Assistant Professor
Research Areas
Premature termination codons
Research Interests
I am interested in the treatment of genetic diseases caused by premature termination codons (PTCs). Currently, two main therapeutic approaches have been intensively investigated to treated PTCs-caused genetic diseases. One treatment uses low molecular weight compounds to induce read through at PTCs in order to generate full-length proteins. Another approach is to inhibit nonsense-mediated mRNA decay (NMD) pathway to increase the abundance of the mRNA harboring PTCs, which serves as the template for protein translation. I am currently exploring the possibility of combining these two approaches as a viable therapeutic strategy to treat a range of genetic diseases caused by PTCs.
In collaboration with the Dr. Bedwell and Keeling labs, we have developed a variety of NanoLuc-luciferase-based mammalian readthrough/NMD reporter cell lines, and those cell lines have been utilized for a high throughputscreen (HTS) to discover new drugs that suppress PTCs and/or inhibit NMD. Several initial hits have been identified. We are currently working intensively on testing and verifying those potential PTC suppression drugs and NMD inhibitors. We will further conduct suppression effect of those newly discovered pharmaceutical compounds in cell based and animal models of two genetic diseases, cystic fibrosis (CF) and mucopolysaccharidosis I-Hurler (MPS I-H) that we developed in previous studies.
Meanwhile, I am also interested in whether those potential readthrough drugs and NMD inhibitors discovered by HTS could also affect normal termination codons(NTCs). Prior research in this area has been largely inconclusive. For PTC suppression therapy to be viable in the clinic, it will be important to test whether readthrough compounds and/or NMD inhibitors identified by HTS do not affect NTCs. I am currently working on developing a new set of luciferase-based reporters to distinguish the effects of readthrough drugs and NMD inhibitors on PTCs and NTCs.
Education
Graduate School
Ph.D., Chiba University School of Medicine, Japan
Postdoctoral Fellowship
University of Alabama at Birmingham
Contact
Office
Bevill Biomedical Research Building
Room 436
845 19th Street South
Birmingham, AL 35294-2170
Phone
(205) 934-3080
Email
dalian@uab.edu