Sarcomas are a rare group of over 100 types of tumors of mesenchymal origin that can be divided into 2 categories: soft tissue sarcomas and bone sarcomas. Our main objective is to delineate the molecular and genetic events underlying sarcoma pathogenesis. We work to identify metabolic deficiencies in sarcoma that can be used as therapeutic opportunities. We also generate new models that reflect the disease in patients by establishing pedigreed xenografts in immuno-deficient mice and their corresponding cell lines. Additionally, we study argininosuccinate synthase 1 (ASS1), a biomarker that is lost and is a sign of poor prognosis for sarcoma. When ASS1 is not expressed, arginine becomes an essential amino acid that must be delivered by the diet. We are testing whether the ASS1-deficiency of sarcomas may be exploited using the arginine-lowering agent, PEGylated arginine deiminase (ADI-PEG20). We have shown that we can use arginine starvation to change the metabolic transporter profile on the surface of cells, thus allowing chemotherapy to work. We are presently working to better delineate the in vivo adaptation that occurs in tumors.