ITEHP PhD candidate, Beverly deSouza, will present. The mammary gland is unique among mammalian organs in that it undergoes profound remodeling postnatally. Despite extensive study of hormonal control of pubertal mammary gland development, we still poorly understand how metabolism influences the restructuring of mammary tissue. In this talk, I will discuss our surprising discovery that female mice lacking the metabolic regulator sirtuin 4 (Sirt4) fail to develop normal mammary ducts during puberty and are unable to nurse their pups. My dissertation research shows that Sirt4 expression is required in mammary fibroblasts to promote normal ductal development. Fibroblasts orchestrate much of the deposition and remodeling of the extracellular matrix – the noncellular component of tissues that includes collagen. Proper ECM structure is necessary to drive proliferation and expansion of mammary ducts into the surrounding fat pad. Similar proliferative and invasive programming are stimulated by aberrant ECM remodeling in the pathological setting of mammary tumors. This work thus can provide new insights into known associations between metabolic disease and breast pathologies like lactation insufficiency and breast cancer.