NAD Metabolism and Signaling

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DESCRIPTION (provided by applicant): The vitamin B3-derived metabolite, nicotinamide adenine dinucleotide (NAD), and its related metabolites, NADH, NADP and NADPH, are best known as co-enzymes for hydride transfer enzymes that play central roles in cellular energy metabolism. It was largely believed that NAD and its related metabolites were too abundant to function in a signal transduction capacity and that they were therefore unlikely to be involved in regulating cellular functions. However, with the more recent discoveries showing that NAD is consumed by enzymes that deacetylate lysine and generate putative signaling metabolites (sirtuins), that post-translationally modify protein targets by ADP-ribosylation via poly ADP ribose polymerases (PARPs) and mono ADP ribosyltransferases (ARTs) and that regulate cell signaling by generating calcium-mobilizing metabolites from NAD and NADP (CD38 and ADP-ribosyl cyclases), it is now clear that NAD metabolism plays a more complex role in cells than previously appreciated. Indeed, the enzymes that catabolize NAD as well as those that contribute to its synthesis and salvage are now known to be global regulators in key aspects of biology from DNA repair to gene transcription and from cancer biology to aging. Recent research has highlighted the many ways in which these NAD-dependent processes intersect, making it clear that a more global systems-wide view of NAD metabolism is central to understanding how the individual processes are regulated. Although scientists can attend conferences that focus on a single aspect of NAD biology, conferences that focus on the NAD metabolome as a whole are not readily available. Thus, there is a need for a conference that brings together the leading scientists working in all areas of the NAD metabolome. The upcoming FASEB summer conference "NAD metabolism and signaling" will meet this need by covering all aspects of NAD biology. Participants and speakers will include those working in the areas of NAD enzymology, biochemistry, signal transduction, structural biology, DNA repair, transcription, nutrition, cell biology, physiology, immunology/inflammation, cancer biology, aging and clinical applications that include a new paradigm for cancer drug discovery. Topics covered in the meeting will include NAD biosynthesis and metabolism, sirtuin, PARP, ART and CD38-mediated signaling and gene regulation, NAD-dependent crosstalk and therapeutic modulation of the NAD metabolome. The major goals of this conference are to foster new interactions between scientists that do not normally meet one another in the course of their work and to promote interdisciplinary interactions that will lead to new collaborations that will advance the field and facilitate development of new therapies. We expect that the scientific insights generated during the course of this meeting will result in the beginning of a systems-wide approach to evaluating the role of the NAD metabolome in cancer, aging, metabolic syndrome and inflammation. The objective of this proposal is to seek funds to support the conference fees for outstanding young investigators, with a particular emphasis on individuals that are under-represented in science. PUBLIC HEALTH RELEVANCE: The proposed meeting "NAD metabolism and signaling" is relevant to public health in that it will focus on establishing the cornerstones for a systems-wide approach to evaluating the role of the NAD metabolome in cancer, aging, obesity and inflammation. This is important to the mission of the NIH because the insights gained from this meeting may lead to the development of new diagnostics and treatments for diseases such as cancer and diabetes that affect the health and well-being of all US citizens.