Research Projects / Future Directions

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Oncogenic signaling and cellular metabolism

Altered cellular metabolism is a hallmark of cancer. Cancer cells undergo a marked shift towards aerobic glycolysis ("the Warburg effect"), which reassigns ATP generation from the Krebs cycle to glycolysis and enables reprogramming of the mitochondria from energy production towards anabolic processes. This shift is essential to sustain the limitless proliferative capacity of cancer cells through de novo synthesis of nucleotides and lipids. The glycolytic phenotype of cancer permits non-invasive molecular imaging of many cancers, including glioblastoma, by Positron Emission Tomography (PET) using the glucose analog [18F]FDG. It also has a profound impact on tumor cell proliferation and survival through its effects on membrane biogenesis and modification of membrane proteins. The Mischel lab aims to elucidate the molecular circuitry linking oncogenic signaling with altered glioblastoma cellular metabolism in patients and model systems, and identify new molecularly targeted approaches based on disrupting this circuity. The Mischel laboratory has recently demonstrated a key role for AMPK in regulating the growth of EGFR-activated GBMs (Guo et al., PNAS, 2009). The Mischel laboratory has also recently found that inhibitors of fatty acid signaling promote apoptosis in glioblastoma cells with highly active EGFR signaling (Guo et al., Sci. Signaling, 2009).