Professor
Biochemistry and Molecular Biology Department, School of Public Health
RESEARCH OVERVIEW
My research program focuses on how gene regulation impacts diseases states including cancer, neurodegeneration and virus infection. Recent research focuses on a druggable protein modification called ADP-ribosylation. Poly(ADP-ribose) polymerase (PARP) inhibitors are currently approved by FDA to treat multiple cancers, while RNA viruses (e.g., coronavirus and alphaviruses) possess a conserved domain that removes ADP-ribosylation, which is critical for viral replication and virulence. We are now actively targeting this domain to develop novel antivirals.
Though therapeutically important, ADP-ribosylation 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 biomolecular condensates. 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.
Cell Biology | Cellular Stress and Cell Signaling | Chemical Biology and Proteomics | Genetics, Genomics and Gene Regulation | Immunology and Infectious Diseases
Selected Publications
Rhine K, Dasovich M, Yoniles J, Badiee M, Skanchy S, Ganser LR, Ge Y, Fare CM, Shorter J, Leung AKL*, Myong S*. Poly(ADP-ribose) drives condensation of FUS via a transient interaction. Molecular Cell, 2022. *Co-corresponding authors
Dasovich M, Beckett MQ, Bailey S, Ong SE, Greenberg MM, Leung AKL. Identifying Poly(ADP-ribose)-Binding Proteins with Photoaffinity-Based Proteomics. Journal of the American Chemical Society, 2021.
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. PNAS, 2021.
Fischer JW, Busa VF, Shao Y, Leung AKL. Structure-Mediated RNA Decay by UPF1 and G3BP1. Molecular Cell, 2020.
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. Molecular Cell, 2019.
Learn More
NCBI Bibliography | Faculty Profile | Lab Website | Facebook | ResearchGate | Google Scholar | LinkedIn | Twitter