The primary research interests of Alistair and his colleagues can be described by the general term “bioelectricity”. This ranges from laboratory-based experiments looking at the molecular and cellular properties of ion channel proteins that carry electrical signals across cell membranes to research aimed at improving approaches to measure electrical activity in patients (such as ECGs) in order to facilitate detection of conditions such as atrial fibrillation.
Currently, with many colleagues around the world (in particular Dr Margot Cousin at the Mayo Clinic, Rochester Mn, USA), his group has a major project investigating the mutations in particular potassium ion channels, responsible for a rare but debilitating disease - KCNK9 imprinting syndrome. He has projects on the role and therapeutic importance of related potassium channels in pulmonary hypertension (with Dr Angel Cogolludo and colleagues at the Universidad Complutense de Madrid) and, more generally, on the role of infection in pulmonary vascular diease (iPVD) as part of an international consortium led by Alistair and colleagues Professor Ghazwan Butrous (Pulmonary Vascular Research Institute) and Professor Sir Magdi Yacoub (Imperial College London) doi: 10.21542/gcsp.2019.1.
Alistair’s team has a very successful collaboration with Dr Paul Wright and colleagues at LifeArc Centre for Therapeutics Discovery aiming to discover and investigate novel potassium channel activators for the alleviation of pain. His research team also has several on-going projects on the properties and regulation of other types of ion channels, particularly their potent inhibition by naturally occurring toxins (in collaboration with Professor Murray Selkirk at Imperial College London).
Away from direct ion channel research, Alistair has a major role in a project led by his long–term collaborator, Dr Emma Veale, researching the detection of atrial fibrillation (AF) by clinical pharmacists in primary care and the development of novel approaches to improve AF screening and detection, supported, primarily, by Bayer. This project was the recipient of Healthcare Pioneers awards from the Atrial Fibrillation Association in both 2019 and 2021 and an Excellence in General Practice Pharmacy award from the 2019 Clinical Pharmacy Congress.
Mathie A, Veale EL, Cunningham KP, Holden RG, Wright PD (2021). Two-pore domain potassium channels as drug targets: Anesthesia and beyond. Annu Rev Pharmacol Toxicol 61: 401 - 420. DOI: 10.1146/annurev-pharmtox-030920-111536.
McCoull D, Ococks E, Large JM, Tickle DC, Mathie A, Jerman J, Wright PD (2021). A ‘target-class’ screen to identify activators of two-pore domain potassium (K2P) channels. SLAS Discovery DOI: 10.1177/2472555220976126.
Lalic T, Steponenaite A, Wei L, Vasudevan SR, Mathie A, Peirson SN, Lall GS, Cader MZ (2020). TRESK is a key regulator of nocturnal suprachiasmatic nucleus dynamics and light adaptive responses. Nature Communications 11: 4614 DOI: 10.1038/s41467-020-17978-9.
Savickas V, Stewart AJ, Rees-Roberts M, Short V, Bhamra SK, Corlett SA, Mathie A, Veale EL (2020). Opportunistic screening for atrial fibrillation by clinical pharmacists in UK general practice during the influenza vaccination season: a cross-sectional feasibility study. PLOS Medicine 17: e1003197. DOI: 10.1371/journal.pmed.1003197.
Savickas V, Veale EL, Bhamra SK, Stewart AJ, Mathie A, Corlett S (2020). Pharmacists detecting atrial fibrillation in general practice: a qualitative focus group study. Brit J Gen Pract Open 4 (3): bjgpopen20X101042.
Cunningham KP, MacIntyre DE, Mathie A, Veale EL (2020). Effects of the ventilator stimulant, doxapram, on human TASK-3 (KCNK9, K2P9.1) and TASK-1 (KCNK3, K2P3.1) channels. Acta Physiologica 228: e13361.
Wright PD, McCoull D, Walsh Y, Large JM, Hadrys BW, Gaurilcikaite E, Byrom L, Veale EL, Jerman J, Mathie A (2019). Pranlukast is a novel small molecule activator of the two-pore domain potassium channel TREK2. Biochemical and Biophysical Research Communications 520: 35-40.
Al-Moubarak E, Veale EL, Mathie A (2019). Pharmacologically reversible, loss of function mutations in the inner pore helices of TREK-1 K2P channels. Scientific Reports 9: 12394.
Cunningham KP, Holden RG, Escribano-Subias P, Cogolludo A, Veale EL, Mathie A (2019). Characterisation and regulation of wild type and mutant TASK-1 two pore domain potassium channels indicated in pulmonary arterial hypertension. J Physiol 597: 1087-1101.
Alexander SPH, Kelly E, Mathie A, Peters JA, Veale EL and CGtP collaborators (2019). The Concise Guide to Pharmacology 2019/20: Br J Pharmacol 176: S1-S493.