The major focus of Dr. Singer's research effort is the development of a novel clinically relevant biochemical and molecular system of prognostic determinants for soft tissue sarcoma. His laboratory is the first to apply novel ex vivo magic angle spinning nuclear magnetic resonance (NMR) spectroscopy methods to examine the biochemical state of tissue lipid and important mediators of cellular lipid metabolism for the most common histologic types of sarcoma.
These studies are focused on using NMR to evaluate the content, composition, and diffusion characteristics of membrane lipid and glycolipid, and relate this biochemical analysis to sarcoma tissue cellularity, proliferation, extent of differentiation, apoptosis, and the propensity for the sarcoma to metastasize. A major goal of this work is to compare sarcoma lipid analysis with conventional histologic grading to see if quantitative biochemical profiles of tissue lipid improve prognostication compared with standard clinicopathologic predictors (grade, size, and histology).
In his NMR laboratory, Dr. Singer is developing new methods for predicting and monitoring response of sarcoma to therapies that are based on a quantitative biochemical analysis of sarcoma apoptosis and differentiation. This integrated computational approach to the analysis of complex molecular and biochemical markers grapples with one of the major issues in applying solid tumor biology to support clinical management decisions: How do we utilize / discriminate from the multivariable biological parameters available?
Many believe that future therapy will be "targeted" to specific abnormalities in the tumor. To utilize such targeted therapy, novel methods of examining tumor composition for specific targets are needed. While many approaches involve new gene discovery, there is considerable evidence that protein and lipid metabolite abnormalities can be targeted to enhance treatment response. The results from this proposal would ultimately enable the identification of new targets and would provide a more rational approach to selecting combination chemotherapy based on an understanding of protein and lipid metabolism along with solid tumor molecular genetics.
