Global analysis of mammalian cell physiology
Ph.D. Student: Woo Suk Ahn
The goal of this project is to extend metabolic flux phenotyping from the study of isolated cells in culture to global analysis of physiology of many cell types in vivo, e.g. liver, muscle, adipose, etc. This research builds on previous work where we used 13C and 2H tracers to quantify glucose fluxes in hepatocytes (liver cells). The focus here will be on applying these and other non-traditional stable isotope tracers to study complex pathways of central carbon metabolism in mammalian systems.
Previously, models of central carbon metabolism that incorporate GC-MS generated 13C-isotopomer data for citric acid cycle related metabolites (e.g. citrate, α-ketoglutarate, malate) have been published for the liver, heart and adipocytes. However, monitoring of this important pathway has been challenging due the presence of multiple cellular compartment. To obtain high-quality data with enough information to resolve these fluxes we will apply novel tandem mass spectrometry tools that are being developed in our lab. Ultimately, these methodologies will provide valuable tools for in vivo studies of human diseases such as type-II diabetes and cancer.
Yoo H, Antoniewicz MR, Stephanopoulos G, Kelleher JK.