CSHL 2026 Conference on the PARP Family & ADP-Ribosylation - Cold Spring Harbor Laboratory Conference on The PARP Family and ADP-ribosylation March 25 to 28, 2026 ABSTRACT This proposal seeks support for a scientific meeting on “The PARP Family and ADP-ribosylation,” held at Cold Spring Harbor Laboratory (CSHL) on March 25–28, 2026. ADP-ribosylation is a reversible post- translational modification (PTM) of proteins, RNA, and DNA catalyzed by the enzymes of the PARP family— comprising 17 members in humans. PARPs utilize nicotinamide adenine dinucleotide (NAD⁺) as a substrate to transfer either a single ADP-ribose unit (mono-ADP-ribosylation, or MARylation) or multiple units in a chain (poly-ADP-ribosylation, or PARylation). Like other PTMs, ADP-ribosylation involves writer, eraser, and reader proteins. Initial research focused on the writers PARP1 and PARP2, which generate PAR chains in response to DNA damage, leading to the discovery of the synthetic lethal interaction between PARP1/2 and BRCA1/2 tumor-suppressing genes and the development of four FDA-approved dual PARP1/2 inhibitors for BRCA1/2-deficient cancers (breast, ovarian, pancreatic, and prostate), highlighting the contribution of fundamental discoveries to cancer therapeutics. Recent studies have expanded the functions of PARP1/2 beyond DNA repair and addressed the dose-limiting toxicity of PARP inhibitors in cancer therapy. There is also a growing knowledge of other PARP family members. PARP7 was recently identified in a synergistic lethal screen with histone demethylases mutated in cancer. Notably, > 50% of PARPs, including PARP7, are interferon-inducible. They, including PARP7, PARP11, and PARP14, play critical roles in modulating immune responses in cancer. Several PARP7 inhibitors are in clinical development for cancer therapy, reflecting the growing therapeutic potential of PARP family members beyond PARP1&2. Beyond the writers, recent studies have also expanded to erasers, such as PARG, in RNA ADP-ribosylation dynamics, driven by the development of potent and membrane-permeable selective PARG inhibitors. Marking a significant milestone in the field, PARG inhibitors are the first ADP-ribosylation eraser inhibitors to be evaluated in cancer clinical trials. The unique chemical composition of PAR with both sugar and ribose components renders innovations in chemical biology, structural biology, and mass spectrometry methods critical for studying ADP-ribosylation. This timely and unique meeting will bring together leading experts and emerging investigators to present and discuss cutting-edge research on PARPs and ADP-ribosylation. Sessions will span multiple disciplines, including genetics, chemical biology, and cell biology, and address topics such as DNA repair, immunity, synthetic lethality, and neurotoxicity. Each session will be co-chaired by two prominent scientists. Talks will include invited presentations from established leaders and rising stars and abstracts selected from submitted applications by graduate students, postdoctoral fellows, and junior faculty. We anticipate approximately 180 attendees, with most contributing a talk or poster. This premier meeting will promote innovation and strengthen the global ADP-ribosylation research community by integrating fundamental and translational perspectives and fostering interdisciplinary collaboration between academic and industry scientists.
