By Professor Ming Lei
Ming Lei is Professor of Physiology and Pharmacology in the Department of Pharmacology at the University of Oxford. His research focuses on the electrical activity of the heart and how its disruption leads to cardiac rhythm disorders. He has made major contributions to understanding how ion channels and signalling pathways regulate the cardiac conduction system and has developed new therapeutic strategies for hypertrophic and arrhythmic heart disease. His group recently discovered a previously unknown population of catecholaminergic heart muscle cells, challenging established views of cardiac function, and developed a novel approach for discovering kinase activators. He also led the modernisation of antiarrhythmic drug classification, replacing the longstanding Vaughan Williams system; this framework was adopted internationally in the 2025 European Heart Rhythm Association Clinical Consensus. Professor Lei has published more than 180 peer-reviewed papers in leading journals, including Cell, Nature Communications, Circulation, and Circulation Research, and received the Physiological Society’s 2026 Mabel FitzGerald Prize.
Ming Lei is the 2026 winner of The Mabel Fitzgerald Prize Lecture for Diversity in Physiology. We spoke to Ming as part of our 150 Voices of Physiology series.
It is a privilege to write this perspective as I prepare for the Mabel Fitzgerald Prize Lecture. Throughout my scientific career, I have been fascinated by one fundamental question: how does the heart generate and maintain its own rhythm? This seemingly simple question has led me from cardiac pacemaker cells to ion channels, intracellular signalling, heart–brain communication and, most recently, the discovery of neuroendocrine cardiomyocytes. Looking back, I realise that every stage of this journey has reinforced a lesson that physiology advances by asking fundamental mechanistic questions, and by embracing diverse ways of thinking.
Looking back, I can identify the paper that changed my scientific life. As a graduate student studying cardiovascular medicine in China, I was investigating cardiac pacemaking failure in sick sinus syndrome. At that time, the problem seemed largely clinical. Everything changed when I read Brown, DiFrancesco and Noble’s landmark paper published in Nature in 1979 (Nature 280, 235–236 (1979), How does adrenaline accelerate the heart? Their discovery of the “funny current” provided, for the first time, a mechanistic explanation for cardiac rhythm. Suddenly, what had appeared to be a clinical observation became a fascinating physiological puzzle. That paper convinced me that understanding heart disease required understanding physiology.
That paper ultimately led me to Oxford in 1994, where I had the privilege of undertaking my D.Phil. under Dr Hilary Brown and Professor Denis Noble. They taught me much more than experimental techniques. They demonstrated how rigorous physiological thinking could transform difficult biological problems into solvable scientific questions. More than thirty years later, I remain in close scientific contact with both Hilary and Professor Dario DiFrancesco, whose influence continues to shape my approach to science.
My early independent work focused on understanding how voltage-gated sodium channels contribute to the initiation and propagation of cardiac rhythm. We demonstrated that Nav1.1 and Nav1.5 play critical roles in sinus node pacemaking and conduction, findings that helped redefine prevailing concepts of cardiac pacemaker physiology and linked molecular defects directly to sinus node disease.(Having published a series of papers in The Journal of Physiology, Circulation Research and Cardiovascular Research).
Together with my colaborators, I uncovered the key role of the multifunctional p21 activated kinase type 1, PAK1, as a central signalling hub regulating excitation and homeostasis in cardiomyocytes. This work established PAK1 as a novel therapeutic target and has contributed to the development of a new class of therapeutic agents for hypertrophic heart disease (This was though a series of papers published in Circulation Research, Circulation Journal, and includes a recent paper published in Cell).
Our discovery of Dbh⁺ catecholaminergic cardiomyocytes likely prompted a paradigm shift in our understanding of cardiomyocyte function (Published in Nature Communications 2023).
I led the comprehensive modernisation of antiarrhythmic drug (AAD) classification, replacing the long-standing Vaughan Williams system. The 2018 Oxford Classification（Published in Circulation 2018) has gained international recognition and has been adopted in the European Heart Rhythm Association’s Clinical Consensus (published in Europace, 2025), significantly influencing antiarrhythmic drug practice worldwide.
Almost every major discovery I have made fits into the following narrative:
• Nav1.1/Nav1.5 → how the heartbeat is initiated and propagated.
• PAK1 → how cardiomyocytes maintain homeostasis.
• Oxford Classification → translating physiological understanding into better therapy.
• Dbh⁺ cardiomyocytes → the heart communicating with the brain.
• Diversity → different perspectives working together, just as different cell types work together.
Each of these milestones represents not only scientific progress, but also the dedication of talented students and collaborators who worked alongside me.
My own journey—from medical training in China to an academic career in Oxford—has reinforced another important lesson. Scientific progress benefits from diversity in every sense: diversity of culture, education, experience and perspective. Different backgrounds encourage different questions, and different questions often lead to the most important discoveries.
Looking back over more than three decades in physiology, I remain as excited by unanswered questions as I was when I first encountered the “funny current.” Science is rarely straightforward. It demands patience, persistence and collaboration. Yet it also offers the extraordinary privilege of discovering something entirely new about how life works. That privilege continues to inspire me every day, and it is one I hope to pass on to the next generation of physiologists.