2014 Manuscript Awards

Joshua Spin, MD

Philip S. Tsao Lab
Ronald L. Dalman Lab

"miR-24 limits aortic vascular inflammation and murine abdominal aneurysm development" in Nature Communications

This manuscript represents a significant advance in our understanding of abdominal aortic aneurysm (AAA) biology, revealing key pathophysiologic roles and translational potential for microRNA-24 and its target, the novel cytokine CHI3L1. These findings suggest new avenues in the monitoring and treatment of a common and potentially lethal disease.

Pei Han, PhD

Thomas Quertermous Lab 
Ching-Pin Chang Lab

"A long noncoding RNA protects the heart from pathological hypertrophy" in Nature Letters

In the paper, we identified the first long noncoding RNA (lncRNA), Myheart, that can protect the heart from hypertrophy and heart failure. This lncRNA is specifically localized to the nuclei of cardiomyocytes and abundant in adult hearts. We also found Myheart inhibits the function of Brg1, a pro-hypertrophy chromatin-remodeling factor, by directly binding to the helicase core of Brg1. Our studies thus identify a cardioprotective lncRNA, and establish a new paradigm of lncRNA-chromatin interaction, which may also inspire new therapies for cardiovascular diseases.

Antje Ebert, PhD

Joseph C. Wu Lab 

"Characterization of the molecular mechanisms underlying increased ischemic damage in the aldehyde dehydrogenase 2 genetic polymorphism using a human induced pluripotent stem cell model system" in Science Translational Medicine

Nearly 8% of the human population carries an inactivating point mutation in the gene that encodes the cardioprotective enzyme aldehyde dehydrogenase 2 (ALDH2). Our results reveal a new function for the metabolic enzyme ALDH2 in modulation of cell survival decisions. Insight into the molecular mechanisms that mediate ALDH2*2-related increased ischemic damage is important for the development of specific diagnostic methods and improved risk management of CAD (coronary artery disease) and may lead to patient-specific cardiac therapies.

Arun Sharma

Joseph C. Wu Lab 
Sean Wu Lab

"Human induced pluripotent stem cell-derived cardiomyocytes as an in vitro model for coxsackievirus b3-induced myocarditis and antiviral drug screening platform" featured on the cover of Circulation Research

Viral myocarditis is a life-threatening cardiac disease that arises when the heart is infected by a virus such as CVB3. However, it is difficult to obtain human heart tissues with which to study the mechanisms of this disease because cardiac biopsies are invasive and expensive. Recent advances have allowed for the mass production of human heart cells from a patient’s own skin or blood samples. Using this hiPSC-CM technology, we were able to study the mechanisms of CVB3 infection on human cardiomyocytes. We found that hiPSC-CMs express the coxsackievirus receptor needed to internalize CVB3, and hiPSC-CMs are highly susceptible to CVB3 infection because the virus is able to proliferate rapidly and destroy the cells in a matter of hours. The CVB3/hiPSC-CM system that we established here could serve as a platform for discovering novel antiviral compounds that can effectively treat patients suffering from viral myocarditis.