- Joint Appointment in Molecular Biology and Genetics
- Joint Appointment in Oncology
non-coding RNAs; RNA-binding proteins; post-translational modifications; PARP inhibitors; RNA granules; diagnostics; proteomics
Laboratory of Gene Regulation
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.
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; 114(7):1666-1671.
Vivelo CA, Wat R, Agrawal C, Tee HY, Leung AK. ADPriboDB: The database of ADP-ribosylated proteins. Nucleic acids research. 2017; 45(D1):D204-D209.
Daniels CM, Ong SE, Leung AK. Phosphoproteomic approach to characterize protein mono- and poly(ADP-ribosyl)ation sites from cells. Journal of proteome research. 2014; 13(8):3510-22.
Leung AK, Vyas S, Rood JE, Bhutkar A, Sharp PA, Chang P. Poly(ADP-ribose) regulates stress responses and microRNA activity in the cytoplasm. Molecular Cell. 2011; 42(4):489-99.
Ando Y, Elkayam E, McPherson RL, Dasovich M, Cheng SJ, Voorneveld J, Filippov DV, Ong SE, Joshua-Tor L, Leung AK (2019). ELTA: Enzymatic Labeling of Terminal ADP-ribose. Mol Cell 73:845-856.e5
Biochemistry and Molecular Biology (JHSPH)
Biochemistry, Cellular and Molecular Biology (JHSOM)
Human Genetics Program, Institute of Genetic Medicine (JHSOM)
Chemistry–Biology Interface (JHU)