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Anthony K. L. Leung
Anthony K. L. Leung
Biochemistry, Molecular Biology, Bloomberg SPH
Molecular Biology and Genetics
615 N. Wolfe Street
Baltimore, MD 21205
Mechanism of gene regulation at RNA and protein levels.
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; 73(4):845-856.e5.
Leung AKL, McPherson RL, Griffin DE. Macrodomain ADP-ribosylhydrolase and the pathogenesis of infectious diseases. PLoS pathogens. 2018; 14(3):e1006864.
Leung AKL. PARPs. Current biology 2017; 27(23):R1256-R1258. Fischer JW, Leung AK. CircRNAs: a regulator of cellular stress. Critical reviews in biochemistry and molecular biology. 2017; 52(2):220-233.
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. The Promise of Proteomics for the Study of ADP-Ribosylation. Molecular Cell. 2015; 58(6):911-24.
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. Poly(ADP-ribose): an organizer of cellular architecture. The Journal of cell biology. 2014; 205(5):613-9.
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.
Leung AK, Young AG, Bhutkar A, Zheng GX, Bosson AD, Nielsen CB, Sharp PA. Genome-wide identification of Ago2 binding sites from mouse embryonic stem cells with and without mature microRNAs. Nature structural & molecular biology. 2011; 18(2):237-44.
Leung AK, Sharp PA. MicroRNA functions in stress responses. Molecular Cell. 2010; 40(2):205-15.
Leung AK, Calabrese JM, Sharp PA. Quantitative analysis of Argonaute protein reveals microRNA-dependent localization to stress granules. PNAS 2006; 103(48):18125-30.