The DeBerardinis laboratory is interested in understanding the metabolic activities that support cell survival, 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 that convert simple nutrients (sugars, amino acids, etc.) into macromolecules (proteins, lipids, and nucleic acids). We believe that these activities are orchestrated by growth factor-stimulated signal transduction pathways, which direct cells to take up abundant nutrients and allocate them into the proper metabolic pathways.
We want to understand how signal transduction impacts metabolism during states of physiological cell proliferation such as embryogenesis, tissue remodeling and activation of the immune system, and during pathological states like cancer and autoimmune diseases. To do this, we use a combination of techniques in molecular biology, cell biology and biochemistry, coupled with metabolic flux analysis using mass spectrometry and NMR spectroscopy. By identifying the crucial metabolic activities that propel pathological cell growth, we hope to develop novel methods to treat cancer and other diseases.
We are also interested in a class of pediatric disorders called the inborn errors of metabolism (IEMs). These are genetic diseases caused by mutations that impair such metabolic pathways as the tricarboxylic acid cycle, the urea cycle, fatty acid and amino acid oxidation, and the electron transport chain. Although many of these conditions can now be detected on the few drops of blood collected from all babies born in the United States, many questions persist about their pathophysiology and treatment. A long-term goal of the lab is to use in vivo and ex vivo metabolic flux analysis to improve the diagnosis and treatment of these children, and to develop novel analytical platforms to identify new IEMs.