Edinburgh Research Explorer

Prof Jonathan Seckl

Moncrieff Arnott Chair of Molecular Medicine

Biography

Jonathan Seckl is both medically and scientifically qualified (MBBS UCL, PhD CXWMS, ICL). His main research contribution has been in elucidating the biology and importance of tissue-specific metabolism of glucocorticoids in determining local steroid hormone action and in developmental programming of the brain and body.

Specifically, Seckl and colleagues discovered that a hitherto obscure enzyme, 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1), unexpectedly functions to regenerate active glucocorticoids in brain and periphery, amplifying intracellular action. The group discovered increased expression of 11β-HSD1 in brain with ageing and showed this causes cognitive impairments with age. Analogously they found increased 11β-HSD1 expression in adipose tissue with obesity and showed this produces metabolic syndrome. Seckl and colleagues proposed that inhibition/deletion of 11β-HSD1 may be of utility in metabolic syndrome and age-related cognitive impairments, a concept they established in preclinical and experimental human studies and now in successful phase II trials.

In a related strand, Seckl’s lab originally identified, characterised and isolated a novel isozyme, 11β-HSD type 2, from placenta. This rapidly inactivates glucocorticoids leading the group to advance the ‘glucocorticoid hypothesis’ of developmental programming, suggesting that relative deficiency of placental 11β-HSD2 is one core factor in this biology. They have supported this notion in models and humans, elucidating cell-specific epigenetic mechanisms for life-long changes in gene expression and advancing potential therapeutic manipulations to reverse this important pathogenic mechanism.

Seckl’s research has been supported by a Wellcome Trust Senior Clinical Research Fellowship and renewal, 4 successive programme grants from the Wellcome Trust, and additional programme awards from MRC, Wellcome and HFSP. He has authored over 370 peer-reviewed scientific papers (career citations >33,000, h=93, 80 papers >100 citations). He has given over 200 invited lectures at international meetings including many plenaries and has also talked to schools, teachers, lay audiences and in public fora (including BBC2’s Horizon) on stress, obesity, developmental programming and brain ageing. More than 40 of Seckl’s students have gained PhDs. Seckl holds several patents in the fields of cognitive ageing, diabetes/obesity and Alzheimer’s disease. With his colleague Prof Brian Walker, Seckl has led drug discovery in an academic setting; their novel chemical entity is entering clinical trials.

In Edinburgh, Seckl set up and led the new-build interdisciplinary Molecular Medicine Centre (130 researchers), initiated and led the Centre for the Study of the Ageing Brain (now an MRC Centre), was inaugural Head of the School of Molecular and Clinical Medicine (480 staff), was Executive Dean and Director of Research for the College of Medicine and Veterinary Medicine (850 academic staff, >2000 total staff). He devised the strategy and wrote all the College’s submissions to RAE2008 (1st of 28 submissions in Hospital-based Clinical subjects, top [by 4*] UK Veterinary School, 6th in Neurosciences). He is now Vice-Principal for Planning Resources and Research Policy for the University of Edinburgh.

Seckl has served on grant committees for MRC, Wellcome Trust, TSB, RSE, RS, UK charities and the EU and was a member of the Scottish Government’s Scientific Advisory Committee and an RAE2008 subpanel.  He has been elected to the Councils of the Academy of Medical Sciences and the Society for Endocrinology. Seckl is on the Boards of Edinburgh University’s technology transfer company, ERI, Edinburgh BioQuarter and Health Sciences Scotland.  He advanced and raised MRC funding for the ‘Entrepreneur-in-Residence’ concept and leads Edinburgh’s MRC Developmental Pathway Funding Scheme Pilot Portfolio.

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