We explore…

• The role of NAD metabolism as a therapeutic target in metabolic disease, aging, and cancer: Nicotinamide adenine dinucleotide (NAD) is a redox coenzyme central to energy metabolism and an essential cofactor for non-redox NAD dependent enzymes including sirtuins and poly-ADP-ribose polymerases (PARPs). Recently, lower NAD levels have also been linked to multiple disease states including metabolic disease, cancer, and in aging tissues in both rodents and human patients. Thus, the Covarrubias laboratory will explore how NAD consuming and biosynthetic pathways are altered during these disease states, the biological mechanisms in which altered NAD levels impact metabolism, gene expression and cell biology, and explore NAD metabolism as a potential therapeutic target.

• Exploring the role of nutrient/metabolite levels and nutrient sensing pathways in the regulation of immune cell function: Dr. Covarrubias has made key discoveries showing how metabolite levels are sensed via nutrient sensing signaling pathways, such the Akt-mTOR pathway, to influence macrophage gene expression and inflammatory functions during obesity and lean condition. Conversely, Dr. Covarrubias has shown how macrophage-derived inflammation can influences tissue levels of the critical metabolites including NAD during aging. Thus, the Covarrubias Lab will continue investigating the crosstalk and integration between nutrient/metabolite levels, nutrient sensing signaling pathways, gene expression and immune cell function.

  • Immune cell and senescent cell crosstalk in metabolic disease, aging, and cancer: The Covarrubias Lab hopes to build on the discovery that senescent cells directly influence the function of tissue-resident macrophages via the secretion of the SASP by senescent cells. For example, Dr. Covarrubias showed that exposure to SASP causes macrophages to proliferate, polarize to a pro-inflammatory M1-like state, and alter their metabolism. Thus, the Covarrubias Lab will continue to further characterize and explore how senescent cells influence macrophage biology and aging.