Lecturer in Endocrinology/BBSRC New Investigator
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, and was appointed to a lectureship in 2001.
Control of adrenal development and differentiation
Sonic hedgehog and BMP signalling in endocrine systems
Adrenocortical cell signalling and steroidogenesis
Adrenocortical 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 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 mechanisms that control Shh signalling or are downstream of it in the adrenal, and the contribution that Shh makes to 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. The role of primary cilia in adrenal development and function is also under investigation.
More recently we have begun to investigate 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.
Shh (red) is expressed in the subcapsular region of the adrenal gland in relatively undifferentiated cells that do not express the steroidogenic enzymes CYP11B1 (green, lower) or CYP11B2 (green, upper)
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.
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.
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.
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.
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.
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.
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.
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.
King, PJ, Guasti, L and Laufer, E (2008) Hedgehog signalling in endocrine development and disease. J. Endocrinol., 198: 439-450.
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.
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.
King, P, Paul, A and Laufer, E (2009) Shh signaling regulates adrenocortical development and identifies progenitors of steroidogenic lineages. PNAS, 106: 21185-21190.
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.
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.
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.
Laufer, E, Kesper, D, Vortkamp A and King, P (2012) Sonic hedgehog signaling during adrenal development. Mol. Cell. Endocrinol., 351: 19-27.
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.
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.
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.
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)