My research program focuses on understanding the relationship between microRNAs and stress in cancers, using biochemical, cellular imaging and genomics approaches. MicroRNA is a class of non-coding RNAs that regulate at least two-thirds of human protein-coding genome. Recently, we discovered that microRNA activity is regulated by poly(ADP-ribose), a "druggable" protein modification that is essential in multicellular organisms. Dysregulation in synthesis of poly(ADP-ribose) results in human diseases including cancers. My research program is to characterize how this protein modification regulates microRNA activities. Through the funding of the Idea Award from the Department of Defense Breast Cancer Research Program, my laboratory recently developed a novel non-biased approach to identify ADP-ribosylation sites from cells—a method that removes a major technical barrier of the field to understand the function and mechanism of ADP-ribosylation. Notably, inhibitors against poly(ADP-ribose) polymerase are recently approved by Food and Drug Administration to treat ovarian cancers. Our goal is to use this novel technique to examine the role of poly(ADP-ribose) in cancers and understand how these diseases can be treated by inhibitors against poly(ADP-ribose) metabolism.
McPherson RL, Abraham R, Sreekumar E, Ong SE, Cheng SJ, Baxter VK, Kistemaker HA, Filippov DV, Griffin DE, Leung AK. ADP-ribosylhydrolase activity of Chikungunya virus macrodomain is critical for virus replication and virulence. PNAS 2017 PMID: 28143925
Vivelo CA, Wat R, Agrawal C, Tee HY, Leung AK. ADPriboDB: The database of ADP-ribosylated proteins. Nucleic Acids Res. 2016 PMID: 27507885.
Daniels CM, Ong SE, Leung AK. The Promise of Proteomics for the Study of ADP-Ribosylation. Mol Cell. 2015 PMID: 26091340.
Daniels CM, Ong SE, Leung AK. Phosphoproteomic approach to characterize protein mono- and poly(ADP-ribosyl)ation sites from cells. J Proteome Res. 2014 PMID: 24920161.
Leung AK, Vyas S, Rood JE, Bhutkar A, Sharp PA, Chang P. Poly(ADP-ribose) regulates stress responses and microRNA activity in the cytoplasm. Mol Cell. 2011 PMID: 21596313.