Biography
Prof. Sung-Liang Yu
Prof. Sung-Liang Yu
Clinical Laboratory Sciences and Medical Biotechnology, Natl. Taiwan University, China
Title: Transcriptional and epigenetic regulation involved in Enterovirus 71-induced pathogenesis
Abstract: 

Non-coding RNAs including microRNA and L is the largest family of gene regulators which are involved in more than one-third of cellular processes including interaction between pathogen and host.

Enterovirus 71 (EV71) has become a newly emerging life-threatening pathogen, particularly in the Asia-Pacific region. EV71 can infect humans through fecal-oral route and spread to the central nervous system (CNS). However, there is no effective therapy for EV71 infection. Viruses rely on the host translation machinery to complete their life cycles. We found that miR-141 induced by enterovirus infection targets the cap-dependent translation initiation factor, eIF4E, for shutoff of host protein synthesis. Knockdown of miR-141 reduces viral propagation and silencing of eIF4E can completely reverse the inhibitory effect of the miR-141 antagomiR on viral propagation. EV71 also fails to induce type I interferon response efficiently although this response, elicited upon virus infection, is critical to establishing host antiviral innate immunity. We found EV71 infection upregulates miR-146a, which targets IRAK1 and TRAF6 involved in TLR signalling and type I interferon production. Knocking out miR-146a or neutralizing virus-induced miR-146a by specific antagomiR restores expressions of IRAK1 and TRAF6, augments IFNβ production, inhibits viral propagation, and improves survival in the mouse model. In addition, our study showed EV71 infection upregulates miR-146a but downregulates miR-370 expression. Induction of miR-146a suppresses SOS1 expression and further triggers apoptosis of virus-infected cells. Simultaneously, virus infection-downregulated miR-370 increases GADD45β expression and causes virus-infected cells apoptosis. Finally, we provide a new molecular mechanism underlying pathogen-host interaction wherein host cells govern isoform switching of an interferon-associated molecule in EV71 infection leading to alterations in IFN productions by NGS RNA sequencing. This finding highlights a new gene regulation mechanism in pathogen-host interaction and provides a potential strategy for establishing host first-line defense against pathogens.

Biography: 

Education:

1986 - 1990 B.S., Dep. Clinical laboratory sciences and Medical Biotechnology, Natl. Taiwan University

1990 - 1992 M.S., Dep. Clinical laboratory sciences and Medical Biotechnology, Natl. Taiwan University

1992 - 1999 Ph.D.; Ins. Microbiology and Immunology, Natl. Yang-Ming University

1999 - 2007 Postdoc, Nat. Taiwan University Medical College

Positions and Research Experience:

2007 - 2010 Assist. Prof.; Dep. Clinical laboratory sciences and Medical Biotechnology, NTU

2010 - 2014 Assoc. Prof.; Dep. Clinical laboratory sciences and Medical Biotechnology, NTU

2014 - Current Prof.;

Dep. Clinical laboratory sciences and Medical Biotechnology, NTU;

Dep. Pathology, NTU;

Ins. Medical Device and Imaging, NTU;

Grad. Ins. Clinical Medicine, NTU;

Centers for Genomics and Precision Medicine, NTU;

ISO15189-certificated Pharmacogenomics Laboratory, NTU.