Current Projects
Transcriptional Regulation of Cardiac Pathological Remodeling
Cardiac gene expression governs the health status of the heart. Gene expression under different conditions, including both physiological (such as circadian rhythm) and pathological (such as heart failure and MI) conditions are highly regulated. We found a core clock component REV-ERBα regulates cardiac pathological remodeling in various disease models. We are now focusing on studying the molecular mechanism of circadian gene regulation in the heart, as well as developing novel therapeutic opportunities in treating heart failure.
Circadian Regulation of Cardiac Ischemia Reperfusion Injury
The circadian regulation occurs at multiple layers. We identified the first “slave clock” in the heart, KLF15. We discovered that KLF15 coordinates cardiac catabolism and ROS clearance and regulates the circadian susceptibility of ischemia reperfusion injury by controlling cardiac NAD+. We are now studying the molecular mechanism of NAD+ regulation in the heart.
Circadian Eegulation of Post Myocardial Infarction Remodeling
We discovered the first circadian lncRNA in the heart, which regulates post myocardial infarction remodeling through direct interaction with splicing factors and affect alternative splicing. We are now focusing solving the RNA structure function relationship and investigating its molecular mechanism through interaction with protein partners.
Using the iPSC Differentiated Cardiomyocytes to Understand Inherited Cardiac Disease
The iPSC-CM provide a unique tool to study genetic cardiac diseases. We use both 2D and 3D culture combined with genome editing to create disease models. One current focus is TANGO2 disease, which may present with cardiac crises with arrhythmia and heart failure. By recreating these crises in the dish, we will develop a deep understanding of the nature of the crises, their predisposing factors and test treatment strategies.
Using the iPSC Differentiated Cardiomyocytes for Variant Interpretation
Current capacity of clinical sequencing has yielded and continued to yield variants we do not know how to interpret. Using the iPSC-CM platform, we are working on developing high throughput strategies to assign functional consequence of large number of variants.
