Senior Lecturer in Endocrinology
Peter King graduated from Cambridge University with a degree in Natural Sciences. He was awarded a PhD by the Imperial Cancer Research Fund (now CRUK) on transcriptional regulation of the human beta interferon gene, with studies performed at Lincolns Inn Fields and St Georges Hospital Medical School, London. He joined the Molecular Endocrinology Department at Bart’s in 1997, was appointed to a lectureship in 2001 and was promoted to Senior Lecturer in 2009.
- Control of adrenal development and differentiation
- Sonic hedgehog and BMP signalling in endocrine systems
- Adrenocortical cell signalling and steroidogenesis
- Adrenocortical stem cells and cancer stem cells
- Mechanisms of adrenocortical cancer
- Transcriptional regulation in the adrenal cortex
- Transcriptional regulation during adipocyte differentiation
- Control of adipocyte differentiation
Summary of Research
The main aim of my research is to understand the molecular mechanisms that control adrenal development and differentiation during organogenesis, and homeostasis in the adult. The adrenal is a vitally important gland that controls both the stress response and blood volume and, as such, disorders of development and function can be fatal without lifelong therapeutic intervention. Previous research has identified sonic hedgehog (Shh) as an important signalling molecule in adrenal development and has proposed that the cells that produce it and/or the signal receiving cells in the adrenal capsule, are candidates for stem/progenitor cells in development and in the adult. Current research is focussing on potential signalling pathways that control Shh signalling or are downstream of it in the adrenal, for example, Wnt/b catenin, FGF and Dlk1 pathways, and the control that these exert over adrenal remodelling in the adult, which is the concerted response of the gland to stress or changes in blood volume that require the rapid recruitment of new steroidogenic cells. It is anticipated that these will prove to be novel targets for treatment of hypertension.
More recently we have begun to investigate the role of primary cilia (see also Chapple) in adrenal development and function and the shared origins of adrenal and testicular steroidogenic (Leydig) cells, as well as continuing to study signalling pathways that control steroidogenesis and are involved in adrenal cell growth and cancer.
Dlk1 mRNA and DLK1 protein is a marker of the outer ZU. Adult rat adrenal sections were processed for Dlk1 NR-ISH (B) and then stained with antibodies to CYP11B1 (B1) and CYP11B2 (B2) (A, both green). The Dlk1 signal was pseudocoloured to red (C) and the merged image (D) assembled. White arrows indicate CYP11B2 positive/Dlk1 negative cells while the yellow arrows indicate a minority of double positive cells. The same result was obtained with an anti-Dlk1 antibody (inset). Taken from Guasti et al. (2013), Endocrinology 154: 4675-4684.
Members of the Group
PhD students: Dominic Cavlan, Candy Sze.
Noon, LA, Bakmanidis, A, Clark, AJL, O’Shaughnessy, P J and King, P.J (2006) Identification of a novel MC2-R splice variant in murine adipocytes: Implications for post-transcriptional control of expression during adipogenesis. J. Mol. Endocrinol., 37: 415-420. 10.1677/jme.1.02023
Noon, LA, Clark, AJL, O’Shaughnessy, P J. and King, P.J. (2006) A C/EBP site at -87 is required for the activation of a novel murine melanocortin 2-receptor (MC2-R) promoter at late stages during adipogenesis. Endocrinol., 147: 6019-6026. 10.1210/en.2006-0867
Bogdarina, I, Welham, S, King, PJ, Burns, SP and Clark, AJL (2007) Epigenetic modification of the renin-angiotensin system in the fetal programming of hypertension. Circ. Res., 100: 520-526. 10.1161/01.RES.0000258855.60637.58
Johnston, H, King, PJ and O’Shaughnessy, PJ (2007) Effects of ACTH and expression of the melanocortin-2 receptor in the neonatal mouse testis, Reproduction, 133:1181-1187. 10.1530/REP-06-0359
Hu, L, Monteiro, A, Johnston, H, King, P and O'Shaughnessy, PJ (2007) Expression of Cyp21a1 and Cyp11b1 in the fetal mouse testis. Reproduction, 134:585-591. 10.1530/REP-07-0133
Doufexis, M, Storr, HL, King, PJ and Clark, AJL (2007) Interaction of the melanocortin 2 receptor with nucleoporin 50: Evidence for a novel pathway between a G-protein-coupled receptor and the nucleus. FASEB J., 21: 4095-4100. 10.1096/fj.06-7927com
Janes, ME, Chu, KME, Clark, AJL and King, PJ (2008) Mechanisms of adrenocorticotropin-induced activation of ERK1/2 MAP kinase in the human H295R adrenal cell line. Endocrinol., 149: 1898-1905. 10.1210/en.2007-0949
Chung, TT, Webb, TR, Chan, LF, Cooray, SN, Metherell, LA, King, PJ, Chapple, JP and Clark, AJL (2008) The majority of adrenocorticotropin receptor (melanocortin 2 receptor) mutations found in familial glucocorticoid deficiency type 1 lead to defective trafficking of the receptor to the cell surface. J. Clin. Endocrinol. Metab., 93: 4948-4954. 10.1210/jc.2008-1744
King, PJ, Guasti, L and Laufer, E (2008) Hedgehog signalling in endocrine development and disease. J. Endocrinol., 198: 439-450. 10.1677/JOE-08-0161
Bogdarina, IG, King, PJ and Clark, AJL (2009) Characterisation of the angiotensin (AT1b) receptor promoter and its regulation by glucocorticoids. J. Mol. Endocrinol., 43: 73-80. 10.1677/JME-09-0036
Garcia, EA, King, P, Sidhu, K, Ohgusu, H, Walley, A, Lecoeur, C, Gueorguiev, M, Khalaf, S, Davies, D, Grossman, AB, Kojima, M, Petersenn, S, Froguel, P and Korbonits, M (2009) The role of ghrelin and ghrelin-receptor gene variants and promoter activity in type 2 diabetes. Eur. J. Endocrinol., 161: 307-315. 10.1530/EJE-09-0122
King, P, Paul, A and Laufer, E (2009) Shh signaling regulates adrenocortical development and identifies progenitors of steroidogenic lineages. PNAS, 106: 21185-21190. 10.1016/j.ydbio.2009.05.387
Igreja, S, Chahal, HS, King, P, Bolger, GB, Srirangalingam, U, Guasti, L, Chapple, JP, Trivellin, G, Gueorguiev, M, Guegan, K, Stals, K, Khoo, B, Kumar, AV, Ellard, S, Grossman, AB, Korbonits, M. and the International FIPA consortium (2010) Characterization of aryl hydrocarbon receptor interacting protein (AIP) mutations in familial isolated pituitary adenoma families. Human Mutation, 8: 950-960. 10.1002/humu.21292
Guasti, L, Paul, A, Laufer, E and King, P (2011) Localization of Sonic hedgehog secreting and receiving cells in the developing and adult rat adrenal cortex. Mol. Cell. Endocrinol., 336: 117-122. 10.1016/j.mce.2010.11.010
Gorrigan, RJ, Guasti, L, King, P, Clark, AJL and Chan, LF (2011) Localisation of the melanocortin-2-receptor and its accessory proteins in the developing and adult adrenal gland. J. Mol. Endocrinol., 46: 227-232. 10.1530/JME-11-0011
Laufer, E, Kesper, D, Vortkamp A and King, P (2012) Sonic hedgehog signaling during adrenal development. Mol. Cell. Endocrinol., 351: 19-27. 10.1016/j.mce.2011.10.002
Hughes, CR, Guasti, L, Meimaridou, M, Chuang, C-H, Schimenti, JC, King, PJ, Costigan, C, Clark, AJL and Metherell, LA (2012) Mini chromosome maintenance-deficient 4 homologue (MCM4) mutation is associated with adrenal failure, natural killer cell deficiency and increased chromosomal fragility. J. Clin. Invest., 122: 814-820.
Meimaridou, E, Kowalczyk, J, Guasti, L, Hughes, CR, Wagner, F, Frommolt, P, Nürnberg, P, Mann, NP, Banerjee, R, Saka, HN, Chapple, JP, King, PJ, Clark, AJL and Metherell, L.A. (2012) Mutations in nicotinamide nucleotide transhydrogenase (NNT) cause familial glucocorticoid deficiency. Nat. Genet., 44: 740-742. 10.1038/ng.2299
Thompson, IR, Chand, AN, King, PJ, Ansorge, O, Karavitaki, N, Jones, CA, Rahmutula, D, Gardner, DG, Zivkovic, V, Wheeler-Jones, CP, McGonnell, IM, Korbonits, M, Anderson, RA, Wass, JAH, McNeilly, AS and Fowkes, RC (2012) Expression of guanylyl cyclase-B (GC-B/NPR2) receptors in normal human fetal pituitaries and human pituitary adenomas implicates a role for C-type natriuretic peptide. Endoc. Related Cancer, 19: 497-508. 10.1530/ERC-12-0129
Marion, V, Mockel, A, de Melo, C, Obringer, C, Claussmann, A, Simon, A, Messaddeq, N, Durand, M, Dupuis, L, Loeffler, J-P, King, P, Mutter-Schmidt, C, Petrovsky, N, Stoetzel, C and Dollfus, H (2012) BBS-induced ciliary defect enhances adipogenesis, causing paradoxical higher-insulin sensitivity, glucose usage, and decreased inflammatory response. Cell Metab., in press. 10.1016/j.cmet.2012.08.005
Internal: Dr Leo Guasti (WHRI);
External: Dr Ed Laufer (Columbia University, New York, USA); Dr Vincent Marion (University of Strasbourg, France); Prof Peter O’Shaughnessy (Glasgow University).