Massachusetts Institute of Technology

Sejal K Vyas

Paul Chang

Phillip A Sharp

Anthony Leung

The invention provides methods for treating or decreasing the likelihood of developing a stress-granule related disorder and/or cancer by administering one or more poly-ADP-ribose polymerase (PARP) inhibitors, one or more PARP activators, one or more poly-ADP-ribose glycosylase (PARG) activators, and/or one or more poly-ADP-ribose glycohydrolase ARH3 activators. The invention also provides corresponding methods of decreasing stress granule formation and/or proliferation in a cell or a population of cells. The invention further provides methods of increasing the number of stress granules and proliferation in a cell or a population of cells by administering one or more PARP activators, one or more PARP inhibitors, one or more PARG inhibitors, and/or one or more ARH3 inhibitors. The invention also provides methods for screening for agents for treating or decreasing the likelihood of developing a stress granule-related disorder or cancer, and methods for determining the propensity for developing a stress granule-related disorder or cancer, as well as compositions and kits containing one or more PARP inhibitors, one or more PARP activators, one or more PARG activators, and one or more ARH3 activators.

Compositions and methods for treating cancer and modulating stress granule formation

The invention provides nucleic acids encoding PARP fusion proteins, PARP fusion proteins, antibodies that bind to one or more of these PARP fusion proteins, and transgenic cells expressing one or more PARP fusion proteins. The invention also provides methods for identifying an agent as a specific PARP inhibitor or activator requiring contacting one or more PARP fusion proteins with a labeled nicotinamide adenine dinucleotide substrate and the agent and measuring the amount of labeled of ADP-ribose covalently attached to the one or more PARP fusion proteins. The invention also provides methods for identifying an agent that specifically binds to one or more PARP fusion proteins and methods for quantitating the level of one or more PARP proteins in a sample.

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Somerville, MA, United States of America

Sejal K Vyas