Pioneering work on the roles of voltage-gated Na channels in cardiac pacemaking and sinus node dysfunction (J Physiol 2004, 2005, Circ Res 2010)
Determination of the cardiac protective roles of P21-activated kinases and therapy in heart disease conditions (Circ Res 2007, Circulation 2010, Circ A & E 2014)
Modernizing the classification of antiarrhythmic drugs (Circulation, 2018;138, 1879–1896)
Discovery of a novel population of catecholaminergic endocrine cardiomyocytes (Nature Comm 2023)
Our research mainly seeks to unravel the complexities of cardiac electrical function and its signalling regulation both in physiological and pathological conditions. It will lead to a better mechanistic understanding of hypertrophic and arrhythmic disorders, culminating in the development of more effective therapeutic interventions. We employ cutting-edge techniques encompassing genetic manipulation technologies and multi-scale electrophysiological, optogenetic, and molecular approaches.
My group has made fundamental contributions towards identification of the novel roles of a multifunctional enzyme-p21 activated kinase (Pak1) in the heart. We demonstrated that Pak1 is central to the regulation of cardiac excitation and is a critical signalling hub in cardioprotection. We also have established Pak1 as a novel therapeutic target for treating cardiac disease conditions including cardiac arrhythmias.
We are now working on the future treatment of heart diseases using Pak1 as a novel target. Using structure-based rational drug design, we have already developed a series of novel Pak1 activator compounds as starting point compounds for the future drug development for the cardiac conditions.
We recently unveiled a remarkable previously unrecognised population of cardiomyocytes named "Dbh+ Catecholaminergic Cardiomyocytes" (Dbh+ Cate-CMs), paving the way for a potentially groundbreaking advancement in the field of neurocardiology. These cells, which express the enzyme dopamine-beta-hydroxylase (Dbh) and so can synthesise norepinephrine, originate from cardiomyocyte lineage, contribute to the development, maturation, and function of the cardiac conduction system (CCS). More importantly, the findings also suggest a close structural relationship between these cells and sympathetic innervation during the formation of the CCS. The physical co-localization of these cells, primarily within the ventricles, strongly implies a dynamic and vital interaction between Dbh+ Cate-CMs and the autonomic nervous innervation, which is already known to be highly abundant in the CCS.
Our team
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Ming Lei
Professor of Physiology and Pharmacology
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Christopher Beaudoin
Postdoctoral Research Assistant
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Yu He
Postdoctoral Research Assistant in Cardiac Signalling
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Tianyi Sun
BHF Intermediate Postdoctoral Basic Science Research Fellow
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Ines Sousa dos Santos
Research Assistant in Cardiac Signalling
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Lydia Krexi
DPhil Student
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Yue Ren
DPhil Student
BHF Non-clinical PhD Studentship: Electrochemical characterization of catecholaminergic signalling in Dbh+ catecholaminergic cardiomyocytes and its physiological role in murine heart
A three-year PhD studentship, funded by the British Heart Foundation, is available in the cardiac signalling group of Professor Ming Lei.
About the Project
Catecholamines, including dopamine, norepinephrine (NE), and epinephrine (E), are key signalling molecules that function as both neurotransmitters and hormones. These molecules, released by sympathetic nerves and the adrenal medulla, play a crucial role in regulating cardiovascular functions while orchestrating the body’s response to stress. Our recent studies have identified a novel population of cardiomyocytes expressing the Dbh gene that encodes dopamine beta-hydroxylase (termed Dbh+ catecholaminergic cardiomyocytes, Dbh+-CCMs)(1). These cells contribute significantly to the development and maturation of the cardiac conduction system (CCS) in the murine heart. Notably, adult Dbh+-CCMs contain catecholaminergic-like vesicles, suggesting the presence of intrinsic catecholaminergic signalling within these cells. Despite these insights, our understanding of catecholaminergic signalling and its functional role in Dbh+-CCMs remains limited.
This is joint project between Department of Pharmacology at University of Oxford and School of Life Sciences at University of Nottingham..The project aims to characterize catecholaminergic signalling and explore its physiological implications in Dbh+-CCMs through three integrated studies: 1) Developing a robust method to detect catecholamine release in these cells; 2) Conducting electrochemical analysis of vesicle content and catecholamine release in these cells; and 3) Determining the physiological role of catecholaminergic signalling in Dbh+-CCMs in murine heart.
Successful outcome of this study will i) identify the distinct roles of Dbh+-CCMs in cardiac electrophysiology and Ca2+ handling in the heart; ii) lay the basic science foundation for manipulating Dbh+-CCMs populations as a potentially valuable therapeutic strategy for the treatment of cardiac arrhythmias.
This project is multidisciplinary in approach, integrating molecular cardiology, electrochemical sensing and translational physiology. In addition to these fields of study and associated experimental methodologies, the student will acquire skills in a range of topics which include analytical, communication and experimental design that are widely applicable to a future career in. academia, industry or translation medicine.
Requirements:
A Master's degree with Merit and a Bachelor's degree with first-class or upper second-class honors are required for PhD admissions. Prior research experience in cardiac physiology or neuroscience or related topic is critical. If the first language is not English, the candidate should have an IELTS (or equivalent) score of 6.5 or above.
Funding:
The PhD studentship is available for three years subject to satisfactory progress by the student. The award covers tuition fees (at home rate, for non-UK candidate, they need to cover the extra cost of tuition fee between home rate and non-UK rate), stipend (starting from ~£20K annually) and research expense for three years.
How to Apply: make an application for the Oxford University DPhil in Pharmacology programme at: https://www.ox.ac.uk/admissions/graduate/courses/dphil-pharmacology and identify Professor Ming Lei as your preferred supervisor. Deadline for applications: Tuesday 2 December 2025.