Dr James Hislop

Dr James Hislop
Dr James Hislop
Dr James Hislop

BSc Hons, PhD

Lecturer

About
Email Address
james.hislop@abdn.ac.uk
Telephone Number
+44 (0)1224 437399
Office Address

6.19 Institute of Medical Sciences

School/Department
School of Medicine, Medical Sciences and Nutrition

Biography

I received my B.Sc in Pharmacology from the University of Bristol in 1997, before going on to undertake a Ph.D in the department of Medicine, also at the University of Bristol, under the supervision of Prof Craig McArdle, where I investigated the role of endocytosis in the function of the Gonadotropin Releasing Hormone Receptor.  On completion of my PhD, I took a postdoctoral position at the University of California, San Francisco, where I continued my training in the laboratory of Prof Mark von Zastrow, a renowned leader in the field of endocytic trafficking in the function of G-protein-coupled receptors, where I investigated the role of Ubiquitin in endosomal trafficking.  In 2011, I returned to the UK to work in the Gene Therapy Group at Imperial College London, in the laboratory of Prof Nicholas Mazarakis, where I studied how lentiviral vectors undergo trafficking within motor neurones.  I was appointed Lecturer in Pharmacology at the University of Aberdeen in January 2013

Qualifications

  • BSc Pharmacology 
    1997 - University of Bristol 
  • PhD Pharmacology/Endocrinology 
    2001 - University of Bristol 

External Memberships

British Pharmacological Society

Research

Research Overview

My research involves investigating the mechanisms by which G-protein-coupled Receptors are regulated to maintain signalling and homeostasis. G-protein coupled receptors (GPCRs), represent the largest family of cell surface receptors and are the prime regulators of many physiological systems.  Their undoubted importance is demonstrated by the fact that as many as 50% of marketed drugs target GPCRs. Although there are >300 distinct GPCRs there are a number of similarities between how these different types are regulated, but also a number of differences, and it is these differences that have the most potential for therapeutic intervention.

The ability of a cell to respond to extracellular signals such as neurotransmitters is vital for regulating normal physiological function.  One important aspect of this regulation is determining how many receptors are available to respond at any one time. Too few receptors and the signal is missed, too many and the signal overwhelms the cell.  This process of desensitisation and resensitisation is important for the cell, and underlies, in part, the phenomenon of pharmaceutical tolerance.  This signalling fidelity of GPCRs is maintained by an elegant series of interactions that firstly prevent signalling and is followed by a regulated trafficking process involving the removal of desensitised receptors from the surface of the cell (internalisation) followed by either recycling to the plasma membrane for repeated signalling (resensitisation) or targeting to the lysosome for destruction and downregulation (Figure 1).  Although a great deal of progress has been made in understanding the processes underlying receptor endocytosis, including the critical role of receptor kinases and arrestin, comparatively little is known about the processes determining the postendocytic fate of GPCRs.  My specific interests lie in how the levels of receptor are maintained or downregulated in the extended presence of agonist, and what mechanisms determine how receptors are sorted to the lysosome, in particular determining the distinct processes that control different receptor types.

Figure 1 - Simplified model of GPCR post-endocytic sorting.   Following endocytosis GPCRs can undergo recycling to the plasma membrane (1) (possibly regulated by the retromer) or sorting to the lysosome.  This can involve ubiquitin regulated sorting by the ESCRT complex (2), initial ubiquitin-indendent sorting (possibly by GASP) before ubiquitin and ESCRT mediated transfer to Intralumenal vesicles (3) or direct interaction with the ESCRT III component, independent of ubiquitination (4) mediated by ALIX.

One area of particular interest is the role of ubiquitination in directing receptor translocation to intralumenal vesicles and its requirement or otherwise for trafficking to the lysosome. For many proteins ubiquitin is critical for controlling the degradation of receptors, but it is unknown what proteins are responsible for controlling this (e.g. the nature of the ubiquitin ligase) The images show a clear requirement for receptor (green) to be ubiquitinated or it remains on the endosome limiting membrane.  However it is still able to undergo limited proteolysis with N-terminal fragments (red) being seen within the lumen of the endosome in some cases.  This fragementation can be further visualised by Western blot (Henry et al, 2011).

 

Research Areas

Biomedical Sciences

Research Specialisms

  • Pharmacology
  • Neuroscience
  • Cell Biology

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 Projects

  • Investigating the link between endocytic trafficking and signalling
  • The role of endocytic trafficking of FPR2 in the regulation of the inflammatory response (In collaboration with Dr D Thompson)
  • The role of ubiquitination in the regulation of muscarinic acetylcholine receptors
  • The role of downregulation of beta adrenergic receptors in cellular signalling
  • Cannabinoid Receptor expression and function in the development of colorectal and prostate cancer (Funded by Friends of Anchor and NHS Grampian)
  • Signalling Bias and trafficking and the development of novel compounds at cannabinoid receptors (In collaboration with Prof M Decker)

Post-Graduate Positions available

I am taking applications for self funded Masters students for any of the research areas above. Please contact me if you are interested.

Masters' Programme | The School of Medicine, Medical Sciences and Nutrition | The University of Aberdeen (abdn.ac.uk)

Funding and Grants

Current and Previous Funders:

  • BBSRC - EastBio-DTP
  • Friends of Anchor
  • NHS Grampian
  • Tenovus Scotland
Teaching

Teaching Responsibilities

I currently teach on and am the course coordinator of the Honours year undergraduates module Molecular Pharmacology (PA4005). I also lecture on the BM3501 - Cardiovascular Physiology and Pharmacology, and BM3502 - Neuroscience and Neuropharmacology and Molecular Pharmacology on the Clinical Pharmacology MSc course (MT5024).  I supervise undergraduate and MSc students for lab based research projects

Publications

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  • Visible-Light Photoswitchable Benzimidazole Azo-Arenes as beta-Arrestin2-Biased Selective Cannabinoid 2 Receptor Agonists

    Steinmueller, S. A. M., Fender, J., Deventer, M. H., Tutov, A., Lorenz, K., Stove, C. P., Hislop, J., Decker, M.
    Angewandte Chemie International Edition, vol. 62, no. 49, e202306176
    Contributions to Journals: Articles
  • Bridging the Binding Sites 2.0: Photoswitchable Dualsteric Ligands for the Cannabinoid 2 Receptor

    Steinmüller, S. A. M., Tutov, A., Hislop, J. N., Decker, M.
    ACS Chemical Neuroscience, vol. 14, no. 20, pp. 3737-3744
    Contributions to Journals: Letters
  • Bridging the Binding Sites: Dualsteric Ligands for the Cannabinoid 2 Receptor (CB2R)

    Tutov, A., Steinmüller, S. A. M., Ramírez, Y. A., Jack, C. E., Rodríguez-Soacha, D. A., Sotriffer, C., Hislop, J. N., Decker, M.
    Advanced Therapeutics, vol. 6, no. 4, 2200260
    Contributions to Journals: Articles
  • Using Game of Thrones to teach physiology during lockdown and beyond.

    Scott, D. A., Hislop, J., Murray, F., Thompson, D.
    Contributions to Conferences: Oral Presentations
  • Development of an Indole-Amide-Based Photoswitchable Cannabinoid Receptor Subtype 1 (CB1R) "Cis-On" Agonist.

    Rodríguez-Soacha, D. A., Steinmüller, S. A. M., Işbilir, A., Fender, J., Deventer, M. H., Ramírez, Y. A., Tutov, A., Sotriffer, C., Stove, C. P., Lorenz, K., Lohse, M. J., Hislop, J. N., Decker, M.
    ACS Chemical Neuroscience, vol. 13, no. 16, pp. 2410–2435
    Contributions to Journals: Articles
  • Using Game of Thrones to teach neuroscience and neuropharmacology during lockdown

    Scott, D. A., Hislop, J., Murray, F., Thompson, D.
    University of Aberdeen Annual Academic Development Symposium 2021
    Contributions to Conferences: Posters
  • New Insights into Phosphodiesterase 1C as a Novel Target for Pulmonary Arterial Hypertension

    Al Bakour, Z., Hislop, J., Breitenbucher, J., Murray, F.
    2000 Meeting of the British-Pharmacological-Society (PHARMACOLOGY), pp. 424-425
    Contributions to Journals: Abstracts
  • Endocytic Sorting and Downregulation of the M2 Acetylcholine Receptor is Regulated by Ubiquitin and the ESCRT Complex

    Zenko, D., Thompson, D., Hislop, J. N.
    Neuropharmacology, vol. 162, 107828
    Contributions to Journals: Articles
  • A synthetic analogue of cannabidiolic acid that acts like a positive allosteric modulator at 5-HT1A receptors

    Alcina, A. G., Stevenson, L. A., Haj, C., Smoum, R., Mechoulam, R., Hislop, J. N., Pertwee, R. G.
    British-Pharmacology-Society Meeting (Pharmacology), pp. 3011-3012
    Contributions to Journals: Abstracts
  • Student-created video resources can enhance medical science practical class assessment

    Malcolm, C. J., Kirkman, J., Jenkinson, A. M., Hislop, J. N., Murray, F., Scott, D. A.
    Contributions to Conferences: Papers
  • Student perceptions of Objective Structured Practical Examination (OSPE) assessments

    Malcolm, C. J., Kirkman, J., Jenkinson, A., Hislop, J. N., Murray, F., Scott, D. A.
    Pharmacology 2018
    Contributions to Conferences: Posters
  • Two Years On: How the Core Curriculum has Shaped Pharmacology Courses at the University of Aberdeen

    Tucker, S., Fleming, I. N., Hislop, J. N., Murray, F., Scott, D. A., Wallace, H. M.
    Contributions to Specialist Publications: Featured Articles
  • Regulation and trafficking of muscarinic acetylcholine receptors

    Zenko, D., Hislop, J. N.
    Neuropharmacology, vol. 136, no. Part C, pp. 374-382
    Contributions to Journals: Review articles
  • Adapting Objective Structured Practical Examinations (OSPE’s) to assess laboratory science skills in pharmacology students

    Scott, D. A., Hislop, J. N., Jenkinson, A.
    HEA STEM Annual Conference
    Contributions to Conferences: Posters
  • Identification of a novel recycling sequence in the C-tail of FPR2/ALX: association with cell protection from apoptosis

    Thompson, D., McArthur, S., Hislop, J. N., Flower, R. J., Perretti, M.
    The Journal of Biological Chemistry, vol. 289, pp. 36166-36178
    Contributions to Journals: Articles
  • Rabies virus envelope glycoprotein targets lentiviral vectors to the axonal retrograde pathway in motor neurons

    Hislop, J. N., Islam, T. A., Eleftheriadou, I., Carpentier, D. C. J., Trabalza, A., Parkinson, M., Schiavo, G., Mazarakis, N. D.
    The Journal of Biological Chemistry, vol. 289, no. 23, pp. 16148-16163
    Contributions to Journals: Articles
  • Venezuelan equine encephalitis virus glycoprotein pseudotyping confers neurotropism to lentiviral vectors

    Trabalza, A., Georgiadis, C., Eleftheriadou, I., Hislop, J. N., Ellison, S. M., Karavassilis, M. E., Mazarakis, N. D.
    Gene Therapy, vol. 20, no. 7, pp. 723-732
    Contributions to Journals: Articles
  • Regulation of endocytic clathrin dynamics by cargo ubiquitination

    Henry, A. G., Hislop, J. N., Grove, J., Thorn, K., Marsh, M., von Zastrow, M.
    Developmental Cell, vol. 23, no. 3, pp. 519-532
    Contributions to Journals: Articles
  • Ubiquitination in the first cytoplasmic loop of μ-opioid receptors reveals a hierarchical mechanism of lysosomal down-regulation

    Hislop, J. N., Henry, A. G., von Zastrow, M.
    The Journal of Biological Chemistry, vol. 286, no. 46, pp. 40193-40204
    Contributions to Journals: Articles
  • Role of ubiquitination in endocytic trafficking of G-protein-coupled receptors

    Hislop, J. N., von Zastrow, M.
    Traffic, vol. 12, no. 2, pp. 137-148
    Contributions to Journals: Articles
  • The role of ubiquitination in lysosomal trafficking of δ-opioid receptors

    Henry, A. G., White, I. J., Marsh, M., von Zastrow, M., Hislop, J. N.
    Traffic, vol. 12, no. 2, pp. 170-184
    Contributions to Journals: Articles
  • Analysis of GPCR localization and trafficking

    Hislop, J. N., von Zastrow, M.
    Receptor Signal Transduction Protocols: Third Edition. Willars, G. B., Challiss, R. A. J. (eds.). Humana Press, pp. 425-440, 16 pages
    Chapters in Books, Reports and Conference Proceedings: Chapters
  • Ubiquitination regulates proteolytic processing of G protein-coupled receptors after their sorting to lysosomes

    Hislop, J. N., Henry, A. G., Marchese, A., von Zastrow, M.
    The Journal of Biological Chemistry, vol. 284, no. 29, pp. 19361-19370
    Contributions to Journals: Articles
  • Alternative splicing determines the post-endocytic sorting fate of G-protein-coupled receptors

    Tanowitz, M., Hislop, J. N., von Zastrow, M.
    The Journal of Biological Chemistry, vol. 283, no. 51, pp. 35614-35621
    Contributions to Journals: Articles
  • Internalization of gonadotropin-releasing hormone receptors (GnRHRs): does arrestin binding to the C-terminal tail target GnRHRs for dynamin-dependent internalization?

    Hislop, J. N., Caunt, C. J., Sedgley, K. R., Kelly, E., Mundell, S., Green, L. D., McArdle, C. A.
    Journal of Molecular Endocrinology, vol. 35, no. 1, pp. 177-89
    Contributions to Journals: Articles
  • Regulation of gonadotropin-releasing hormone receptors by protein kinase C: inside out signalling and evidence for multiple active conformations

    Caunt, C. J., Hislop, J. N., Kelly, E., Matharu, A., Green, L. D., Sedgley, K. R., Finch, A. R., McArdle, C. A.
    Endocrinology, vol. 145, no. 8, pp. 3594-602
    Contributions to Journals: Articles
  • Role of mammalian vacuolar protein-sorting proteins in endocytic trafficking of a non-ubiquitinated G protein-coupled receptor to lysosomes

    Hislop, J. N., Marley, A., Von Zastrow, M.
    The Journal of Biological Chemistry, vol. 279, no. 21, pp. 22522-31
    Contributions to Journals: Articles
  • Signaling and antiproliferative effects of type I and II gonadotropin-releasing hormone receptors in breast cancer cells

    Finch, A. R., Green, L., Hislop, J. N., Kelly, E., McArdle, C. A.
    Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 4, pp. 1823-32
    Contributions to Journals: Articles
  • Signalling and anti-proliferative effects mediated by gonadotrophin-releasing hormone receptors after expression in prostate cancer cells using recombinant adenovirus

    Franklin, J., Hislop, J. N., Flynn, A., McArdle, C. A.
    Journal of Endocrinology, vol. 176, no. 2, pp. 275-84
    Contributions to Journals: Articles
  • Signalling, cycling and desensitisation of gonadotrophin-releasing hormone receptors

    McArdle, C. A., Franklin, J., Green, L., Hislop, J. N.
    Journal of Endocrinology, vol. 173, no. 1, pp. 1-11
    Contributions to Journals: Articles
  • The gonadotrophin-releasing hormone receptor: signalling, cycling and desensitisation

    McArdle, C. A., Franklin, J., Green, L., Hislop, J. N.
    Archives of Physiology and Biochemistry, vol. 110, no. 1-2, pp. 113-122
    Contributions to Journals: Articles
  • Signaling and antiproliferative effects mediated by GnRH receptors after expression in breast cancer cells using recombinant adenovirus

    Everest, H. M., Hislop, J. N., Harding, T., Uney, J. B., Flynn, A., Millar, R. P., McArdle, C. A.
    Endocrinology, vol. 142, no. 11, pp. 4663-72
    Contributions to Journals: Articles
  • Differential internalization of mammalian and non-mammalian gonadotropin-releasing hormone receptors. Uncoupling of dynamin-dependent internalization from mitogen-activated protein kinase signaling

    Hislop, J. N., Everest, H. M., Flynn, A., Harding, T., Uney, J. B., Troskie, B. E., Millar, R. P., McArdle, C. A.
    The Journal of Biological Chemistry, vol. 276, no. 43, pp. 39685-94
    Contributions to Journals: Articles
  • Desensitization and internalization of human and xenopus gonadotropin-releasing hormone receptors expressed in alphaT4 pituitary cells using recombinant adenovirus

    Hislop, J. N., Madziva, M. T., Everest, H. M., Harding, T., Uney, J. B., Willars, G. B., Millar, R. P., Troskie, B. E., Davidson, J. S., McArdle, C. A.
    Endocrinology, vol. 141, no. 12, pp. 4564-75
    Contributions to Journals: Articles
  • The lack of gonadotrophin-releasing hormone (GnRH) receptor desensitisation in alphaT3-1 cells is not due to GnRH receptor reserve or phosphatidylinositol 4,5-bis-phosphate pool size

    Forrest-Owen, W., Willars, G. B., Nahorski, S. R., Assefa, D., Davidson, J. S., Hislop, J., McArdle, C. A.
    Molecular and Cellular Endocrinology, vol. 147, no. 1-2, pp. 161-173
    Contributions to Journals: Articles

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