Proper control of intermediary metabolism contributes to the physiology of essentially all human tissues and is perturbed in numerous disease states. Dr. DeBerardinis’s laboratory is interested in understanding how metabolism supports cell growth and proliferation. Cells undergoing replicative division must duplicate their biomass in order to produce daughter cells, and this is made possible through the combined activities of numerous metabolic pathways acting in concert to convert simple nutrients (sugars, amino acids) into macromolecules (proteins, lipids, nucleic acids). These activities are orchestrated by growth factor–stimulated signal transduction, which directs cells to take up nutrients and allocate them into the proper metabolic pathways. The DeBerardinis lab seeks to understand how signal transduction impacts metabolism during physiological cell growth and in pathological states such as cancer. To do this, they use a combination of techniques in molecular biology, cell biology, and biochemistry, coupled with metabolic flux analysis and metabolomics. They are also interested in a class of human diseases called the pediatric inborn errors of metabolism (IEMs). These are rare genetic diseases caused by mutations in the tricarboxylic acid cycle, the urea cycle, fatty acid and amino acid oxidation, the electron transport chain, and other pathways. Although many of these diseases are detected in presymptomatic babies through newborn screening, many questions persist about pathophysiology and treatment. A long-term goal of the lab is to use in vivo metabolic flux analysis to improve the diagnosis and treatment of children with IEMs.
Ralph J. DeBerardinis, MD, PhD