Mammalian cellular metabolism is dynamically regulated in response to changes in cellular state and function and to perturbations in the environment. We integrate metabolomics, lipidomics and metabolic flux analysis with biochemical, genetic, and computational tools to understand metabolism. We are particularly interested in metabolic reprogramming that occurs in specific situations relevant to human health, including the dynamic metabolic remodeling during immune cell activation, and the metabolic adaptations in cancer cells to a stressful tumor microenvironment. We further investigate the mechanisms by which the specific changes in metabolic state can affect cell function, signal, physiology and survival. Understanding this process will bring insights into fundamental questions regarding metabolic regulation, as well as promote the development of metabolic intervention for various diseases.