Cold Spring Harbor Laboratory Conference on The PARP Family and ADP-ribosylation April 1 - 4, 2020 Project Summary This proposal seeks support for a meeting on “The PARP Family and ADP-ribosylation” to be held at Cold Spring Harbor Laboratory (CSHL) on April 1 - 4, 2020. ADP-ribosylation is a posttranslational modification of proteins catalyzed by a family of mono- and poly(ADP-ribosyl) transferase enzymes (the PARP family). PARP proteins possess an intrinsic enzymatic activity that catalyzes the transfer of ADP-ribose (ADPR) units from nicotinamide adenine dinucleotide (NAD+) onto target proteins, thereby modulating their activities. Recent studies have highlighted the diverse and important roles of ADP-ribosylation reactions in cellular functions in physiological and pathological states. This is an exciting time for PARPs and ADP- ribosylation, with three FDA-approved PARP inhibitors being used in the clinic for the treatment of cancer and other promising applications being explored. This meeting will assemble leaders in the field, together with junior faculty, postdoctoral fellows and graduate students, to present, review, and discuss current research on PARPs and ADP-ribosylation, especially as they pertain to cancer, inflammation, and metabolic disorders. PARPs and ADP-ribosylation play diverse roles in a broad range of physiological processes (e.g., DNA repair, maintenance of genome integrity, metabolism, hormone signaling, gene regulation, and RNA biology) and pathophysiological processes (cancer, inflammation, stress, metabolic diseases, and aging). This unique and timely meeting will bring together scientists working on different systems and using different approaches. The aims of this meeting are to present, review, and discuss current research covering (1) areas of historical importance to the PARP field, such as the role of nuclear PARPs in DNA repair, as well as emerging roles for nuclear PARPs in gene regulation and RNA biology; (2) non-nuclear PARPs and the mono(ADP-ribosyl) transferases; (3) proteins that functionally interact with PARPs or control NAD+ metabolism; (4) a broad spectrum of biological systems and disease states in which PARPs function, (5) the therapeutic utility of PARP inhibitors in treating diseases, such as cancers, and (6) methodological advances required to address critical remaining questions in the field. In addition, this meeting will provide career development opportunities for trainees and a forum for discussing current issues and planning the future of the PARP field. Each session will be chaired by a leading scientist in the field. Oral presentations will be given by distinguished invited speakers, as well as speakers selected from the abstracts. These will include graduate students, postdoctoral fellows, and junior faculty, aiming for maximal inclusion of young investigators and groups typically underrepresented in the biomedical sciences. Of special importance is the poster session, where many participants can present their work in an atmosphere conducive to informal discussions. We expect about 175 people to attend, with the vast majority presenting a poster or talk. Overall, this meeting - the premier meeting in the PARP field - will support the robust exchange of ideas and promote collaborations.

The PARP Family and ADP-ribosylation Project Narrative ADP-ribosylation reactions, which are catalyzed by a family of mono- and poly(ADP-ribosyl)transferase enzymes (the PARP family), play diverse and important roles in a broad range of physiological processes (e.g., DNA repair, maintenance of genome integrity, metabolism, hormone signaling, and gene regulation) and pathophysiological processes (cancer, inflammation, stress responses, metabolic diseases, and aging). Targeting PARPs with small molecule chemical inhibitors has shown promise as a therapeutic approach in cancers, inflammation, and other disease states. Understanding the molecular mechanisms and biology of PARPs and ADP-ribosylation should provide new opportunities to target PARPs for the prevention and treatment of human diseases.