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The William Harvey Research Institute - Barts and The London

Professor Morris Brown

Morris

Professor of Endocrine Hypertension

Centre: Clinical Pharmacology

Email: morris.brown@qmul.ac.uk
Telephone: +44(0) 20 7882 3901

Profile

  • Qualified in Classics and Medicine from Cambridge in 1974.
  • Trained in Clinical Pharmacology at Royal Postgraduate Medical School, Hammersmith, MRC Senior Fellow 1982-1985.
  • Foundation Chair of Clinical Pharmacology, Cambridge, 1985-2016.
  • Director of Wellcome Trust Translational Medicine and Therapeutics training programme, 2008-2016.

Memberships and awards

Fellow of the Academy of Medical Sciences, the American Heart Association, the British Pharmacological Society.

  • 1985 Raymond Horton-Smith Prize (Cambridge MD Prize)
  • 2002 Lilly Prize, British Pharmacological Society
  • 2003 Hospital Doctor of the Year 2003
  • 2005 Walter Somerville Medal, British Cardiac Society
  • 2014 Pickering Lecturer, British Hypertension Society
  • 2016 Royal College of Physicians/Lancet Research Award (for ‘outstanding research contributing to excellent patient care’)

Research

Group members

Jackie Salsbury (Clinical trials co-ordinator), Dr Elena Azizan (Royal Society Newton post-doc Fellow), Dr Junhua Zhou (post-doc), Dr Xilin Wu (NIHR Clinical PhD Fellow), Dr Emily Goodchild (BTLC Clinical PhD fellow), Sumedha Garg (visiting BHF PhD student).

Summary 

My research, laboratory and clinical, has sought to discover causes of hypertension, and to optimise its management either by achieving complete cure, e.g. by removal of a hormone-producing adrenal tumour (phaeochromocytoma, Conn's), or by finding the right drug for the right patient. In 1999, I proposed the AB/CD rule, relating choice of treatment to patient's age and plasma renin. As President of the British Hypertension Society 2005-7 I established a research network that won funding from the British Heart Foundation to conduct a series of clinical trials, the 'PATHWAY' programme establishing optimal treatment for different categories of Hypertension. These have been published in Lancet or American journals. My current research is mainly focussed on the adrenal gland, and the small aldosterone-producing adenomas which are a common cause of hypertension – unrecognised in 99% of cases. We discovered a sub-type of these with hallmark somatic mutations, often presenting with resistant hypertension. There diagnosis has been facilitated by development of a PET CT (using 11C-metomidate) that lights up even the tiniest (4-5 mm) nodules, often in patients whose conventional CT of the adrenals was normal. In an NIHR project, we are comparing our PET CT with the invasive test of adrenal vein sampling, for their accuracy in predicting cure of hypertension by adrenalectomy. In a BHF-funded project, we are evaluating a less invasive alternative to surgery, namely ultrasound guided endoscopic radiofrequency ablation of the adenoma.

11C-metomidate PET CT of a left adrenal aldosterone-producing

 

Key Publications

  • Barnes P, Fitzgerald GA, Brown MJ and Dollery CT. Nocturnal asthma and changes in circulating epinephrine, histamine and cortisol. N Engl J Med 303: 263-266. 1980. http://www.nejm.org/doi/full/10.1056/NEJM198007313030506
  • Brown MJ, Jenner DA, Allison DJ, Lewis PJ and Dollery CT. Increased sensitivity and accuracy of phaeochromocytoma diagnosis achieved by use of plasma adrenaline estimations and a pentolinium suppression test. Lancet 1: 174-177, 1981. http://www.sciencedirect.com/science/article/pii/S0140673681900581
  • Brown MJ, Brown DC and Murphy MB. Hypokalaemia from beta-2 receptor stimulation by circulating epinephrine. N Engl J Med 309: 1414-1419, 1983. http://www.nejm.org/doi/full/10.1056/NEJM198312083092303
  • Shawket S, Dickerson C, Hazleman B and Brown MJ. Selective suprasensitivity to CGRP, the potent endogenous vasodilator, in the hands of patients with Raynaud's Phenomenon. The Lancet, ii, 1354-1357, 1989.
  • Dickerson JEC, Hingorani AD, Ashby MJ, Palmer CR and Brown MJ. Optimisation of antihypertensive treatment by crossover rotation of four major classes. Lancet, 353:2008-13, 1999. http://www.sciencedirect.com/science/article/pii/S0140673698076144
  • Brown MJ, Palmer CR, Castaigne A, de Leeuw P, Mancia G, Rosenthal T and Ruilope LM. Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT). Lancet, 356:366-372, 2000. http://www.sciencedirect.com/science/article/pii/S0140673600025277
  • Hood SJ, Taylor K and Brown MJ. The Spironolactone, Amiloride, Losartan and Thiazide (SALT) double-blind crossover trial in patients with low-renin hypertension and elevated aldosterone/renin ratio. Circulation 116: 268-275, 2007.  http://circ.ahajournals.org/content/116/3/268.short
  • Brown MJ, McInnes GT, Papst CC, Zhang J, MacDonald TM. Aliskiren and the calcium channel blocker amlodipine combination as an initial treatment strategy for hypertension control (ACCELERATE): a randomised, parallel-group trial. Lancet. 2011; 377(9762): 312-20. http://www.sciencedirect.com/science/article/pii/S014067361062003X
  • Azizan EA, Poulsen H, Tuluc P, Zhou J, Clausen MV,…….. Dolphin AC, Farooqi IS, Striessnig J, Nissen P, Brown MJ. Somatic mutations in ATP1A1 and CACNA1D underlie a common subtype of adrenal hypertension. Nat Genet. 2013; 45(9): 1055-60. http://www.nature.com/ng/journal/v45/n9/abs/ng.2716.html
  • Williams B, MacDonald TM, Morant S, ……., Brown MJ, British Hypertension Society's Prevention and Treatment of Hypertension with Algorithm-based Therapy Studies Group. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet 2015; 386:2059-206. http://www.sciencedirect.com/science/article/pii/S0140673615002573
  • Teo AED, Garg S, Haris Shaikh L, Zhou J, Karet Frankl FE, Gurnell M, Happerfield L, Marker A, Bienz M, Azizan EAB, Brown MJ. Pregnancy, Primary Aldosteronism, and Adrenal CTNNB1 Mutations. New England Journal of Medicine. 2015; 373:1429-1436. http://www.nejm.org/doi/full/10.1056/NEJMoa1504869
  • Brown MJ, Williams B, Morant S, ……. MacDonald TM. (2015) Amiloride-hydrochlorothiazide versus individual diuretic effects on glucose tolerance and blood pressure (PATHWAY-3): a double-blind randomised trial. Lancet Diabetes Endocrinology 2016; 4:137-147 http://dx.doi.org/10.1016/S2213-8587(15)00377-0.
  • Petruzzelli M, Taylor KP, Koo B, Brown MJ. Telling tails: very high plasma renin levels prompt the diagnosis of renal artery stenosis despite initial negative imaging. Hypertension 2016; 68:11-16. http://www.ncbi.nlm.nih.gov/pubmed/27217414
  • Xie, C.B., Haris Shaikh L, Garg S, Tanriver G, Teo AED, Zhou J, Maniero CM, Zhou W, Kang S, Silverman RB, Azizan EAB, Brown MJ. Regulation of aldosterone secretion by Cav1.3. 2016. Scientific reports 6, 24697. doi: 10.1038/srep24697. http://www.ncbi.nlm.nih.gov/pubmed/27098837
  • Bogman K, Schwab D, Delporte M-L, Palermo G, Amrein K, Mohr S, De Vera Mudry MC, Brown MJ, Ferber P. Pre-clinical and early clinical profile of a highly selective and potent oral inhibitor of aldosterone synthase (CYP11B2). Hypertension. 2017;69:189-196
  • Teo AE, Garg S, Johnson TI, Zhao W, Zhou J, Gomez-Sanchez CE, et al. Physiological and Pathological Roles in Human Adrenal of the Glomeruli-Defining Matrix Protein NPNT (Nephronectin). Hypertension. 2017;69(6):1207-16
  • Maniero C, Garg S, Zhao W, Johnson TI, Zhou J, Gurnell M, Brown MJ. Neurofilament Medium Polypeptide, a Marker for Zona Glomerulosa Cells in Human Adrenal, Inhibits Dopamine D1 Receptor–Mediated Secretion of Aldosterone. Hypertension. 2017; 70: 357-364.

 

Collaborators

Internal

  • Prof William Drake (QMUL/Barts)
  • Dr Chaz Mein (QMUL)
  • Professor Panos Deloukas (QMUL)
  • Dr Peter King (QMUL)

 

External

  • Ms Laila Parvanta (Barts)
  • Prof Annette Dolphin (UCL)
  • Prof Stephen Pereira (UCL)
  • Prof Erik Arstad (UCL)
  • Dr Mark Gurnell (Cambridge)
  • Dr HK Cheow (Cambridge)

BHF PATHWAY Investigators

  • Prof Bryan Williams (UCL)
  • Prof Tom Macdonald (Dundee)
  • Prof Kennedy Cruickshank (KCL)
  • Prof Philip Chowienczyk (KCL)
  • Dr Steve Morant (Dundee)
  • Prof Joerg Striessnig (Innsbruck)
  • Prof Felix Beuschlein (Munich)
  • Prof Akihiko Ito (Kindai, Japan
  • Dr Celso Gomez Sanchez (Mississippi)