PAR condensates
How do cells control biomolecular condensate formation, disassembly and composition?
Poly(ADP-ribose) in Stress Granules
We discovered that poly(ADP-ribose), or PAR, is critical for the formation of stress granules—a class of biomolecular condensates enriched with mRNA translation factors and implicated in viral infection, cancer chemotherapeutic resistance and neurodegeneration. We are investigating the regulatory mechanisms behind these disease states, with the goal of turning our actionable targets into therapeutic applications.
Leung AK, Vyas S, Rood JE, Bhutkar A, Sharp PA, Chang P. Poly(ADP-ribose) regulates stress responses and microRNA activity in the cytoplasm. Mol Cell. 2011 May 20;42(4):489-99. [Abstract/PDF]
PAR code hypothesis to build
Biomolecular Condensates
PAR can be conjugated to different amino acids with varying numbers of ADP-ribose, and the ADP-ribose can be connected with two possible configurations, resulting in the formation of linear or branched chains. Analogous to the ubiquitin code, the different sites, lengths, and structures may comprise a PAR code that directs the biological outcome.
Leung AK. Poly(ADP-ribose): an organizer of cellular architecture. J Cell Biol. 2014 Jun 9;205(5):613-9. [Abstract/PDF]
Leung AKL. Poly(ADP-ribose): A Dynamic Trigger for Biomolecular Condensate Formation. Trends Cell Biol. 2020 May;30(5):370-383. [Abstract/PDF]
Biomolecular condensates compartmentalize macromolecules to regulate diverse cellular processes, including RNA metabolism, DNA repair and neurotransmission. In cells, protein condensation is facilitated by their interactions with multivalent macromolecules such as nucleic acids. Our research focuses on how biomolecular condensates are regulated by an understudied, but therapeutically targetable, nucleic acid called poly(ADP-ribose).