of general transcription factor TFIIF
The Journal of Biological Chemistry, vol. 277, no. 43, pp. 41247-41253Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1074/jbc.M205220200
Conformational analysis of the androgen receptor amino-terminal domain involved in transactivation. Influence of structure-stabilizing solutes and protein-protein interactions
The Journal of Biological Chemistry, vol. 277, no. 22, pp. 20079-20086Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1074/jbc.M201003200
Bakers yeast rises to the challenge: reconstitution of mammalian steroid receptor signalling in S. cerevisiae
Trends in Genetics, vol. 17, no. 5, pp. 239-243Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1016/S0168-9525(01)02273-9
Structural and functional alterations in the androgen receptor in spinal bulbar muscular atrophy
Biochemical Society Transactions, vol. 29, no. Pt 2, pp. 222-227Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1042/BST0290222
Gene regulation through chromatin remodelling by members of the nuclear receptor superfamily
Biochemical Society Transactions, vol. 28, pp. 369-373Contributions to Journals: ArticlesThe nuclear-receptor interacting protein (RIP) 140 binds to the human glucocorticoid receptor and modulates hormone-dependent transactivation
The Journal of Steroid Biochemistry and Molecular Biology, vol. 71, no. 3-4, pp. 93-102Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1016/S0960-0760(99)00128-4
Erratum: Investigation of steroid receptor function in the budding yeast Saccharomyces cerevisiae (FEMS Microbiology Letters 176 (1999) (1-9) PII: 037810999001767)
FEMS Microbiology Letters, vol. 179, no. 1, pp. 183-184Contributions to Journals: Comments and Debates- [ONLINE] DOI: https://doi.org/10.1016/S0378-1097(99)00395-X
- [ONLINE] View publication in Scopus
Investigation of steroid receptor function in the budding yeast Saccharomyces cerevisiae
FEMS Microbiology Letters, vol. 176, pp. 1-9Contributions to Journals: Literature Reviews- [ONLINE] FEMS Microbiology Letters
Interaction of the human androgen receptor transactivation function with the general transcription factor TFIIF
Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 16, pp. 8485-8490Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1073/pnas.94.16.8485
- [ONLINE] View publication in Scopus
Mechanism of gene expression by the glucocorticoid receptor: Role of protein-protein interactions
BioEssays, vol. 19, no. 2, pp. 153-160Contributions to Journals: Review articles- [ONLINE] DOI: https://doi.org/10.1002/bies.950190210
- [ONLINE] View publication in Scopus