Mark, an MRC Clinician Scientist, NICE Scholar and honorary consultant physician in Clinical Pharmacology and General (Internal) Medicine, trained in pre-clinical pharmacology and clinical medicine at Gonville and Caius College, Cambridge. After clinical posts in Cambridge and Nottingham he undertook a PhD in Clinical Pharmacology in Cambridge with Dr Kevin O'Shaughnessy addressing the molecular mechanisms which regulate sodium trafficking in the distal nephron and which contribute to hypertension pathogenesis. Mark is secretary of the MRCP (UK) Therapeutics group, a member of the Prescribing Skills Assessment, is actively involved with therapeutics teaching in Nottingham, contributes to therapeutics textbooks, is a member of the British and European Societies of Hypertension and an associate member of the Higher Education Academy. He has been awarded young investigator prizes from the British Hypertension Society and has presented at meetings in Europe, North America, Asia and Australia.
Hypertension, Toxicology and Therapeutics/Clinical pharmacology
My research group aims to understand how the kidneys regulates human blood pressure and specifically how they do this by reabsorbing sodium salt via pathways sensitive to thiazide diuretic medicines. It is hoped that this understanding will inform the development of new blood pressure lowering medicines which are more effective and better tolerated than the currently available thiazide and thiazide-like diuretics.
High blood pressure (hypertension) affects one in three adults in the UK and is one of the most important reversible risk factors leading to heart attacks and strokes. Thiazide and thiazide-like water tablets (diuretics) are one of the most widely used and cost-effective group of medicines to treat hypertension. They work by causing the kidneys to lose sodium salt into the urine but are usually only partly effective in lowering blood pressure and can cause debilitating side effects, such as those related to low sodium levels in the blood (hyponatraemia).
Together with national and international collaborators Dr Glover's group aims to understand how sodium salt is reabsorbed by the thiazide-sensitive pathway at a molecular level and why severe thiazide-induced hyponatraemia occurs in a minority of patients exposed to these medicines.
What are we doing about
In order to achieve these aims we are conducting genetic and phenotypic studies in two unique patient groups.
The first group have a very rare, inherited and exquisitely thiazide responsive syndrome of hypertension, known as Gordon syndrome (also known as Familial Hyperkalaemic Hypertension or Pseudohypoaldosteronism type 2) but who do not carry mutations established for this condition.
The second group of patients are those admitted to hospital with severe thiazide-induced hyponatraemia and recruitment is already underway at eleven hospitals throughout the UK.
The role or function of identified genes and their mutants are also investigated in the laboratory.
Mark's collaborators include Professors Richard Gordon and Michael Stowasser (University of Queensland), Dr Kevin O'Shaughnessy (University of Cambridge), Professor Stuart Cook and Dr James Ware (Imperial College London), Professor Martin Tobin and Dr Louise Wain (University of Leicester) and Professor Xavier Jeunemaitre (University of Paris Descartes).
Dr Glover's group is supported by a Clinician Scientist Award from the Medical Research Council, grants from the Academy of Medical Sciences, Nottingham University and Nottingham University Hospitals NHS charity, and by the Clinical and Primary Care Research Networks (CLRN and PCRN).
WARE JS, WAIN LV, CHANNAVAJJHALA SK, JACKSON VE, EDWARDS E, LU R, SIEW K, JIA W, SHRINE N, KINNEAR S, JALLAND M, HENRY AP, CLAYTON J, O'SHAUGHNESSY KM, TOBIN MD, SCHUSTER V, COOK S, HALL IP and GLOVER M, 2017. Phenotypic and pharmacogenetic evaluation of patients with thiazide-induced hyponatremia. The Journal of clinical investigation.
CHANNAVAJJHALA S, JIA W, JALLAND M, OʼSHAUGHNESSY K, HALL I and GLOVER M, 2016. Os 08-05 novel molecular insights in urinary exosome protein profiling in thiazide induced hyponatremia. Journal of hypertension. 34 Suppl 1 - ISH 2016 Abstract Book, e69 BARBER, J., MCKEEVER, T.M., MCDOWELL, S.E., CLAYTON, J.A., FERNER, R.E., GORDON, R.D., STOWASSER, M., O'SHAUGHNESSY, K.M., HALL, I.P. and GLOVER, M., 2015. A systematic review and meta-analysis of thiazide-induced hyponatraemia: Time to reconsider electrolyte monitoring regimens after thiazide initiation? British Journal of Clinical Pharmacology. 79(4), 566-577
GLOVER, M., WARE, J.S., HENRY, A., WOLLEY, M., WALSH, R., WAIN, L.V., XU, S., HOFF, W.G.V., TOBIN, M.D., HALL, I.P., COOK, S., GORDON, R.D., STOWASSER, M. and O'SHAUGHNESSY, K.M., 2014. Detection of mutations in KLHL3 and CUL3 in families with fhht (familial hyperkalaemic hypertension or gordon's syndrome) Clinical Science. 126(10), 721-726