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.