 |
Centre
for Integrative Physiology |
 |
 | |
          |
| Jonathan Seckl |
|
Centre
for Integrative Physiology |
|
| |
| |
| Jonathan Seckl |
|
CIP links:
|
Personal Profile
ResearchJonathan Seckl is both medically and scientifically trained (MBBS at UCL, PhD in neuroendocrinology at Imperial College London). A clinical endocrinologist and former Wellcome Trust Senior Clinical Research Fellow, Seckl’s research (funded by 4 successive programme grants from the Wellcome Trust, and additional programme awards from MRC and HFSP) focuses on glucocorticoid biology from ‘cloning to clinic’. The laboratory exploits technologies from molecular and cell biology through models in vivo to detailed clinical investigation. The main themes are the discovery and understanding of the importance of local tissue inactivation/regeneration of glucocorticoids (by 11ß-hydroxysteroid dehydrogenases) as a cause of and therapeutic target for age-related memory impairments and the metabolic syndrome-diabetes-obesity continuum. The group also advanced and supported the glucocorticoid hypothesis of fetal ‘programming’ and has elucidated fundamental molecular and epigenetic mechanisms by which this leads to subsequent disorders in adult life. Seckl has authored over 280 peer-reviewed scientific papers (career citations >16,000). He has given over 200 invited lectures at international meetings including many plenary talks. He has also talked to schools, teachers groups, lay audiences and in public fora on obesity, stress, developmental programming and ageing. 34 of Seckl’s students have gained PhDs; most are still active in research, several in leading positions around the globe. Prof Seckl led the new-build interdisciplinary Molecular Medicine Centre (130 researchers), set up the interdisciplinary Centre for the Study of the Ageing Brain (now an MRC Centre), has been head of the Department of Medical Sciences (180 staff), was inaugural Head of School of Molecular and Clinical Medicine (500 staff), and is now Director of Research for the College of Medicine and Veterinary Medicine. He led the preparation of the College’s submissions to RAE2008. He has been on grant awarding committees for the MRC, Wellcome Trust, RSE, other UK charities and the EU and was a member of the Scottish Government’s Scientific Advisory Committee and an RAE2008 subpanel. He is currently on the MRC DPFS Panel and the council of the Academy of Medical Sciences. Seckl holds several patents and is on the Board of Edinburgh University’s technology transfer company, ERI. He advanced and raised MRC funding for the ‘Entrepreneur-in-Residence concept and leads Edinburgh’s MRC Developmental Pathway Funding Scheme Portfolio.
FundingOur research is supported by external grant funding of ~£2M per annum including current Programme Grants from Wellcome Trust, British Heart Foundation, and Medical Research Council. And also a current HFSP programme award with colleagues in Canada and the Netherlands. Team Members
Collaborations
Recent Publications2009 Lucassen PJ, Bosch OJ, Jousma E, Krömer SA, Andrew R, Seckl JR, Neumann ID (2009). Prenatal stress reduces postnatal neurogenesis in rats selectively bred for high, but not low, anxiety: possible key role of placental 11β-hydroxysteroid dehydrogenase type 2. Eur J Neurosci. 29: 97-103 Wyrwoll CS, Seckl JR, Holmes MC (2009). Altered placental function of 11β-HSD2 knockout mice. Endocrinology 150:1287-93 Yehuda R, Bierer LM, Andrew R, Schmeidler J, Seckl JR (2009). Enduring effects of severe developmental adversity, including nutritional deprivation, on cortisol metabolism in aging Holocaust survivors. J Psychiatr Res 43:877-83 de Vries A, Hazlewood L, Fitch PM, Seckl JR, Foster P, Howie SE (2009). High-fat feeding redirects cytokine responses and decreases allergic airway eosinophilia. Clin Exp Allergy 39: 731-739 Goedecke JH, Dave JA, Faulenbach MV, Utzschneider KM, Lambert EV, West S, Collins M, Olsson T, Walker BR, Seckl JR, Kahn SE, Levitt NS (2009). Insulin response in relation to insulin sensitivity: an appropriate beta-cell response in black South African women. Diabetes Care 32: 860-865 Lai M, Bae SE, Bell JE, Seckl JR, Macleod MR (2009). Mineralocorticoid receptor mRNA expression is increased in human hippocampus following brief cerebral ischaemia. Neuropathol Appl Neurobiol 35:156-64 Goedecke JH, Levitt NS, Lambert EV, Utzschneider KM, Faulenbach MV, Dave JA, West S, Victor H, Evans J, Olsson T, Walker BR, Seckl JR, Kahn SE (2009). Differential Effects of Abdominal Adipose Tissue Distribution on Insulin Sensitivity in Black and White South African Women. Obesity 17: 1506-1512. Yehuda R, Bierer LM, Sarapas C, Makotkine I, Andrew R, Seckl JR (2009) Cortisol metabolic predictors of response to psychotherapy for symptoms of PTSD in survivors of the World Trade Center attacks on September 11, 2001. Psychoneuroendocrinology. 2009 May 1 [Epub ahead of print] PMID: 19411143. Kang P, Rogalska J, Walker CA, Burke M, Seckl JR, Macleod MR, Lai M (2009). Injury-induced mineralocorticoid receptor expression involves differential promoter usage: A novel role for the rat MR beta variant. Mol Cell Endocrinol 305: 56-62. Carter R, Paterson JM, Tworowska U, Stenvers DJ, Mullins JJ, Seckl JR, Holmes MC (2009). Hypothalamic-pituitary-adrenal axis abnormalities in response to deletion of 11β-HSD1 is strain dependent. J Neuroendocrinol 2009 Jul 7 [Epub ahead of print] PMID: 19602102 Sai S, Nakagawa Y, Sakaguchi K, Okada S, Takahashi H, Hongo T, Seckl JR, Chapman KE, Ohzeki T (2009). Differential regulation of 11β-hydroxysteroid dehydrogenase-1 by dexamethasone in glucocorticoid-sensitive and -resistant childhood lymphoblastic leukemia. Leuk Res 2009 May 13 [Epub ahead of print] PMID: 19446331 Newbury DF, Winchester L, Addis L, Paracchini S, Buckingham LL, Clark A, Cohen W, Cowie H, Dworzynski K, Everitt A, Goodyer IM, Hennessy E, Kindley AD, Miller LL, Nasir J, O'Hare A, Shaw D, Simkin Z, Simonoff E, Slonims V, Watson J, Ragoussis J, Fisher SE, Seckl JR, Helms PJ, Bolton PF, Pickles A, Conti-Ramsden G, Baird G, Bishop DV, Monaco AP (2009). CMIP and ATP2C2 Modulate Phonological Short-Term Memory in Language Impairment. Am J Hum Genet 2009 Jul 29. [Epub ahead of print] PMID: 19646677 2008 De Sousa Peixoto RA, Turban S, Battle JH, Chapman KE, Seckl JR, Morton NM (2008). Preadipocyte 11β-hydroxysteroid dehydrogenase type 1 is a keto-reductase and contributes to diet-induced visceral obesity in vivo. Endocrinology 149: 1861-1868. Sai S, Esteves CL, Kelly V, Michailidou Z, Anderson K, Coll AP, Nakagawa Y, Ohzeki T, Seckl JR, Chapman KE (2008). Glucocorticoid regulation of the promoter of 11β-hydroxysteroid dehydrogenase type 1 is indirect and requires C/EBPb. Mol Endocrinol 22:2049-60 Li RS, Nakagawa Y, Liu YJ, Fujisawa Y, Sai S, Nakanishi T, Chapman KE, Seckl JR, Ohzeki T (2008). Growth hormone inhibits the 11 beta-Hydroxysteroid dehydrogenase type 1 gene promoter activity via insulin-like growth factor I in HepG2 cells. Horm Metab Res. 40: 286-8. Huh SY, Andrew R, Rich-Edwards JW, Kleinman KP, Seckl JR and Gillman MW (2008). Association between umbilical cord glucocorticoids and blood pressure at age 3 years. BMC Medicine 2008, 6:25 doi:10.1186/1741-7015-6-25. Michailidou Z, Carter RN, Marshall E, Sutherland HG, Brownstein DG, Owen E, Cockett K, Kelly V, Ramage L, Al-Dujaili EA, Ross M, Maraki I, Newton K, Holmes MC, Seckl JR, Morton NM, Kenyon CJ, Chapman KE (2008). Glucocorticoid receptor haploinsufficiency causes hypertension and attenuates hypothalamic-pituitary-adrenal axis and blood pressure adaptions to high-fat diet. FASEB J. 22: 3896-3907 Wamil M, Andrew R, Chapman KE, Street J, Morton NM, Seckl JR (2008). 7-Oxysterols modulate glucocorticoid activity in adipocytes through competition for 11β-hydroxysteroid dehydrogenase type 1. Endocrinology 149: 5909-18 Bailey MA, Paterson JM, Hadoke PW, Wrobel N, Bellamy CO, Brownstein DG, Seckl JR, Mullins JJ (2008) A Switch in the Mechanism of Hypertension in the Syndrome of Apparent Mineralocorticoid Excess. J Am Soc Nephrol 19:47-58 Jarvis S, Moinard C, Robson SK, Sumner BEH, Douglas AJ, Seckl JR, Russell JA, Lawrence AB (2008) Effects of weaning age on the behavioural and neuroendocrine development of piglets. Appl Animal Behav Sci 110: 166-181 O'Regan D, Kenyon CJ, Seckl JR, Holmes MC (2008) Prenatal dexamethasone 'programmes' hypotension, but stress-induced hypertension in adult offspring. J Endocrinol 196:343-352 Ye P, Kenyon CJ, Mackenzie SM, Nichol K, Seckl JR, Fraser R, Connell JM, Davies E (2008) Effects of ACTH, dexamethasone, and adrenalectomy on 11beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) gene expression in the rat central nervous system. J Endocrinol 196:305-311 2007 Adamson KA, Cheetham TD, Kendall-Taylor P, Seckl JR, Pearce SH (2007) The role of the IDDM2 locus in the susceptibility of UK APS1 subjects to type 1 diabetes mellitus. Int J Immunogenet 34:17-21 Clark A, O'hare A, Watson J, Cohen W, Cowie H, Elton R, Nasir J, Seckl JR (2007) Receptive language disorder in childhood: Familial aspects and long term outcomes: Results from a Scottish study. Arch Dis Child 92: 614-619 Deary IJ, Ferguson KJ, Bastin ME, Barrow GWS, Reid LM, Seckl JR, Wardlaw JM, MacLullich AMJ (2007) Skull size and intelligence, and King Robert Bruce's IQ. Intelligence 35: 519-525 De Vries A, Holmes MC, Heijnis A, Seier JV, van Heerden J, Louw J, Wolfe-Coote S, Meaney MJ, Levitt NS and Seckl JR (2007) Prenatal dexamethasone exposure induces changes in offspring cardio-metabolic and hypothalamic–pituitary-adrenal axis function without alteration of birth weight in a non-human primate, the African vervet, Chlorocebus aethiops. J Clin Invest 117: 1058-1067 Lai M, Horsburgh K, Bae SE, Carter RN, Stenvers DJ, Fowler JH, Yau JL, Gomez-Sanchez CE, Holmes MC, Kenyon CJ, Seckl JR, Macleod MR (2007) Forebrain mineralocorticoid receptor overexpression enhances memory, reduces anxiety and attenuates neuronal loss in cerebral ischaemia. Eur J Neurosci 25: 1832-1842 Mairesse J, Lesage J, Breton C, Breant B, Hahn T, Darnaudery M, Dickson SL, Seckl JR, Blondeau B, Vieau D, Maccari S, Viltart O (2007) Maternal stress alters endocrine function of the feto-placental unit in rats. Am J Physiol Endocrinol Metab 292:E1526-1533 Michailidou Z, Coll AP, Kenyon CJ, Morton NM, O'rahilly S, Seckl JR, Chapman KE (2007) Peripheral mechanisms contributing to the glucocorticoid hypersensitivity in proopiomelanocortin null mice treated with corticosterone. J Endocrinol 194: 161-170 Michailidou Z, Jensen MD, Dumesic D, Chapman KE, Seckl JR, Walker BR and Morton NM (2007) Omental fat 11ß-HSD-1, but not GR, is correlated with fat cell size independently of obesity. Obesity 15:1155-1163 Paterson JM, Holmes MC, Kenyon CJ, Carter R, Mullins JJ, Seckl JR (2007) Liver-selective transgene rescue of hypothalamic-pituitary-adrenal axis dysfunction in 11ß-hydroxysteroid dehydrogenase type 1 deficient mice. Endocrinology 148:961-966 Sheward WJ, Maywood ES, French KL, Horn JM, Hastings MH, Seckl JR, Holmes MC, Harmar AJ (2007) Entrainment to feeding but not to light: circadian phenotype of VPAC2 receptor-null mice. J Neurosci 27: 4351-4358 Thiesson HC, Jensen BL, Bistrup C, Ottosen PD, McNeilly AD, Andrew R, Seckl JR, Skott O (2007) Renal sodium retention in cirrhotic rats depends on glucocorticoid-mediated activation of the mineralocorticoid receptor due to decreased renal 11beta-HSD2 activity. Am J Physiol Regul Integr Comp Physiol 292: R625-R636 Webster SP, Ward P, Binnie M, Craigie E, McConnell KM, Sooy K, Vinter A, Seckl JR, Walker BR (2007) Discovery and biological evaluation of adamantyl amide 11beta-HSD1 inhibitors. Bioorg Med Chem Lett 17: 2838-2843 Yau JL, Noble J, Thomas S, Kerwin R, Morgan PE, Lightman S, Seckl JR, Pariante CM (2007) The Antidepressant Desipramine Requires the ABCB1 (Mdr1)-Type p-Glycoprotein to Upregulate the Glucocorticoid Receptor in Mice. Neuropsychopharmacology. Mar 14; [Epub ahead of print]. Yau JLW, McNair KM, Noble J, Brownstein D, Hibberd C, Morton N, Mullins JJ, Morris RGM, Cobb S, Seckl JR (2007) Enhanced hippocampal long-term potentiation and spatial learning in aged 11 beta-hydroxysteroid dehydrogenase type 1 knock-out mice. J Neurosci 27: 10487-10496 Yehuda R, Teicher MH, Seckl JR, Grossman RA, Morris A, Bierer LM (2007) Parental posttraumatic stress disorder as a vulnerability factor for low cortisol trait in offspring of holocaust survivors. Arch Gen Psychiatr 64: 1040-1048
2006 Bruley C, Lyons V, Worsley AGF, Wilde MD, Darlington GD, Morton NM, Seckl JR, Chapman KE (2006) A novel promoter for the 11 beta-hydroxysteroid dehydrogenase type 1 gene is active in lung and is C/EBP alpha independent. Endocrinology 147: 2879-2885 Densmore VS, Morton NM, Mullins JJ, Seckl JR (2006) 11 beta-Hydroxysteroid dehydrogenase type 1 induction in the arcuate nucleus by high-fat feeding: A novel constraint to hyperphagia? Endocrinology 147:4486-4495 Gilmour JS, Coutinho AE, Cailhier JF, Man TY, Clay M, Thomas G, Harris HJ, Mullins JJ, Seckl JR, Savill JS, Chapman KE (2006) Local amplification of Glucocorticoids by 11 beta-hydroxysteroid dehydrogenase type 1 promotes macrophage phagocytosis of apoptotic leukocytes. Journal of Immunology 176:7605-7611 Goedecke JH, Wake DJ, Levitt NS, Lambert EV, Collins MR, Morton NM, Andrew R, Seckl JR, Walker BR (2006) Glucocorticoid metabolism within superficial subcutaneous rather than visceral adipose tissue is associated with features of the metabolic syndrome in South African women. Clinical Endocrinology 65: 81-87 Herbert J, Goodyer IM, Grossman AB, Hastings MH, de Kloet ER, Lightman SL, Lupien SJ, Roozendaal B, Seckl JR (2006) Do corticosteroids damage the brain? Journal of Neuroendocrinology 18: 393-411 Nyirenda MJ, Dean S, Lyons V, Chapman KE, Seckl JR (2006) Prenatal programming of hepatocyte nuclear factor 4 alpha in the rat: a key mechanism in the 'foetal origins of hyperglycaemia'? Diabetologia 49:1412-1420 Paterson JM, Short D, Flatman PW, Seckl JR, Aitken A, Dutia MB (2006) Changes in protein expression in the rat medial vestibular nuclei during vestibular compensation. Journal of Physiology 575: 777-788 Raubenheimer PJ, Young EA, Andrew R, Seckl JR (2006) The role of corticosterone in human hypothalamic-pituitary-adrenal axis feedback. Clinical Endocrinology 65: 22-26 Yau JLW, Noble J, Graham M, Seckl JR (2006) Central administration of a cytochrome P450-7 alpha product 7 alpha-hydroxypregnenolone improves spatial memory retention in cognitively impaired aged rats. Journal of Neuroscience 26:11034-11040
2004 Paterson JM, Morton NM, Fievet C, Kenyon CJ, Holmes MC, Staels B, Seckl JR, Mullins JJ (2004) Metabolic syndrome without obesity: hepatic over-expression of 11ß-hydroxysteroid dehydrogenase type 1 in transgenic mice. Proc Natl Acad Sci USA 101:7088-7093 Sandeep T, Yau JLW, MacLullich AMW, Noble J, Deary I, Walker BR, Seckl JR (2004) Effects of 11beta-hydroxysteroid dehydrogenase inhibition on cognitive function in healthy elderly men and patients with type 2 diabetes. Proc Natl Acad Sci USA 101: 6734-6739 Weaver ICG, Cervoni N, Champagne FA, D’Alessio AC, Sharma S, Seckl JR, Dymov S, Szyf M, Meaney MJ (2004) Epigenetic programming by maternal behavior. Nature Neuroscience 7: 847-854 2003 Masuzaki H, Yamamoto H, Kenyon CJ, Elmquist JK, Morton NM, Paterson JM, Shinyama H, Hamm JK, Kershaw EE, Sharp M, Fleming S, Mullins JJ, Seckl JR, Flier JS (2003) Transgenic Amplification of Glucocorticoid Action in Adipose Tissue Causes High Blood Pressure in Mice. J Clin Invest 112: 83-90
2001 Masuzaki H, Paterson J, Shinyama H, Morton NM, Mullins JJ, Seckl JR, Flier JS (2001) A Transgenic Model of Visceral Obesity and the Metabolic Syndrome. Science 294: 2166-2170 Yau JLW, Noble J, Kenyon CJ, Hibberd C, Kotelevtsev Y, Mullins JJ, Seckl JR (2001) Lack of tissue glucocorticoid reactivation in 11ß-hydroxysteroid dehydrogenase type 1 knockout mice ameliorates age-related learning impairments. Proc Natl Acad Sci USA 98: 4716-4721
|
|||||||||
| ___________________________________________ Designed and published by Marianne Eastwood (m.eastwood@ed.ac.uk) © The University of Edinburgh Updated 19 August2009 |
||||||||||
|
|
