Edward G. Lakatta

A novel multicellular model of the adult mouse sinoatrial node retains spontaneous electrical activity and enables live investigation of the S100B-associated cell population

Dissociated adult mouse sinoatrial node cultures stay spontaneously electrically active beyond ten days on MEA arrays and, on compliant hydrogels, permit live tracking of heterogeneous S100B-EGFP-labeled cells.

Cardiac Pacemaker Cells Harness Stochastic Resonance to Ensure Fail-Safe Operation at Low Rates Bordering on Sinus Arrest

This study shows cardiac pacemaker cells use stochastic resonance to maintain rhythm at low heart rates, improving reliability in noisy conditions.

A New Fight-or-Flight Pacemaker Mechanism via Ryanodine Receptor Abundance and Superclustering

This paper uses dSTORM to visualize RyR clusters in rabbit SANCs and develops a model showing superclustering and RyR density changes modulate APCL during βAR stimulation.

Proton tunneling at the ryanodine receptor Ca2+ activation site provides temperature-invariant noise for robust Ca2+-induced Ca2+ release

Sinoatrial Node Impulses Emerge From Incessant, Unique Kinetic Transitions In Disordered Local Calcium Dynamics

The paper analyzes local calcium dynamics in mouse sinoatrial node cells to show how stochastic transitions in heterogeneous calcium oscillations generate rhythmic impulses.

Structure-Function Relationship of the Ryanodine Receptor Cluster Network in Sinoatrial Node Cells

This study examines the structure-function relationship of Ryanodine Receptor (RyR) clusters in sinoatrial node cells, showing how heterogeneities in cluster size and location influence calcium release and action potential firing rates.

Cardiac Specific Overexpression of Adenylyl Cyclase 8 Reprograms the Mouse Sinoatrial Node Transcriptome

This study identifies transcriptomic changes in the sinoatrial node of mice overexpressing AC8, revealing altered pathways and transcription factors linked to cardiac aging and disease.

Reprogramming of cardiac phosphoproteome, proteome and transcriptome confers resilience to chronic adenylyl cyclase-driven stress

The paper integrates phosphoproteomics, proteomics, and transcriptomics to show that reprogramming of cardiac signaling pathways enhances resilience to chronic adenylyl cyclase stress.

Transcriptome of left ventricle and sinoatrial node in young and old C57 mice

The paper compares age-related molecular changes in left ventricle and sinoatrial node cells from young and old C57 mice using transcriptomic analysis to identify age-associated gene expression patterns and regulatory mechanisms.

Metformin attenuates hyperglycaemia-stimulated pro-fibrotic gene expression in vascular adventitial fibroblasts via inhibition of Discoidin Domain Receptor 2

This study shows metformin reduces DDR2-mediated fibrosis in vascular fibroblasts under hyperglycaemia by inhibiting TGF-β1/Smad2/3 signalling.

Functional heterogeneity of cell populations increases robustness of pacemaker function in a numerical model of the sinoatrial node tissue

The paper uses a computational model to show that functional heterogeneity in pacemaker cells enhances the robustness of SAN function by enabling cooperative interactions between firing and dormant cells.

Discoidin Domain Receptor 2 regulates AT1R expression in Angiotensin II-stimulated cardiac fibroblasts via fibronectin-dependent Integrin-β1 signaling

This study identifies DDR2-mediated fibronectin regulation as a key mechanism for Angiotensin II-induced AT1R expression in cardiac fibroblasts through Integrin-β1 signaling.

Discovering patterns of pleiotropy in genome-wide association studies

This paper introduces SAPPHO methods to detect pleiotropy in GWAS by modeling shared patterns of genetic associations, finding 16 additional and 124 novel loci in meta-analysis.

Genome-wide association meta-analysis of PR interval identifies 47 novel loci associated with atrial and atrioventricular electrical activity

This study identifies 47 novel genetic loci associated with PR interval through genome-wide association meta-analysis across multiple populations.