Development and Implementation of Advanced Technologies for Cancer Metabolism Research

PROJECT SUMMARY This proposal requests support for my position as the Director of the Cancer Metabolism Core at Sanford Burnham Prebys Medical Discovery Institute (SBP). The Core is part of the NCI-designated Cancer Center at SBP. Dr. Ze’ev Ronai, with whom I have worked for thirteen years, is the Cancer Center Director and the Unit Director for this application. The Core supports cancer research by providing a GC-MS-based stable-isotope (13C) metabolite tracing and quantification service. I have worked at SBP on stable-isotope tracer technology since 2008, first in a research lab and for the last six years in the Cancer Metabolism Core. I have developed assays using differing derivatization protocols and MS ionization approaches for polar metabolites, fatty acids (long- and short-chain), cholesterol, sugars and sugar-phosphates, including methods for metabolite quantification and quality control. In the past five years, the Core has contributed to at least 18 papers from labs with NCI project grant support, and I have been a co-author on 13 of these papers. I describe plans in this application for continued expansion of stable isotope tracing methods and metabolite quantification using a newly-acquired GC-MS/MS that will improve detection sensitivity both through the triple quad technology and by being easier to use with chemical ionization. I also plan to work on specific methods needed for cancer research, including for bile acids, oxysterols, hexosamine pathway intermediates, and methods for isolated cell populations and organelle metabolomics. Funding from this R50 award will further allow me to work on the development of targeted LC-MS assays for metabolites that cannot be measured using GC-MS. By strengthening facilities for analysis of altered metabolic states within cancer cells and tumors, this award will advance the goal of excellence in translational multi-disciplinary research in the SBP Cancer Center.