<span style="font-size: 19.2px;"> – The goal of this project is to characterize the metabolic response to arginine deprivation in sarcomas that lack argininosuccinate synthase 1 (ASS1), an enzyme that aids in endogenous arginine production, thus making these tumors arginine auxotrophic. We are trying to identify additional points of therapeutic intervention that induce a synthetic lethal response when targeting sarcoma tumors, in combination with arginine depletion using pegylated arginine deiminase (ADI-PEG20).
– Osteosarcoma is the most common type of primary malignant bone tumor. Current treatment regimens use high-dose methotrexate, which targets the folate pathway by inhibiting dihydrofolate reductase, as part of a pathway that converts serine to purines. We hypothesized that inhibition of PHGDH, the rate-limiting step in serine biosynthesis, would be active for the treatment of osteosarcoma, and are exploring methods of inhibiting the resulting survival pathways to develop novel therapies for osteosarcoma.
– Our lab has shown that many sarcomas deficient in ASS1 are able to evade cell death over time, even when treated with ADI-PEG20. This project focuses on understanding fatty acid metabolism by identifying lipid localization, recycling, and response of cells to inhibition of beta oxidation.
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