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FINDING CURES TOGETHER<sup>SM</sup>

AACR Gertrude B. Elion Cancer Research Award

The AACR Gertrude B. Elion Cancer Research Award is open to tenure-track scientists at the level of assistant professor, who completed postdoctoral studies or clinical research fellowships no more than four years prior to the start of the grant term.

2014 Grantee

Matthew Vander Heiden, MD, PhDMatthew Vander Heiden, MD, PhD
Assistant Professor, Department of Biology, Massachusetts Institute of Technology-Koch Institute for Integrative Cancer Research, Cambridge, MA

The Role of Serine Metabolism in Melanoma

Better models to study cancer metabolism in vivo are needed to target altered cell metabolism for cancer therapy. Serine production from glucose is a particularly important metabolic pathway in human cancers. The gene encoding the first enzyme of the serine biosynthesis pathway, PHGDH, is amplified in human melanoma and allows these cancer cells to increase serine synthesis. To study this metabolic alteration, a mouse model will be generated to control PHGDH expression and study the impact of increased serine synthesis on melanoma progression and metabolism.  In this model, the PHGDH allele will be crossed with a mutant BRAF allele to recapitulates the same genetic events observed in the human disease.  This model will be used to determine whether PHGDH is required for melanoma initiation and/or maintenance, and to study how increased serine biosynthesis influences cell metabolism to promote melanoma tumor growth. In these studies, state of the art isotope tracer methods will be employed to study how increased serine synthesis contributes to tumor progression and determine how this pathway should be targeted in the clinic.

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