Dr Sophie Bradley

  • Honorary Senior Research Fellow (School of Molecular Biosciences)

email: Sophie.Bradley@glasgow.ac.uk

Sosei Heptares, Steinmetz Building, Granta Park, Great Abington, CB21 6DG

Import to contacts

ORCID iDhttps://orcid.org/0000-0002-0035-4090

Biography

Current Position

2020-present: Senior lecturer, Molecular Pharmacology, Institute of Molecular, Cell and Systems Biology, University of Glasgow
My research is focussed on defining the physiological roles of G protein-coupled receptors (GPCRs) and determining the therapeutic potential of targeting members of this receptor superfamily in pathological states, with a particular focus on neurodegenerative diseases.

Education/Training

2016-2020: Lord Kelvin Adam Smith Fellow, Institute of Molecular, Cell and Systems Biology, University of Glasgow

2012-2016: Postdoctoral Researcher (Career Development Fellow), MRC Toxicology Unit, Leicester (principal investigator Prof. Andrew B. Tobin)

2011-2012: Postdoctoral Research Associate, Cell Physiology and Pharmacology, University of Leicester (principal investigator Prof. R.A. John Challiss)

2007-2011: University of Leicester; PhD Cell Physiology and Pharmacology (supervisor Prof. R.A. John Challiss)

My PhD (BBSRC-CASE with GlaxoSmithKline) was focussed on the in vitro characterisation of novel allosteric modulators of the Type 5 metabotropic glutamate receptor (mGluR5). During my PhD, I completed a research placement at GlaxoSmithKline (Harlow, UK).
Regulation and Pharmacological Manipulation of the Type 5 Metabotropic Glutamate (mGlu5) Receptor

2004-2007: University of Leicester; BSc (Hons. 1st class) Cell Physiology and Pharmacology


 

Research interests

My research fits within the Molecular Pharmacology theme in the Institute of Molecular, Cell and System’s Biology, and we are also members of the Centre for Translational Pharmacology which is broadly focussed on determining the mechanism of action of drugs in the context of disease.

Research within my laboratory is focussed on defining the therapeutic potential of G protein-coupled receptors (GPCR) in neurodegenerative diseases, such as Alzheimer’s disease (AD). Specifically, we aim to exploit this family of cell-surface receptors to modulate neuroinflammatory processes, and in doing so, offer an approach for modifying progression of disease.

Working with a network of academic and industrial partners (see; below), we employ an array of experimental approaches which span through novel pharmacology to (chemo)genetic and neurodegenerative disease mouse models:

 

In 2016, I relocated to the University of Glasgow as a Lord Kelvin Adam Smith fellow to establish my independent research group. During this time, I made the significant discovery that activating a member of the GPCR superfamily, M1 muscarinic acetylcholine receptors (M1 mAChRs), can improve learning and memory responses and extend the lifespan of mice with terminal neurodegenerative disease (Bradley et al., J. Clin. Invest., 2017):

Much of our current efforts are focussed on defining the mechanism by which M1 mAChRs can achieve these disease-modifying effects.

Despite the significant interest in the M1 mAChR as a potential therapeutic target for symptomatic treatment in AD, ligands targeting this receptor have been associated with adverse responses, which have hampered success in clinical trials. An approach to overcome these issues is to develop biased ligands that promote M1 mAChR signalling pathways leading to clinically beneficial effects whilst avoiding those which lead to toxic/adverse effects. To elucidate which signalling pathway(s) are important for the beneficial and adverse responses to M1 mAChR ligands in vivo, we generated a phosphorylation-deficient, G protein-biased M1 mutant mouse model, and discovered that phosphorylation-dependent signalling is important in driving clinically relevant responses (Bradley et al., Nat. Chem. Biol. 2020):

 

Team

Dr. Mario Rossi: Postdoctoral Research Associate

After obtaining my PhD in molecular bio-technology at the University of Pisa (Italy), I spent an extensive period of time in the USA as research visiting and then research fellow at the National Institutes of Health (NIH) in Bethesda, Maryland. Since 2017 I have joined the University of Glasgow, Institute of Molecular Cell & Systems Biology, within the laboratories of Dr. Sophie Bradley and Professor Andrew Tobin. 
Through “omics” approaches, bio-molecular techniques and Prion diseased neuronal primary cultures, my research has mainly focused on the neuroprotective effects of positive allosteric modulation of the M1 muscarinic receptor activity “in-vivo” and “in-vitro”.

Hobbies include: Volleyball, Reading, Hiking

Mr. Colin Molloy: Technician

I am an animal technician and my work involves all aspects of having a personal licence - from understanding the law to performing regulated procedures. I have 20 years of experience in performing regulated procedures, including surgeries, and I have expertise in a number of behavioural assays, including elevated plus maze, open field and Y-maze. I am responsible for training of staff in regulated procedures and I maintain and oversee all of our transgenic colonies.

In my spare time I like nothing more than canoeing on a loch.

Miss Miriam Scarpa: PhD student (primary supervisor; 2017-2021)

My name is Miriam Scarpa and I am a PhD student funded by an MRC-CASE studentship in collaboration with Eli Lilly and Company, and supervised by Dr Sophie Bradley, Prof Andrew Tobin and Dr Zeshan Ahmed.
My research focusses on the role of the M1 muscarinic acetylcholine receptor (mAChR) in the progression of neurodegenerative conditions such as Alzheimer’s disease. In particular, I am investigating the role of the phosphorylation-dependent signalling mediated by the M1 mAChR in neuroinflammation and neurodegeneration by using the murine prion disease model of terminal neurodegeneration in combination with a transgenic mouse model expressing a phosphorylation-deficient mutant of the M1 mAChR.
The techniques I have been using range from pharmacological characterisation on CHO cell-lines and primary neuronal cell cultures, animal behavioural studies, biochemical analysis including western blotting and real-time qPCR, and histology.

Miss Sarah Hesse: PhD student (secondary supervisor; 2017-2023)

Miss Jessica Bowden: PhD student (primary supervisor; 2018-2022)

My name is Jessica Bowden, I joined the lab in September 2018 on an MRC iCASE PhD studentship. I am supervised by Dr Sophie Bradley, Dr John Riddell from the Institute of Neuroscience and Psychology, Professor Andrew Tobin, and Dr Keith Phillips from the industrial collaborator, Eli Lilly. In my PhD, I record neural signals from freely-moving mice to investigate the effects of novel drug candidates targeting muscarinic receptors. I spent just over a year at Eli Lilly learning the techniques, and returned to Glasgow in January 2020 to start recording from our models of neurodegenerative disease. In my spare time, I enjoy travelling and bell ringing.

Miss Rebecca Budgett: PhD student (primary supervisor; 2019-2023)

My name is Rebecca Budgett and I am a first year MRS-funded PhD student working in collaboration with Heptares Therapeutics. I am supervised by Dr Sophie Bradley and Professor Andrew Tobin at the University of Glasgow, and Dr Kirstie Bennett at Heptares. My research aims to evaluate the role of the type 5 metabotropic glutamate receptor (mGluR5) in the modulation of neuroinflammation and progression of neurodegenerative disease. In this way, I hope to determine if mGluR5 is a viable drug target in the treatment of neurodegenerative diseases. Outside of the lab I love being outdoors and playing lacrosse. 

Mr Jose Andres Alepuz Guillen: PhD student (secondary supervisor; 2019-2023)

 
My name is Jose Andres Alepuz Guillen and I am a first year PhD student funded with a donation from the Rice family in Scotland.
My project focuses on the role of M1 mAChRs receptors in the infectivity and spreading of neurodegenerative diseases.
I am co-supervised by Professor Andrew Tobin and Dr. Sophie Bradley.

Collaborations

Academic:
Prof. Andrew Tobin (University of Glasgow, UK)
Prof. Graeme Milligan (University of Glasgow, UK)
Dr. Brian Hudson (University of Glasgow, UK)
Prof. Gerard Graham (University of Glasgow, UK)
Dr. John Riddell (University of Glasgow, UK)
Dr. Julia Edgar (University of Glasgow, UK)
Dr. Jonathan Taylor (University of Glasgow, UK)
Dr. Karen Gregory (Monash Institute for Pharmaceutical Sciences, Melbourne, Australia)
Prof. Craig Lindsley, Prof. Jeff Conn and Dr. Jerri Rook (Vanderbilt Center for Neuroscience Drug Discovery, USA)

Industry:
Sosei-Heptares: Medical Research Scotland studentship
Eli Lilly: MRC Industrial Collaboration Award, MRC-CASE studentship, MRC iCASE studentship

Additional Information 

Committees

2020-present: Scottish Dementia Research Consortium Executive Committee
2018-present: British Pharmacological Society Finance Committee

Professional memberships

2018-present: Member of the Scottish Dementia Research Consortium
2018-present: Member of the ARUK Scotland Network
2007-present: Member of the British Pharmacological Society (2007 – present).

Invited speaker invitations:

• Gatsby Introductory Course on Optogenetics and Chemogenetics, Brighton, UK (postponed to 2021)
• Horizons in Neuroscience: Exploring academic advances for industry application, Edinburgh, UK (February 2020).
• COMPARE, University of Nottingham, UK (January 2020).
• European Research Network on Signal Transduction General Meeting, Belfast, UK (October 2019).
• ASPET, EB2019, Orlando Florida, USA (April 2019).
• Vanderbilt Center for Neuroscience Drug Discovery, Nashville, USA (February 2019).
• BPS Winter Meeting, London, UK (December 2018).
• University of Bath Pharmacology Society, Bath, UK (November 2018).
• 15th Asian-Pacific Society for Neurochemistry meeting (ASPN 2018), Macau, China (August 2018).
• ARUK Network Science Day, King’s College London, UK (June 2018).
• 7th Focused Meeting on Cell Signaling, Nottingham, UK (16-17 April 2018). 

• The UK Dementia Research Institute Edinburgh Launch Symposium, Edinburgh, UK (April, 2018).
• Quantum enhanced imaging for biomedical and clinical applications workshop, University of Glasgow (April, 2017). 

• The Newton Fund Workshop on Drug Discovery, Brazil (March, 2016).
• ASCEPT-MPGPCR Joint Scientific Meeting, Melbourne, Australia (December 2016).

Short talks (selected from abstracts):
• Gordon Research Conferences, Molecular Pharmacology, Lucca, Italy (March 2017).
• The Newton Fund Workshop on Drug Discovery, Brazil (March, 2016).
• ASCEPT-MPGPCR Joint Scientific Meeting, Melbourne, Australia (December 2014).
• 6th Focused Meeting on Cell Signalling, Leicester, UK (April 2016). 

• Keystone Symposia, Snowbird Resort, Utah, USA (April 2014).
• 3rd Focused Meeting on Cell Signalling, Leicester, UK (April 2009).

Conference/symposium organization

  • Organiser of British Pharmacological Society symposium at Pharmacology 2019 (Edinburgh, UK).
  • Organiser of a Young Life Scientists’ Symposium 2018 (Glasgow, UK).

Awards

• Gordon Research Conferences travel grant, 2017.
• Animal Welfare and Ethical Review Board 3R’s Prize, University of Glasgow, 2017.
• Oral communication prize, 6th Focused Meeting on Cell Signalling, Leicester, 2016.

• CLARITY workshop, Stanford University, Palo Alto, CA, USA, June 2014. 

• MRC Career Development Fellowship, 2012.
• College of Medicine, Biological Sciences & Psychology PhD Prize, 2011.
• BPS Bain Memorial Fund Bursary, University of Leicester, July 2010.
• Institute of Biology Award, Top Bioscience Student, University of Leicester, 2007.
• The Physiological Society Undergraduate Prize for Physiology, University of Leicester, 2007.
• Cell Physiology and Pharmacology, Joint Laboratory Project Prize, University of Leicester, 2007. 

• Astra Zeneca Physiological and Pharmacology Prize, University of Leicester, 2007.
• Margaret Wallace and Henry Prize, Biological Sciences Graduate of the Year, University of Leicester, 2007.
• Novartis Best Student in Third Year Pharmacology Prize, University of Leicester, 2007.

• Novartis Best Student in Second Year Module BS2014 Prize, University of Leicester, 2006.

Grants

• 2020-2021: Pilot grant
Title: Defining neuroinflammatory responses in prion disease
Awarding body: Alzheimer’s Research UK (ARUK) Scotland Network Centre
Role: Principal investigator
*Collaboration with Professor Gerard Graham

• 2019-2023: PhD studentship
Title: Defining novel targets in neurodegenerative disease
Awarding body: Medical Research Scotland (industrial partner, Sosei-Heptares)
Role: Principal investigator and primary supervisor*
*Co-supervised by Kirstie Bennett (Sosei-Heptares) and Andrew B. Tobin

• 2018-2022: PhD studentship
Title: Targeting muscarinic receptors in treating and slowing the progression of 
neurodegeneration
Awarding body: MRC iCASE (industrial partner, Eli Lilly)
Role: Principal investigator and primary supervisor*
*Co-supervised by John Riddell, Andrew B. Tobin and Keith Phillips (Eli Lilly)

• 2018: Vacation Scholarship
Title: Defining novel G protein coupled receptor targets in neurodegeneration
Awarding body: Medical Research Scotland
Role: Principal investigator

• 2017-2021: PhD studentship
Title: Targeting the M4 muscarinic acetylcholine receptor in neurodegenerative disease
Awarding body: MRC CASE (industrial partner, Eli Lilly)
Role: Co-investigator (50%) and primary supervisor*
*Co-supervised by Andrew B. Tobin, Zeshan Ahmed (Eli Lilly)

• 2017-2023: PhD studentship
Title: Advanced Imaging for Neurodegenerative Disease
Awarding body: MVLS Doctoral Training Programme
Role: Co-investigator and secondary supervisor*
*Co-supervised by Andrew B. Tobin and Jonathan Taylor

• 2017-2021: Medical Research Council Industry Collaboration Agreement
Title: Pharmacological, molecular and cellular mechanisms of muscarinic slowing (modification) of neurodegenerative disease
Awarding body: Medical Research Council
Role: Co-investigator (50%)
*Industrial partner Eli Lilly

• 2017-2018: Research Grant
Title: Development of advanced imaging techniques to interrogate cellular and architectural changes in the brain during neurodegeneration
Awarding body: Royal Society
Role: Principal investigator

• 2016-2020: Lord Kelvin Adam Smith Fellowship
Title: Targeting GPCRs in neurodegeneration
Awarding body: University of Glasgow
Role: Principal investigator

• 2014: International Exchange Scheme
Title: Evaluation of muscarinic acetylcholine receptor models used in drug discovery
Awarding body: Royal Society
Role: Principal investigator
*Funded a research placement at Monash Institute for Pharmaceutical Sciences, Melbourne, Australia (with Christopher J. Langmead)

Publications

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Jump to: 2022 | 2021 | 2020 | 2019 | 2018 | 2017 | 2016 | 2015 | 2014 | 2012 | 2011 | 2010 | 2009
Number of items: 29.

2022

Dwomoh, L. et al. (2022) M1 muscarinic receptor activation reduces the molecular pathology and slows the progression of prion-mediated neurodegenerative disease. Science Signaling, 15(760), eabm3720. (doi: 10.1126/scisignal.abm3720) (PMID:36378750)

Marsango, S. et al. (2022) The M1 muscarinic receptor is present in situ as a ligand-regulated mixture of monomers and oligomeric complexes. Proceedings of the National Academy of Sciences of the United States of America, 119(24), e220110311. (doi: 10.1073/pnas.2201103119) (PMID:35671422) (PMCID:PMC9214538)

Budgett, R. F., Bakker, G., Sergeev, E. , Bennett, K. A. and Bradley, S. J. (2022) Targeting the type 5 metabotropic glutamate receptor: a potential therapeutic strategy for neurodegenerative diseases? Frontiers in Pharmacology, 13, 893422. (doi: 10.3389/fphar.2022.893422) (PMID:35645791) (PMCID:PMC9130574)

2021

Scarpa, M. et al. (2021) Biased M1 muscarinic receptor mutant mice show accelerated progression of prion neurodegenerative disease. Proceedings of the National Academy of Sciences of the United States of America, 118(50), e2107389118. (doi: 10.1073/pnas.2107389118) (PMID:34893539) (PMCID:PMC8685681)

Brown, A. J.H. et al. (2021) From structure to clinic: design of a muscarinic M1 receptor agonist with potential to treatment of Alzheimer’s disease. Cell, 184(24), 5886-5901.e22. (doi: 10.1016/j.cell.2021.11.001) (PMID:34822784)

Bourgognon, J.-M. , Spiers, J. G., Robinson, S. W., Scheiblich, H., Glynn, P., Ortori, C., Bradley, S. J. , Tobin, A. B. and Steinert, J. R. (2021) Inhibition of neuroinflammatory nitric oxide signaling suppresses glycation and prevents neuronal dysfunction in mouse prion disease. Proceedings of the National Academy of Sciences of the United States of America, 118(10), e200957911. (doi: 10.1073/pnas.2009579118) (PMID:33653950)

2020

Tobin, A. B. and Bradley, S. J. (2020) Editorial for Advances in G Protein-Coupled Receptor Signal Transduction Special Issue. ACS Pharmacology and Translational Science, 3(2), pp. 169-170. (doi: 10.1021/acsptsci.0c00029) (PMID:32296759)

Bradley, S. J. et al. (2020) Biased M1-muscarinic-receptor-mutant mice inform the design of next-generation drugs. Nature Chemical Biology, 16(3), pp. 240-249. (doi: 10.1038/s41589-019-0453-9) (PMID:32080630)

Scarpa, M., Hesse, S. and Bradley, S. J. (2020) M1 muscarinic acetylcholine receptors: a therapeutic strategy for symptomatic and disease-modifying effects in Alzheimer's disease? In: Langmead, C. J. (ed.) From Structure to Clinical Development: Allosteric Modulation of G Protein-Coupled Receptors. Series: Advances in Pharmacology (88). Elsevier, pp. 277-310. ISBN 9780128201879 (doi: 10.1016/bs.apha.2019.12.003)

Khajehali, E., Bradley, S. , van der Westhuizen, E. T., Molloy, C. , Valant, C., Finlayson, L. , Lindsley, C. W., Sexton, P. M., Tobin, A. B. and Christopoulos, A. (2020) Restoring agonist function at a chemogenetically modified M1 muscarinic acetylcholine receptor. ACS Chemical Neuroscience, 11(24), pp. 4270-4279. (doi: 10.1021/acschemneuro.0c00540) (PMID:33196174)

2019

Thompson, K.J., Khajehali, E., Molloy, C. , Valant, C., Bradley, S.J. , Sexton, P.M., Christopoulos, A. and Tobin, A.B. (2019) The In Vitro Characterisation of DREADD Agonist 21, a Novel Ligand for Muscarinic DREADD Receptors. British Journal of Pharmacology 176(16): 3002-3003. Selected Abstract from Pharmacology 2018, London, UK, 18-20 Dec 2018. (doi: 10.1111/bph.14681)

Bolognini, D. et al. (2019) Chemogenetics defines receptor-mediated functions of short chain free fatty acids. Nature Chemical Biology, 15(5), pp. 489-498. (doi: 10.1038/s41589-019-0270-1) (PMID:30992568)

2018

Thompson, K. J. et al. (2018) DREADD agonist 21 is an effective agonist for muscarinic-based DREADDs in vitro and in vivo. ACS Pharmacology and Translational Science, 1(1), pp. 61-72. (doi: 10.1021/acsptsci.8b00012) (PMID:30868140) (PMCID:PMC6407913)

Bourgognon, J.-M. , Spiers, J. G., Scheiblich, H., Antonov, A., Bradley, S. J. , Tobin, A. B. and Steinert, J. R. (2018) Alterations in neuronal metabolism contribute to the pathogenesis of prion disease. Cell Death and Differentiation, 25(8), pp. 1408-1425. (doi: 10.1038/s41418-018-0148-x) (PMID:29915278) (PMCID:PMC6113283)

Bradley, S. J. , Tobin, A. B. and Prihandoko, R. (2018) Muscarinic acetylcholine receptors in the central nervous system. Neuropharmacology, 136(Part C), p. 361. (doi: 10.1016/j.neuropharm.2018.06.012) (PMID:29894772)

Bradley, S. J. , Tobin, A. B. and Prihandoko, R. (2018) The use of chemogenetic approaches to study the physiological roles of muscarinic acetylcholine receptors in the central nervous system. Neuropharmacology, 136(Part C), pp. 421-426. (doi: 10.1016/j.neuropharm.2017.11.043) (PMID:29191752)

Bradley, S. J. et al. (2018) Bitopic binding mode of an M1 muscarinic acetylcholine receptor agonist associated with adverse clinical trial outcomes. Molecular Pharmacology, 93(6), pp. 645-656. (doi: 10.1124/mol.118.111872) (PMID:29695609) (PMCID:PMC5963591)

2017

Bradley, S. J. et al. (2017) M1 muscarinic allosteric modulators slow prion neurodegeneration and restore memory loss. Journal of Clinical Investigation, 127(2), pp. 487-499. (doi: 10.1172/JCI87526) (PMID:27991860) (PMCID:PMC5272187)

2016

Butcher, A. J. et al. (2016) An antibody biosensor establishes the activation of the M1 muscarinic acetylcholine receptor during learning and memory. Journal of Biological Chemistry, 291(17), pp. 8862-8875. (doi: 10.1074/jbc.M115.681726) (PMID:26826123) (PMCID:PMC4861454)

Bradley, S. J. et al. (2016) Mapping physiological G protein-coupled receptor signaling pathways reveals a role for receptor phosphorylation in airway contraction. Proceedings of the National Academy of Sciences of the United States of America, 113(16), pp. 4524-4529. (doi: 10.1073/pnas.1521706113) (PMID:27071102) (PMCID:PMC4843461)

Bradley, S. J. and Tobin, A. B. (2016) Design of next-generation G protein–coupled receptor drugs: linking novel pharmacology and in vivo animal models. Annual Review of Pharmacology and Toxicology, 56(1), pp. 535-559. (doi: 10.1146/annurev-pharmtox-011613-140012) (PMID:26738479)

2015

Prihandoko, R., Bradley, S. J. , Tobin, A. and Butcher, A. J. (2015) Determination of GPCR phosphorylation status: establishing a phosphorylation barcode. Current Protocols in Pharmacology, 69, 2.13.1-2.13.26. (doi: 10.1002/0471141755.ph0213s69) (PMID:26344213)

2014

Bradley, S. J. , Riaz, S. A. and Tobin, A. (2014) Employing novel animal models in the design of clinically efficacious GPCR ligands. Current Opinion in Cell Biology, 27, pp. 117-125. (doi: 10.1016/j.ceb.2013.12.002) (PMID:24680437) (PMCID:PMC3989050)

2012

Bradley, S. J. and Challiss, R.A. J. (2012) G protein-coupled receptor signalling in astrocytes in health and disease: A focus on metabotropic glutamate receptors. Biochemical Pharmacology, 84(3), pp. 249-259. (doi: 10.1016/j.bcp.2012.04.009) (PMID:22531220)

2011

Bradley, S.J. and Challiss, R.A.J. (2011) Defining protein kinase/phosphatase isoenzymic regulation of mGlu5receptor-stimulated phospholipase C and Ca2+ responses in astrocytes. British Journal of Pharmacology, 164(2b), pp. 755-771. (doi: 10.1111/j.1476-5381.2011.01421.x) (PMID:21486279) (PMCID:PMC3188889)

Bradley, S. J. , Langmead, C. J., Watson, J. M. and Challiss, R.A. J. (2011) Quantitative analysis reveals multiple mechanisms of allosteric modulation of the mGlu5 receptor in rat astroglia. Molecular Pharmacology, 79(5), pp. 874-885. (doi: 10.1124/mol.110.068882) (PMID:21321061) (PMCID:PMC3082933)

Frank, R. A.W. et al. (2011) Clustered coding variants in the glutamate receptor complexes of individuals with schizophrenia and bipolar disorder. PLoS ONE, 6(4), e19011. (doi: 10.1371/journal.pone.0019011) (PMID:21559497) (PMCID:PMC3084736)

2010

Coopman, K., Huang, Y., Johnston, N., Bradley, S. J. , Wilkinson, G. F. and Willars, G. B. (2010) Comparative effects of the endogenous agonist glucagon-like peptide-1 (GLP-1)-(7-36) amide and the small-molecule ago-allosteric agent "compound 2" at the GLP-1 receptor. Journal of Pharmacology and Experimental Therapeutics, 334(3), pp. 795-808. (doi: 10.1124/jpet.110.166009) (PMID:20507928) (PMCID:PMC2939672)

2009

Bradley, S. J. , Watson, J. M. and Challiss, R.A. J. (2009) Effects of positive allosteric modulators on single-cell oscillatory Ca2+ signaling initiated by the type 5 metabotropic glutamate receptor. Molecular Pharmacology, 76(6), pp. 1302-1313. (doi: 10.1124/mol.109.059170) (PMID:19737913) (PMCID:PMC2784724)

This list was generated on Thu Nov 21 03:03:25 2024 GMT.
Jump to: Articles | Book Sections | Conference or Workshop Item
Number of items: 29.

Articles

Dwomoh, L. et al. (2022) M1 muscarinic receptor activation reduces the molecular pathology and slows the progression of prion-mediated neurodegenerative disease. Science Signaling, 15(760), eabm3720. (doi: 10.1126/scisignal.abm3720) (PMID:36378750)

Marsango, S. et al. (2022) The M1 muscarinic receptor is present in situ as a ligand-regulated mixture of monomers and oligomeric complexes. Proceedings of the National Academy of Sciences of the United States of America, 119(24), e220110311. (doi: 10.1073/pnas.2201103119) (PMID:35671422) (PMCID:PMC9214538)

Budgett, R. F., Bakker, G., Sergeev, E. , Bennett, K. A. and Bradley, S. J. (2022) Targeting the type 5 metabotropic glutamate receptor: a potential therapeutic strategy for neurodegenerative diseases? Frontiers in Pharmacology, 13, 893422. (doi: 10.3389/fphar.2022.893422) (PMID:35645791) (PMCID:PMC9130574)

Scarpa, M. et al. (2021) Biased M1 muscarinic receptor mutant mice show accelerated progression of prion neurodegenerative disease. Proceedings of the National Academy of Sciences of the United States of America, 118(50), e2107389118. (doi: 10.1073/pnas.2107389118) (PMID:34893539) (PMCID:PMC8685681)

Brown, A. J.H. et al. (2021) From structure to clinic: design of a muscarinic M1 receptor agonist with potential to treatment of Alzheimer’s disease. Cell, 184(24), 5886-5901.e22. (doi: 10.1016/j.cell.2021.11.001) (PMID:34822784)

Bourgognon, J.-M. , Spiers, J. G., Robinson, S. W., Scheiblich, H., Glynn, P., Ortori, C., Bradley, S. J. , Tobin, A. B. and Steinert, J. R. (2021) Inhibition of neuroinflammatory nitric oxide signaling suppresses glycation and prevents neuronal dysfunction in mouse prion disease. Proceedings of the National Academy of Sciences of the United States of America, 118(10), e200957911. (doi: 10.1073/pnas.2009579118) (PMID:33653950)

Tobin, A. B. and Bradley, S. J. (2020) Editorial for Advances in G Protein-Coupled Receptor Signal Transduction Special Issue. ACS Pharmacology and Translational Science, 3(2), pp. 169-170. (doi: 10.1021/acsptsci.0c00029) (PMID:32296759)

Bradley, S. J. et al. (2020) Biased M1-muscarinic-receptor-mutant mice inform the design of next-generation drugs. Nature Chemical Biology, 16(3), pp. 240-249. (doi: 10.1038/s41589-019-0453-9) (PMID:32080630)

Khajehali, E., Bradley, S. , van der Westhuizen, E. T., Molloy, C. , Valant, C., Finlayson, L. , Lindsley, C. W., Sexton, P. M., Tobin, A. B. and Christopoulos, A. (2020) Restoring agonist function at a chemogenetically modified M1 muscarinic acetylcholine receptor. ACS Chemical Neuroscience, 11(24), pp. 4270-4279. (doi: 10.1021/acschemneuro.0c00540) (PMID:33196174)

Bolognini, D. et al. (2019) Chemogenetics defines receptor-mediated functions of short chain free fatty acids. Nature Chemical Biology, 15(5), pp. 489-498. (doi: 10.1038/s41589-019-0270-1) (PMID:30992568)

Thompson, K. J. et al. (2018) DREADD agonist 21 is an effective agonist for muscarinic-based DREADDs in vitro and in vivo. ACS Pharmacology and Translational Science, 1(1), pp. 61-72. (doi: 10.1021/acsptsci.8b00012) (PMID:30868140) (PMCID:PMC6407913)

Bourgognon, J.-M. , Spiers, J. G., Scheiblich, H., Antonov, A., Bradley, S. J. , Tobin, A. B. and Steinert, J. R. (2018) Alterations in neuronal metabolism contribute to the pathogenesis of prion disease. Cell Death and Differentiation, 25(8), pp. 1408-1425. (doi: 10.1038/s41418-018-0148-x) (PMID:29915278) (PMCID:PMC6113283)

Bradley, S. J. , Tobin, A. B. and Prihandoko, R. (2018) Muscarinic acetylcholine receptors in the central nervous system. Neuropharmacology, 136(Part C), p. 361. (doi: 10.1016/j.neuropharm.2018.06.012) (PMID:29894772)

Bradley, S. J. , Tobin, A. B. and Prihandoko, R. (2018) The use of chemogenetic approaches to study the physiological roles of muscarinic acetylcholine receptors in the central nervous system. Neuropharmacology, 136(Part C), pp. 421-426. (doi: 10.1016/j.neuropharm.2017.11.043) (PMID:29191752)

Bradley, S. J. et al. (2018) Bitopic binding mode of an M1 muscarinic acetylcholine receptor agonist associated with adverse clinical trial outcomes. Molecular Pharmacology, 93(6), pp. 645-656. (doi: 10.1124/mol.118.111872) (PMID:29695609) (PMCID:PMC5963591)

Bradley, S. J. et al. (2017) M1 muscarinic allosteric modulators slow prion neurodegeneration and restore memory loss. Journal of Clinical Investigation, 127(2), pp. 487-499. (doi: 10.1172/JCI87526) (PMID:27991860) (PMCID:PMC5272187)

Butcher, A. J. et al. (2016) An antibody biosensor establishes the activation of the M1 muscarinic acetylcholine receptor during learning and memory. Journal of Biological Chemistry, 291(17), pp. 8862-8875. (doi: 10.1074/jbc.M115.681726) (PMID:26826123) (PMCID:PMC4861454)

Bradley, S. J. et al. (2016) Mapping physiological G protein-coupled receptor signaling pathways reveals a role for receptor phosphorylation in airway contraction. Proceedings of the National Academy of Sciences of the United States of America, 113(16), pp. 4524-4529. (doi: 10.1073/pnas.1521706113) (PMID:27071102) (PMCID:PMC4843461)

Bradley, S. J. and Tobin, A. B. (2016) Design of next-generation G protein–coupled receptor drugs: linking novel pharmacology and in vivo animal models. Annual Review of Pharmacology and Toxicology, 56(1), pp. 535-559. (doi: 10.1146/annurev-pharmtox-011613-140012) (PMID:26738479)

Prihandoko, R., Bradley, S. J. , Tobin, A. and Butcher, A. J. (2015) Determination of GPCR phosphorylation status: establishing a phosphorylation barcode. Current Protocols in Pharmacology, 69, 2.13.1-2.13.26. (doi: 10.1002/0471141755.ph0213s69) (PMID:26344213)

Bradley, S. J. , Riaz, S. A. and Tobin, A. (2014) Employing novel animal models in the design of clinically efficacious GPCR ligands. Current Opinion in Cell Biology, 27, pp. 117-125. (doi: 10.1016/j.ceb.2013.12.002) (PMID:24680437) (PMCID:PMC3989050)

Bradley, S. J. and Challiss, R.A. J. (2012) G protein-coupled receptor signalling in astrocytes in health and disease: A focus on metabotropic glutamate receptors. Biochemical Pharmacology, 84(3), pp. 249-259. (doi: 10.1016/j.bcp.2012.04.009) (PMID:22531220)

Bradley, S.J. and Challiss, R.A.J. (2011) Defining protein kinase/phosphatase isoenzymic regulation of mGlu5receptor-stimulated phospholipase C and Ca2+ responses in astrocytes. British Journal of Pharmacology, 164(2b), pp. 755-771. (doi: 10.1111/j.1476-5381.2011.01421.x) (PMID:21486279) (PMCID:PMC3188889)

Bradley, S. J. , Langmead, C. J., Watson, J. M. and Challiss, R.A. J. (2011) Quantitative analysis reveals multiple mechanisms of allosteric modulation of the mGlu5 receptor in rat astroglia. Molecular Pharmacology, 79(5), pp. 874-885. (doi: 10.1124/mol.110.068882) (PMID:21321061) (PMCID:PMC3082933)

Frank, R. A.W. et al. (2011) Clustered coding variants in the glutamate receptor complexes of individuals with schizophrenia and bipolar disorder. PLoS ONE, 6(4), e19011. (doi: 10.1371/journal.pone.0019011) (PMID:21559497) (PMCID:PMC3084736)

Coopman, K., Huang, Y., Johnston, N., Bradley, S. J. , Wilkinson, G. F. and Willars, G. B. (2010) Comparative effects of the endogenous agonist glucagon-like peptide-1 (GLP-1)-(7-36) amide and the small-molecule ago-allosteric agent "compound 2" at the GLP-1 receptor. Journal of Pharmacology and Experimental Therapeutics, 334(3), pp. 795-808. (doi: 10.1124/jpet.110.166009) (PMID:20507928) (PMCID:PMC2939672)

Bradley, S. J. , Watson, J. M. and Challiss, R.A. J. (2009) Effects of positive allosteric modulators on single-cell oscillatory Ca2+ signaling initiated by the type 5 metabotropic glutamate receptor. Molecular Pharmacology, 76(6), pp. 1302-1313. (doi: 10.1124/mol.109.059170) (PMID:19737913) (PMCID:PMC2784724)

Book Sections

Scarpa, M., Hesse, S. and Bradley, S. J. (2020) M1 muscarinic acetylcholine receptors: a therapeutic strategy for symptomatic and disease-modifying effects in Alzheimer's disease? In: Langmead, C. J. (ed.) From Structure to Clinical Development: Allosteric Modulation of G Protein-Coupled Receptors. Series: Advances in Pharmacology (88). Elsevier, pp. 277-310. ISBN 9780128201879 (doi: 10.1016/bs.apha.2019.12.003)

Conference or Workshop Item

Thompson, K.J., Khajehali, E., Molloy, C. , Valant, C., Bradley, S.J. , Sexton, P.M., Christopoulos, A. and Tobin, A.B. (2019) The In Vitro Characterisation of DREADD Agonist 21, a Novel Ligand for Muscarinic DREADD Receptors. British Journal of Pharmacology 176(16): 3002-3003. Selected Abstract from Pharmacology 2018, London, UK, 18-20 Dec 2018. (doi: 10.1111/bph.14681)

This list was generated on Thu Nov 21 03:03:25 2024 GMT.

Grants

Grants and Awards listed are those received whilst working with the University of Glasgow.

  • Defining neuroinflammatory responses in prion disease
    Alzheimer`s Research UK
    2020 - 2021
     
  • Defining novel targets in neurodegenerative disease
    Medical Research Scotland
    2019 - 2023
     
  • Assessing the effect of targeting the M1 muscarinic receptor in a mouse model of Alzheimer¿s disease
    Alzheimer`s Research UK Scotland Network Centre
    2019 - 2020
     
  • MICA Pharmacological, molecular and cellular mechanisms of muscarinic slowing (modification) of neurodegenerative disease.
    Medical Research Council
    2017 - 2021
     
  • Development of advanced imaging techniques to interrogate cellular and architectual changes in the brain in neurodegenerative disease
    The Royal Society
    2017 - 2018
     

Supervision

  • Miss Miriam Scarpa: PhD student (primary supervisor; 2017-2021)
  • Miss Sarah Hesse: PhD student (secondary supervisor; 2017-2023)
  • Miss Jessica Bowden: PhD student (primary supervisor; 2018-2022)
  • Miss Rebecca Budgett: PhD student (primary supervisor; 2019-2023)
  • Mr Jose Andres Alepuz Guillen: PhD student (secondary supervisor; 2019-2023

Research datasets

Jump to: 2022 | 2021
Number of items: 2.

2022

Marsango, S., Jenkins, L. , Pediani, J. , Bradley, S. , Ward, R., Hesse, S. and Milligan, G. (2022) The M1 muscarinic receptor is present in situ as a ligand-regulated mixture of monomers and oligomeric complexes. [Data Collection]

2021

Scarpa, M., Molloy, C. , Jenkins, L. , Strellis, B., Budgett, R., Hesse, S., Dwomoh, L. , Marsango, S., Tejeda, G. , Rossi, M., Ahmed, Z., Milligan, G. , Hudson, B. , Tobin, A. , Bradley, S. and Heptares, S. (2021) Biased M1 muscarinic receptor mutant mice show accelerated progression of prion neurodegenerative disease. [Data Collection]

This list was generated on Thu Nov 21 03:03:27 2024 GMT.

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