Research
Jun-ichi Abe, M.D., developed a focused research program during the 15 years since he became an independent researcher. His long-standing interest has always been in signal transduction mechanisms in the cardiovascular system. Recently, Abe’s lab team observed a very unique post-translational modification on ERK5, called ERK5-SUMOylation. This ERK5-SUMOylation happens at the K6 and K22 sites on the N-terminal region of ERK5, and inhibits ERK5 transcriptional activity.
Although the exact mechanism remains unclear, high glucose, reactive oxygen species, and advanced glycation end products (AGEs) can induce ERK5-SUMOylation and inhibit ERK5 transactivation. This ERK5-SUMOylation and subsequent inhibition of ERK5 transactivation is one of the mechanisms to explain diabetes-mediated endothelial inflammation and dysfunction (Circ. Res., Woo, 2008). While in the heart this modification induces PDE3-ICER feedback loop and subsequent apoptosis (Circ. Res., Shishido, 2008). Therefore, this new post-translational modification of ERK5 could be a very important process to regulate both endothelial and cardiac physiology, especially in diabetic conditions.
Not limited to ERK5-SUMOylation, Abe’s group also worked on various interesting post-translational modifications including Bcr-mediated PPARg phosphorylation (Circ. Res., 2009), and MK2-SUMOylation (Blood, 2010). Furthermore, his next study showed that diabetes activates p90RSK, which directly inhibits the transcriptional activity of ERK5, an atheroprotective non-classical MAP kinase. When activated p90RSK associated with ERK5, this association inhibited ERK5 transcriptional activity and up-regulated VCAM-1 expression.
In addition, p90RSK directly phosphorylated ERK5 S496 and reduced eNOS expression. This data showed the importance of the p90RSK-ERK5 module in inflammatory responses in ECs and promotes vascular dysfunction (Circulation, 2013).
Very recently Abe’s group found that disturbed flow induced SUMOylation of p53 and ERK5, leading to ECs apoptosis and inflammation, respectively. Reduced expression of SENP2 increased both p53 and ERK5 SUMOylation, hence increased EC dysfunction and inflammation, and accelerated atherosclerosis formation in vivo. These results indicate for the first time that SENP2 function plays an important role in atherosclerosis formation (Circ. Res., 2013). Dr. Abe made major contributions in analyzing new aspects of signal transduction pathways, especially for SUMOylation, in cardiovascular pathophysiology.
Abe received grants from the National Institute of Health and American Heart Association. He was a Fellow of American Heart Association (FAHA), Dean’s Professor at University of Rochester, Established Investigator of the American Heart Association, and was elected to ATVB Special Recognition Award in Vascular Biology. He has written over 100 scientific papers and book chapters, and is a current member of the Editorial Board of the Journal of American College of Cardiology, Circulation Research, Arteriosclerosis, Thrombosis and Vascular Biology, Journal of Molecular and Cellular Cardiology, Journal of Cardiovascular Translational Research, Clinical Science, and Metabolism.