People

Professor John Challiss

Professor of Molecular and Cellular Pharmacology; Head of Department

School/Department: Molecular Cell Biology, Department of

Telephone: 0116(0) 229 7146

Email: jc36@leicester.ac.uk

Profile

I am a molecular pharmacologist specialising in research into the signal transduction mechanisms that connect events at the cell-surface (ligand-receptor binding) to altered cell responses in both health and disease. I have published >200 original research papers and a number of highly cited reviews (see Google Scholar: http://scholar.google.co.uk/citations?hl=en&user=TeVsJCkAAAAJ).

I have a degree in Biochemistry (BSc (Hons) University of Bath) and doctorate in metabolic regulation (DPhil University of Oxford). Following post-doctoral research into applying NMR spectroscopy to understand muscle bioenergetics I joined the University of Leicester initially as a Wellcome Trust-funded research lecturer and subsequently as Senior Lecturer Reader and Professor (Chair in 2003). I am presently Head of Department (since October 2017).

My research contributions have been recognised by the award of a fellowship (FBPhS 2016) by the British Pharmacological Society. I also hold a Fellowship (FHEA 2016) from Advance-HE. 

Research

My research has been supported by a number of funding bodies including the Wellcome Trust British Heart Foundation UKRI (MRC BBSRC) and the European Commission funders. I have been an academic partner in successful industrial collaborations (e.g. with GlaxoSmithKline). Present research projects include:

1. Understanding signal transduction and metabolism in astrocytes. How are metabolic flux-generating steps regulated by extracellular cues and can this new knowledge be used to target phenotypic alterations that occur in cancer (glioma/glioblastoma)? [in collaboration with Dr Paul Glynn]

2. Alterations to G protein-coupled receptor (GPCR) signalling brought about by G protein-coupled receptor kinases (GRKs) and arrestin proteins. With a focus on the cardiovascular system how does GRK-dependent phosphorylation of different GPCRs lead to arrestin recruitment and whether this causes a cessation of signalling (desensitization/internalization) or a second phase of signalling by the receptor (e.g. the formation of arrestin-dependent signalling scaffolds)? [in collaboration with Dr Jon Willets] 

Publications

(0) Selected Publications

Bradley SJ et al. (2020) Biased M1-muscarinic receptor mutant mice inform design of next-generation drugs. Nat Chem Biol 16, 240-249 (doi: 10.1038/s41589-019-0453-9)

Rainbow RD et al. (2018) Small molecule G protein-coupled receptor kinase inhibitors attenuate GRK2-mediated desensitization of vasoconstrictor-induced arterial contractions. Mol Pharmacol 94, 1079-1091 (doi: 10.1124/mol.118.112524)

Robinson SW et al. (2018) Nitric oxide-mediated post-translational modifications control neurotransmitter release by modulating complexin farnesylation and enhancing its clamping ability. PLoS Biol 16, e2003611 (doi: org/10.1371/journal.pbio.2003611)

Di Candia L et al. (2017) HMGB1 is up-regulated in the airways in asthma and potentiates airway smooth muscle contraction via TLR4. J Allergy Clin Immunol 140, 584-587.e8 (doi: 10.1016/j.jaci.2016.11.049)

Jackson R et al. (2016) Distinct and complementary roles for α and β isoenzymes of protein kinase C in mediating vasoconstrictor responses to acutely elevated glucose. Br J Pharmacol 173, 870-887 (doi: 10.1111/bph.13399)

Bourgognon JM et al. (2013) Regulation of neuronal plasticity and fear by a dynamic change in PAR1-G protein coupling in the amygdala. Mol Psychiatry 18, 1136-1145 (doi: 10.1038/mp.2012.133)

Sutcliffe A et al. (2012) Increased nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) expression mediates intrinsic airway smooth muscle hyper-contractility in asthma. Am J Respir Crit Care Med 185, 267-274 (doi: 10.1164/rccm.201107-1281OC)

Nelson CP et al. (2011) Principal role of adenylyl cyclase 6 in K+-channel regulation and vasodilator signalling in vascular smooth muscle cells. Cardiovasc Res 91, 694-702 (doi: 10.1093/cvr/cvr137)

Bradley SJ et al. (2011) Quantitative analysis reveals multiple mechanisms of allosteric modulation of the mGlu5 receptor in rat astroglia. Mol Pharmacol 79, 874-885 (doi: 10.1124/mol.110.068882)

Morris GE et al. (2011) G protein-coupled receptor kinase2 and arrestin2 regulate arterial smooth muscle P2Y-purinoceptor signalling. Cardiovasc Res 89, 193-203 (doi: 10.1093/cvr/cvq249).

Supervision

I have supervised 32 students to successful completion of PhDs as well as numerous other students undertaking lab-based research projects (MRes MSc iBSc undergraduate). I would be happy to supervise new doctoral students interested in pursuing research projects in the following areas:

1. Understanding signal transduction and metabolism differences in cancer and non-cancerous cells.

2. How do G protein-coupled receptor kinases (GRKs) and arrestin proteins regulate G protein-coupled receptor (GPCR) actions in health and disease? 

Teaching

I am a member of the Physiology Pharmacology and Neuroscience teaching and learning team which is responsible for delivery of Biological Sciences (Physiology and Pharmacology) Biological Sciences (Neuroscience) and Medical Bioscience (Medical Physiology degrees. I teach across all years of the School of Biological Sciences (SoBS) degrees and contribute to 4 modules including one that I convene. In addition I teach within Leicester Medical School (LMS) and offer research projects to SoBS (undergraduate and MSc/MRes)and LMS (iMSc) students.

Press and media

I am a Professor of Molecular and Cellular Pharmacology - I am happy to be contacted about the fundamental cellular mechanisms that underlie the actions of drugs. I am also happy to provide expert comment on new breakthroughs in drug discovery.

Activities

Member Biochemical Society

Member British Pharmacological Society

Member American Society of Pharmacology and Experimental Therapeutics

Member British Society for Cardiovascular Research

Editorial Advisory Board Biochemical Pharmacology

Awards

Fellow British Pharmacological Society (FBPhS)

Fellow Advance-HE (FHEA) 

Qualifications

BSc (1st Class Hons) Biochemistry University of Bath

DPhil Metabolic Biochemistry University of Oxford

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