Research/Areas of Interest:

The failing heart demonstrates alterations in gene splicing, suggesting an important role for splicing factors (SFs) in heart failure (HF). However, the subset of SFs which contribute to HF remains incompletely defined. The SF hnRNP-L is a multifunctional RNA-binding protein (RBP) with highly conserved expression in skeletal and cardiac muscle. HnRNP-L is required for normal  skeletal myoblast development and function, but its role in the heart has not been investigated. Heart-specific downregulation of hnRNP-L in Drosophila caused shortened lifespan and features reminiscent of HF. To investigate the role of hnRNP-L  in HF, we obtained hnRNP-Lfl/fl mice, to enable cardiac myocyte-restricted hnRNP-L excision. Both hnRNP-Lfl/fl x aMHC-Cre+ and hnRNP-Lfl/fl x aMHC-Cre- mice littermates we will analyzed to first confirm hnRNP-L excision in the right progeny. We will then determine baseline left ventricular function by echocardiography and invasive pressure volume loops. We will measure indices of pathological cardiac remodeling including LV hypertrophy, fibrosis, and fetal gene re-expression. These studies will be the first to determine the role of hnRNP-L in pathological remodeling in vivo. We hypothesize that hnRNP-Lfl/fl Cre+ mice will display reduced LV dysfunction and more severe cardiac remodeling compared with controls. If these hypotheses are confirmed, we will explore diagnostic strategies using hnRNP-L in conditions such as HF with normal LV ejection fraction, and we will explore therapeutic strategies to augment hnRNP-L in HF. 


BS, Marine Pharmaceutical Sciences, China Pharmaceutical University, Nanjing China