Research

Light, circadian biology, and cardioprotection

Two decades of work tracing how light and the body's internal clock shape recovery from cardiac and lung injury.

The core pathway

From light exposure to cardioprotection

A simplified view of the light–Per2–hypoxia pathway central to Dr. Eckle's cardioprotection research, mapped against the 24-hour circadian cycle.

Landmark study

The Adora2b–Per2–HIF-1α discovery

This 2012 study identified the circadian protein Per2 as the missing link between adenosine receptor signaling and the heart's ability to switch to oxygen-efficient glycolysis during ischemia — and showed that exposing mice to intense light could stabilize cardiac Per2 and reduce infarct size. It remains Dr. Eckle's most-cited paper and the foundation for his light-therapy research program.

Original diagram of adenosine activating Adora2b to induce Per2 via cAMP/pCREB and cullin-1 deneddylation, with light exposure also stabilizing Per2, driving a PER2-HIF-1alpha complex that increases glycolysis and oxygen efficiency during myocardial ischemia — Original illustration of the mechanism reported in Eckle T, Hartmann K, Bonney S, et al. Adora2b-elicited Per2 stabilization promotes a HIF-dependent metabolic switch crucial for myocardial adaptation to ischemia. *Nature Medicine*, 2012.

Focus areas

Areas of research interest

Chronotherapy

Timing drug administration to the body's circadian clock to improve outcomes.

Cardioprotection

Intense light as a novel strategy to treat myocardial injury after non-cardiac surgery.

Critical illness

Light-based treatment strategies for delirium, substance use disorder, and sepsis.

Molecular biology

The circadian protein Period 2 (Per2) in ischemia and reperfusion injury.

Signaling

Adenosine A2B receptor signaling during ischemia, reperfusion, and acute lung injury.

Featured study

Endothelial metabolic reprogramming

Intense light increases the circadian amplitude of the clock protein PER2, which preconditions the heart by reprogramming the endothelium through adenosine and HIF1A signaling — strengthening the endothelial barrier and improving mitochondrial respiration before an ischemic event.

Original diagram: light increases PER2 amplitude in endothelial cells, driving HIF1A-dependent transcriptional reprogramming that strengthens the endothelial barrier and mitochondrial respiration before ischemia — Original illustration of the mechanism reported in Oyama Y, Bartman CM, Bonney S, et al. "Intense Light-Mediated Circadian Cardioprotection via Transcriptional Reprogramming of the Endothelium." *Cell Reports* 28, 1471–1484, August 6, 2019.

From the lab

Circadian ANGPTL4 in cardiovascular disease

Original figures from Dr. Eckle's Forum article in Trends in Molecular Medicine, outlining how circadian ANGPTL4 signaling protects the heart and vasculature.

Original diagram showing feeding, light exposure, and hypoxia converging on a PER2-HIF1A axis to upregulate ANGPTL4, which acts on cardiomyocytes, endothelial cells, and mesenchymal cells to produce cardioprotection — Original illustration summarizing the mechanism reported in Shuff S, Oyama Y, Walker L, Eckle T. Circadian Angiopoietin-like-4 as novel therapy in cardiovascular disease. *Trends in Molecular Medicine*, 2021.

From: Shuff S, Oyama Y, Walker L, Eckle T. Circadian Angiopoietin-like-4 as novel therapy in cardiovascular disease. Trends in Molecular Medicine, 2021.