CSHL 2024 Conference on the PARP Family & ADP-Ribosylation

Cold Spring Harbor Laboratory Conference on The PARP Family and ADP-ribosylation April 3 – 6, 2024 ABSTRACT 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 3 – 6, 2024. ADP-ribosylation is a posttranslational

modification (PTM) of proteins, RNA, and DNA catalyzed by a family of enzymes known as PARPs (17 in humans). PARPs use nicotinamide adenine dinucleotide (NAD+) to catalyze ADP-ribosylation. A curious, and critically important, feature of PARPs is their ability to catalyze two forms of ADP-ribosylation: (i) mono-ADP-

ribosylation (MARylation), which involves the transfer of a single unit of ADP-ribose, and (ii) poly-ADP- ribosylation (PARylation), which involves the transfer of multiple units of ADP-ribose. Similar to other PTMs, ADP-ribosylation is reversible. Indeed, enzymes that reverse PARylation (e.g., PARG, TARG1) and

MARylation (e.g., MacroD2, ARH3) have been identified. In the early days of the PARP field, the focus was solely on PARP1, which revealed critical roles for PARP1 in the DNA damage response (DDR). These studies ultimately lead to the validation of PARP1 as a therapeutic target for the treatment of DDR defective cancers.

To date, there are four FDA-approved PARP1 inhibitors for a subset of breast and ovarian cancers and several more in the pipeline. In several cases, PARP1 inhibitor treatment resulted in distant disease-free survival, demonstrating their tremendous clinical success and how the field has translated fundamental discoveries into

therapeutics. And we are just getting started. Recent studies have expanded our understanding, not only of the role of PARP1 outside of DNA repair but also of the roles of lesser-understood PARP family members in diverse cellular processes, including post-transcriptional and post-translational regulation, protein degradation,

and innate immune signaling. These studies have been advanced with the advent of new technological developments in the field, especially in chemical biology, structural biology, and mass spectrometry. Several PARPs beyond PARP1 have emerged as therapeutic targets not only for cancer but also for inflammation and

infectious diseases. Indeed, inhibitors of PARP7 and PARP14 are currently in clinical development. These are indeed exciting times for the PARP and ADP-ribosylation field, both in terms of the expansion into new areas of physiology and disease and novel therapeutic development. 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. Critically, this unique and timely meeting will bring together scientists from both academia and industry working in various biology and chemistry disciplines, enhancing scientific diversity and providing a good balance between

fundamental and translational research. Each session will be chaired by two leading scientists in the field, both in academia and industry. Longer format, oral presentations will be given by distinguished scientists as well as rising stars in the field. Shorter format, oral presentations will be given by scientists selected from the

abstracts; these will include graduate students, postdoctoral fellows, and junior faculty, aiming for maximal inclusion of young investigators, and importantly scientists from groups historically excluded and underrepresented in the biomedical sciences. 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.