01 — BIOLOGY
Define the substrate
We study inflammatory signaling, NLRP3 inflammasome activation, fibroblast biology and structural remodeling that create vulnerability to AF.
Our Research
Understanding arrhythmia biology to build new therapies.
Cardiac rhythm disorders are commonly treated as electrical
diseases. Our laboratory studies the biology underneath the
electrical phenotype — inflammation, innate immune signaling,
fibrosis and tissue remodeling — and uses those insights to
develop new therapeutic strategies.
Flagship Program
Extracellular vesicle therapy for atrial fibrillation
Atrial fibrillation is defined by abnormal electrical activity, but the atrium in which AF develops is also biologically abnormal. Inflammation, fibroblast activation and progressive fibrosis alter conduction and create a substrate capable of initiating and sustaining the arrhythmia.
Drugs and catheter ablation can control rhythm or eliminate electrical triggers, but they do not directly reverse this fibro-inflammatory substrate. Our laboratory is testing whether human heart-derived extracellular vesicles can change the biology of the diseased atrium itself.
Central Research Question
Can we biologically modify the atrial substrate so that atrial
fibrillation is less able to start, persist or recur?
02 — THERAPY
Intervene biologically
We use heart-derived extracellular vesicles as an acellular biologic designed to suppress inflammatory and profibrotic signaling within diseased atrial tissue.
03 — TRANSLATION
Build toward patients
Mechanistic experiments are integrated with human atrial models, rodent and large-animal studies, delivery optimization and clinically relevant EV manufacturing.
Mechanism
A substrate-directed model of atrial fibrillation
Our working model connects innate immune activation to structural
remodeling and electrical vulnerability. Heart-derived extracellular
vesicles intervene upstream in this pathway rather than acting as
conventional antiarrhythmic drugs.
Translational Evidence
Building the evidence from discovery toward patients
The program integrates mechanistic discovery with human atrial biology, preclinical efficacy, clinically relevant manufacturing and the requirements needed to move extracellular vesicle therapy toward first-in-human testing.
2023 · JCI Insight
Proof of concept
Direct atrial delivery of human heart-derived EVs prevented the increase in AF vulnerability caused by sterile pericarditis and markedly reduced atrial inflammation, fibrosis and remodeling in a rodent model of postoperative AF.
Read the paper →
2024 · Theranostics
Dose response and mechanism
Increasing EV dose produced progressive reductions in inflammatory and fibrotic remodeling. Mechanistic studies identified suppression of the NLRP3 inflammasome in atrial fibroblasts and macrophages as a key component of the response.
Read the paper →
2026 · Theranostics
Human atrial biology
Human atrial EVs were tested in patient-specific iPSC-derived atrial fibroblast models and primary human atrial fibroblasts, demonstrating suppression of NLRP3-associated inflammatory and profibrotic signaling.
Read the paper →
2026 · JACC: Basic to Translational Science
Large-animal translation
Targeted intra-atrial delivery of GMP-grade human cardiac EVs was feasible and well tolerated in pigs, prevented spontaneous postoperative AF, reduced inducible AF and attenuated atrial inflammatory and fibrotic remodeling.
Read the paper →Current Questions
Defining how EVs modify the atrial substrate
Our current work focuses on the cellular and molecular basis of EV activity, the interaction between EVs and diseased atrial tissue, and the extent to which substrate-directed therapy can apply across different forms of atrial disease.
01
How do EVs interact with diseased atrial tissue?
We are defining the cellular and tissue determinants that
influence EV uptake, localization and biological activity
within the diseased atrium.
02
Which cells mediate therapeutic effects?
We are identifying the atrial cell populations responsible
for EV uptake and determining how their responses contribute
to changes in the surrounding tissue.
03
What makes the therapy work?
We are defining EV cargo and the inflammatory and fibrotic
pathways responsible for modification of the arrhythmogenic
atrial substrate.
04
How broadly does the biology apply?
We are testing whether substrate-directed EV therapy can modify
atrial remodeling across distinct disease states and stages
of atrial fibrillation.
Disease Modeling
Cardiac sarcoidosis
Cardiac sarcoidosis can produce conduction disease, ventricular arrhythmias, myocardial fibrosis and heart failure, yet progress in understanding its biology has been limited by the lack of experimental models that reproduce the cardiac phenotype.
Recreating granulomatous disease
Our laboratory developed an experimental model in which intramyocardial carbon nanotubes generate persistent histiocytic lesions resembling the granulomas seen in cardiac sarcoidosis. These lesions are associated with clinically relevant abnormalities of cardiac conduction.
Modeling progressive myocardial disease
Priming the heart with transverse aortic constriction before intramyocardial carbon nanotube injection produces a more advanced phenotype, with increased myocardial fibrosis, impaired ventricular function and persistent conduction abnormalities.
Selected Publications
Research supporting these programs
Targeted Intra-Atrial Delivery of GMP-Grade Human
Extracellular Vesicles Prevents Inflammation-Driven
Postoperative Atrial Fibrillation in Pigs
Paper →
Human atrial extracellular vesicles suppress NLRP3 inflammasome
activation and profibrotic signaling in a patient-specific
model of postoperative atrial fibrillation
Paper →
Inactivation of the NLRP3 inflammasome mediates
exosome-based prevention of atrial fibrillation
Paper →
Development of a Mouse Cardiac Sarcoidosis Model
Using Carbon Nanotubes
Paper →
Prevention of atrial fibrillation after open-chest surgery
with extracellular vesicle therapy
Paper →
Cardiac Translational Research Laboratory
Mechanism informs translation.
Our research connects fundamental cardiovascular biology with
clinically relevant models and therapeutic development, with the
goal of changing how arrhythmogenic disease is understood and treated.
