Christian Metallo, Ph.D.
Professor, Molecular and Cell Biology Laboratory, at Salk Institute for Biological Studies
Adjunct Professor, Bioengineering at UC San Diego
Seminar Information
Metabolism is central to virtually all cellular functions and contributes to a range of diseases. A quantitative understanding of how biochemical pathways are dysregulated in the context of diseases such as cancer, metabolic syndrome, and neuropathy is necessary to identify new therapeutic targets. To this end we apply stable isotope tracers, mass spectrometry, and metabolic flux analysis (MFA) to explore metabolism in cells, animal models, and human patients. We are particularly interested in understanding how amino acid and lipid metabolism are coordinated in the context of cancer and diabetes. Serine, glycine and one carbon metabolism is critically important for cell function and health, but the amino acids associated with this pathway are commonly reduced in patients with metabolic syndrome. Here I will detail how we apply MFA and related methods to decipher why serine and glycine are reduced in mouse models of diabetes. At the same time, restricting dietary serine and glycine in a high-fat diet promotes neuropathy in C57BL/6 mice. In turn, supplementation of serine improves sensory function in diabetic animals, suggesting potential therapeutic strategies for treating patients with serine-associated neuropathy. We also provide evidence that fatty acyl-CoA diversity in sphingolipid biosynthesis impacts trajectories to insulin resistance/obesity and cardiotoxicity in mice. Collectively, these data provide mechanistic insights into the roles of serine palmitoyltransferase, amino acid metabolism, and fatty acid diversity in driving co-morbidities of diabetes.
Christian Metallo is a professor at the Salk Institute and holds the Daniel and Martina Lewis Chair. He is an adjunct professor in Bioengineering at UC San Diego, where he held a primary faculty appointment for 10 years before moving to Salk. His laboratory integrates engineering approaches, stable isotope tracing, mass spectrometry, and molecular biology tools to dissect how metabolic dysregulation contributes to human disease. Key focus areas include cancer and diabetes co-morbidities, where they draw on genetic and metabolic insights from patients with rare diseases.