Metabolism and cancer

In the lab, we are interested in how the metabolic requirements of cancer cells differ from those of normal proliferating cells. In particular, we are focused on understanding the role of pyruvate kinase in cancer metabolism. The pyruvate kinase gene, Pkm, encodes PK-M1 and PK-M2, which are the result of alternative splicing of mutually exclusive exons. Cancer cells universally express the PK-M2 isoform, and their aerobic glycolysis is dependent on PK-M2. This raises an important question regarding the metabolic requirements of cancer cells and the role of PK-M2 in meeting those requirements. We have characterized the expression patterns of PK-M1 and PK-M2 in the developing embryo and in the adult. In addition, we are using a conditional Pkm allele to explore the effects of isoform switching from PK-M2 to PK-M1.

Metabolism and cancer

(Top) Schematic of Pkm pre-mRNA alternative splicing, resulting in Pkm1 and Pkm2. (Bottom) PK-M2 and PK-M1 IHC on serial sections show that at E14.5, the liver (L) does not express PK-M2 or PK-M1 while the heart (H) expresses both isoforms.