Anthony K. L. Leung
615 N. Wolfe Street
Room E8632
Baltimore, MD 21205
Laboratory of PARP biology in RNA metabolism
Our research program focuses on how gene regulation impacts diseases states, including cancer, neurodegeneration and virus infection. Recent research focus includes a druggable protein modification called poly(ADP-ribose). Poly(ADP-ribose) polymerase (PARP) inhibitors are currently approved by the FDA to treat multiple cancers. Though therapeutically important, this modification is understudied partly due to a woeful lack of tools.
We invent tools to investigate this protein modification, and have discovered its roles in various RNA processes, RNA virus infection, and the formation of RNA granules and other biomolecular condensates. To dissect the underlying mechanisms of poly(ADP-ribose), we 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 from within the lab, the university and around the world. We aim to translate our scientific findings to medicine.
Rhine K, Dasovich M, Yoniles J, Badiee M, Skanchy S, Ganser L, Ge Y, Fare CM, Shorter J, Leung AKL*, Myong S*. Poly(ADP-ribose) Drive Condensation of FUS via a Transient Interaction. (*co-corresponding) Mol Cell 82: 1-17.
Dasovich M, Zhuo J, Goodman JA, Thomas A, McPherson RL, Jayabalan AK, Busa VF, Cheng SJ, Murphy BA, Redinger KR, Alhammad YMO, Fehr AR, Tsukamoto T, Slusher BS, Bosch J, Wei H, Leung AKL. High-Throughput Activity Assay for Screening Inhibitors of the SARS-CoV-2 Mac1 Macrodomain. bioRxiv 2021 Oct 11; ACS Chem Biol. 2021 Dec 14
Dasovich M, Beckett MQ, Bailey S, Ong SE, Greenberg MM, Leung AKL. Identifying Poly(ADP-ribose)-Binding Proteins with Photoaffinity-Based Proteomics. J Am Chem Soc. 2021 Mar 3;143(8):3037-3042.
Jayabalan AK, Adivarahan S, Koppula A, Abraham R, Batish M, Zenklusen D, Griffin DE, Leung AKL. Stress granule formation, disassembly, and composition are regulated by alphavirus ADP-ribosylhydrolase activity. Proc Natl Acad Sci U S A. 2021 Feb 9;118(6):e2021719118.
Leung AKL. Poly(ADP-ribose): A Dynamic Trigger for Biomolecular Condensate Formation. Trends Cell Biol. 2020 May;30(5):370-383. [Abstract/PDF]
Fischer JW, Busa VF, Shao Y, Leung AKL. Structure-Mediated RNA Decay by UPF1 and G3BP1. Mol Cell. 2020 Apr 2;78(1):70-84.e6.
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.