Chemical Proteomics revealed Poly(ADP-ribose) as a Potent for Biomolecular Condensates
- Wednesday 1 June 2022
2333 CC Leiden
We are pleased to announce the visit of Dr. Anthony Leung for a lecture in the LIC. Dr. Anthony K. L. Leung is an expert in the area of gene regulation—specifically RNA, ADP-ribosylation and proteomics and completed his undergraduate at the University of Oxford, followed by a Ph.D. from the University of Dundee under the mentorship of Dr. Angus I. Lamond. After a successful postdoc under the Nobel Laureate Dr. Phillip A. Sharp and Dr. Paul Chang at MIT, he started his lab at Johns Hopkins University in 2011 and was promoted to Associate Professor in 2017.
His research specializes in the field of RNA biology and stress, leading to his discovery of ADP-ribosylation in the cytoplasm as well as the role of macrodomain in viral replication and virulence. Dr. Leung has been recognized with Top 5 Agilent Early Career Professor (2013), the Inaugural Johns Hopkins Catalyst Award (2015), Research Scholar Award from the American Cancer Society (2016), Top 10 Finalist for the American Society of Cell Biology–Gibco Emerging Leader Prize (2016), and the Shikani/El-Hibri Prize for Discovery & Innovation (2019).
In short, a lecture that will be of interest to the wide chemical, chemical biology and pharmaceutical communities within the faculty. If you would like to meet Dr Leung before or after his lecture, then please contact Dmitri Filippov
Poly(ADP-ribose) (PAR) is an RNA-like protein modification that is critical for DNA damage, stress responses, RNA metabolism and cell cycle. Four PAR synthesis inhibitors have already been approved for the treatment of breast, ovarian, and prostate cancers. Despite the clinical significance of PAR, a molecular understanding of its function, including its binding partners, remains incomplete. We recently synthesized a PAR photoaffinity probe that captures and isolates endogenous PAR binders (Dasovich et al., JACS 2021). Our investigation produces the first census of PAR-binding proteins and reveals that PAR-binding is critical for the formation of biomolecular condensates.
We further analyzed one of the top candidates, FUS—a key disease protein for frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Notably, PAR is elevated in patients with neurodegenerative disorders, which are characterized with the aggregation of key disease proteins. We recently discovered that even 1:1000 substoichiometric amount of PAR is sufficient to induce the condensation of the RNA-binding protein FUS (Rhine, Dasovich, Yoniles et al., Mol Cell 2022). These data indicate that PAR is a potent inducer of protein condensation. I will present our latest work on dissecting the mechanism and regulation of these condensate formation and discuss their associated therapeutic opportunities.