Dr Jonathon Willets

I originally trained as a biochemist in Liverpool before studying for a PhD in toxicology and pharmacology at the University of Leicester. After my PhD I spent three years as a postdoc at the University of Bristol investigating the molecular processes that regulate G protein-coupled receptor (GPCR) signalling. In 1999 I returned to Leicester to work as a postdoc in Prof Steve Nahorski’s laboratory. I was appointed as a lecturer in reproductive sciences at the University of Leicester in 2006 and promoted to associate professor in 2011. In 2015 I transferred to the Department of Molecular and Cell Biology as Associate Lecturer in molecular pharmacology.

GPCRs are a family of cell surface proteins that decode a plethora of external signals to enable cellular communication. Research focuses on regulation of endogenous GPCR signalling in smooth muscle excitability with relevance to vascular disease. We are interested in two families of proteins GRKs and non-visual arrestins which negatively regulate GPCR signalling and control signalling pathways involved in increasingly diverse cellular processes e.g. migration growth metastasis and hypertension. We combine fluorescent bioprobes/confocal imaging to examine GPCR regulation in ‘real-time’ in primary cell cultures. We routinely utilise molecular manipulations of protein levels or function to determine their involvement in multiple GPCR signalling cascades and physiological outputs. Combining these powerful techniques enables unique identification of specific interactions of individual endogenous GRKs/arrestins (or other proteins) and endogenously expressed receptors often only days after isolation. Recently research has examined the role that GRK and arrestins play in the regulation of MAPK signalling pathways in vascular diseases. 

[1] S. Brennan, S. Chen, S. Makwana, C.A. Martin, M.W. Sims, A.S.A. Alonazi, J.M. Willets, I.B. Squire, R.D. Rainbow, A novel form of glycolytic metabolism-dependent cardioprotection revealed by PKCα and β inhibition, J Physiol 597 (2019) 4481-4501.

[2] R.D. Rainbow, S. Brennan, R. Jackson, A.J. Beech, A. Bengreed, H.V. Waldschmidt, J.J.G. Tesmer, R.A.J. Challiss, J.M. Willets, Small-Molecule G Protein-Coupled Receptor Kinase Inhibitors Attenuate G Protein-Coupled Receptor Kinase 2-Mediated Desensitization of Vasoconstrictor-Induced Arterial Contractions, Mol Pharmacol 94 (2018) 1079-1091.

[3] C.A. Nash, C.P. Nelson, R. Mistry, C. Moeller-Olsen, E. Christofidou, R.A.J. Challiss, J.M. Willets, Differential regulation of β2-adrenoceptor and adenosine A2B receptor signalling by GRK and arrestin proteins in arterial smooth muscle, Cell Signal 51 (2018) 86-98.

[4] M.F. Bird, R. Guerrini, J.M. Willets, J.P. Thompson, G. Calo, D.G. Lambert, Nociceptin/Orphanin FQ (N/OFQ) conjugated to ATTO594: a novel fluorescent probe for the N/OFQ (NOP) receptor, Br J Pharmacol 175 (2018) 4496-4506.

[5] J.M. Willets, C.A. Nash, R.D. Rainbow, C.P. Nelson, R.A. Challiss, Defining the roles of arrestin2 and arrestin3 in vasoconstrictor receptor desensitization in hypertension, Am J Physiol Cell Physiol 309 (2015) C179-89.

[6] J.M. Willets, P.J. Brighton, L.N. Windell, S. Rana, C.A. Nash, J.C. Konje, Bradykinin-activated contractile signalling pathways in human myometrial cells are differentially regulated by arrestin proteins, Mol Cell Endocrinol 407 (2015) 57-66.

[7] G.E. Morris, C.P. Nelson, N.B. Standen, R.A. Challiss, J.M. Willets, Endothelin signalling in arterial smooth muscle is tightly regulated by G protein-coupled receptor kinase 2, Cardiovasc Res 85 (2010) 424-33.

[8] P.J. Brighton, T.H. Marczylo, S. Rana, J.C. Konje, J.M. Willets, Characterization of the endocannabinoid system, CB(1) receptor signalling and desensitization in human myometrium, Br J Pharmacol 164 (2011) 1479-94.

[9] P.J. Brighton, S. Rana, R.J. Challiss, J.C. Konje, J.M. Willets, Arrestins differentially regulate histamine- and oxytocin-evoked phospholipase C and mitogen-activated protein kinase signalling in myometrial cells, Br J Pharmacol 162 (2011) 1603-17.

[10] G.E. Morris, C.P. Nelson, D. Everitt, P.J. Brighton, N.B. Standen, R.A. Challiss, J.M. Willets, G protein-coupled receptor kinase 2 and arrestin2 regulate arterial smooth muscle P2Y-purinoceptor signalling, Cardiovasc Res 89 (2011) 193-203.

[11] G.E. Morris, C.P. Nelson, P.J. Brighton, N.B. Standen, R.A. Challiss, J.M. Willets, Arrestins 2 and 3 differentially regulate ETA and P2Y2 receptor-mediated cell signaling and migration in arterial smooth muscle, Am J Physiol Cell Physiol 302 (2012) C723-34.

PhDs are available in the following areas of research: 1) Investigating the roles that GPCRs play in the development of hypertension 2) Vasoconstrictor-driven vascular smooth muscle proliferation migration and vascular remodelling 3) Effects of glucose and diabetes on arterial smooth muscle function hypertension and vascular remodelling 4) The roles that GPCRs play in regulation of bladder contraction 5) Effects of GRK inhibitors on vascular smooth muscle proliferation migration and vascular remodelling

Biological Sciences/ Medical Physiology/ Pharmacology and Physiology BS1060 Physiology Pharmacology and Neuroscience BS2013 Physiology and Pharmacology (Deputy convenor) MB2080 Pathophysiology of Disease (Module convenor) BS3054 Molecular and Cellular Pharmacology 

G protein coupled receptor signalling Regulation of G protein-coupled receptor signalling Molecular development of hypertension and vascular disease