Li Group

Modelling neurocardiac interactions in health and disease using Human induced pluripotent stem cells

The heart does not function in isolation, every beat is influenced by a sophisticated dialogue with the nervous system. Disruption of this neurocardiac communication underlies a spectrum of cardiac diseases, from inherited arrhythmias to stress-induced cardiomyopathy. Yet our understanding of these interactions at the cellular and molecular level in humans has been limited by the challenges of studying living human cardiac and neural tissues together.

Human induced pluripotent stem cell (hiPSC) technology has transformed our ability to model human disease. We can now generate both cardiac myocytes and sympathetic neurons from individual patients, creating unprecedented opportunities to study neurocardiac interactions in human cellular systems. We leverage these technologies to develop advanced model systems, from 2D co-cultures to 3D cardiac-neural organoids that robustly recapitulate key physiological responses. Working closely with the Paterson Group on neurocardiac control mechanisms, we employ optical mapping for visualizing calcium dynamics and action potentials, multielectrode array (MEA) recordings for electrophysiology, FRET-based biosensors for real-time signalling dynamics, and advanced imaging to probe how the nervous system modulates cardiac function in health and disease.

Our research spans multiple cardiovascular conditions where neurocardiac interactions play critical roles. The Li Group focuses on inherited arrhythmia syndromes including catecholaminergic polymorphic ventricular tachycardia (CPVT) and long QT syndrome, investigating how mutations affect both cardiac cells and sympathetic neurons. We are establishing hiPSC models of cardiac pathological remodelling, including hypertrophy and diabetic cardiomyopathy to understand how metabolic and mechanical stress alter neurocardiac coupling. In an exciting new direction, we are developing the first human cellular models of depression-induced cardiovascular dysfunction using hiPSCs from patients with major depressive disorder (MDD). A key emerging theme across our work is understanding how the immune system, particularly inflammatory cytokines, modulates neurocardiac interactions in arrhythmias, cardiac remodelling, and psychiatric-cardiovascular comorbidity. We are also investigating novel therapeutic approaches including gene transfer strategies to modulate cardiac innervation and prevent arrhythmias.

Our research addresses four key questions:

1. How do disease-causing mutations in inherited arrhythmia syndromes affect both cardiac myocytes and sympathetic neurons?

2. Can we develop human cellular models that recapitulate neurocardiac dysfunction in cardiac remodelling and psychiatric disease?

3. What are the cellular and molecular mechanisms, including immune-mediated pathways, underlying neurocardiac crosstalk in disease states?

4. Can we develop new therapeutic interventions, including gene transfer approaches, to restore normal neurocardiac function and prevent arrhythmias?

FUNDERS

Our team

Dan Li

Associate Professor
Neda Mohammadi

Postdoctoral Research Scientist
Kazuki Osuka

DPhil Student
Ji Qu

DPhil Student
Shunan Zhang

Visiting student
Nathaniel Merrell

FHS Student
Adam Trevett

FHS Student

Latest news

Associate Professor Dan Li awarded a British Heart Foundation Project Grant

15 January 2026

Two new DPAG Associate Professors

19 May 2023

Congratulations are in order to Associate Professor Nicol Harper and Associate Professor Dan Li.

HCQ with antibiotics to treat COVID-19 could be dangerous for the heart

26 May 2020

DPAG researchers have collaborated on an international study that demonstrates a detailed mechanistic understanding of how the anti-malaria drug, Hydroxychloroquine, combined with antibiotics, can cause adverse cardiac side-effects in COVID-19 patients. This gives weight to US Federal advice against using this combined treatment.

More news