My research program focuses on how gene regulation impacts diseases states including cancer, neurodegeneration and virus infection. Recent research focus includes noncoding RNAs, such as circular RNAs and microRNAs, and a druggable protein modification called poly(ADP-ribose). Poly(ADP-ribose) polymerase (PARP) inhibitors are currently approved by FDA to treat multiple cancers. Though therapeutically important, this modification is understudied partly due to a woeful lack of tools. My team invents tools to investigate this protein modification, discovering its roles in various RNA processes, RNA virus infection, and the formation of membrane-less organelles. To dissect the underlying mechanisms, our team also use a range of multi-disciplinary techniques from chemical probe synthesis, single-molecule biophysical measurements and quantitative imaging to informatics, genomics and proteomics approaches. Our team is highly collaborative drawing expertise within the lab, the university and around the world. Our goal is to translate our multi-dimensional scientific findings to therapy and diagnostics.
Ando Y, Elkayam E, McPherson RL, Dasovich M, Cheng SJ, Voorneveld J, Filippov DV, Ong SE, Joshua-Tor L, Leung AKL. ELTA: Enzymatic Labeling of Terminal ADP-Ribose. Mol Cell. 2019 PMID: 30712989
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
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.