Cancer Cell Biology
Area of interest
Signaling and genetics related to AMP-activated protein kinase and small molecule chemical probe development for metabolic disorders.
Abnormal metabolism is a well-known trait of cancer cells including the Warburg effect, which describes the preferential usage of glycolysis as an energy source over mitochondrial respiration. Despite significant progress in identifying altered molecular pathways in cancer, the connections between abnormal cellular metabolism and cancer require further elucidation. Originally, the Warburg effect was dismissed as a survival mechanism in low oxygen tumor micro-environments, but even cancer cells grown in high oxygen preferentially utilize glycolysis for still unknown reasons.
AMPK (AMP-activated protein kinase) occupies a unique position as a kinase capable of measuring cellular energy and stress statuses and directly modulating both metabolic and developmental pathways. AMPK serves as a cellular energy gauge that can turn on energy producing activities while simultaneously inhibiting energy consuming activities during times of energetic or oxidative stress. AMPK is also proposed to synergize with the activities of numerous known human tumor suppressors including LKB1, PTEN, and TSC1/2, while inhibiting potential oncogenes including AKT, mTOR, and PI3 kinase. Thus AMPK may serve as key coupling regulator between cellular metabolism and cell division.
Our lab uses both genetics and biochemical/proteomic techniques to understand how AMPK functions both in cells and in organisms. We use the power of Drosophila genetics as a major platform for discovery projects. However, we also have mouse knockouts for AMPK activity that allow us to do cell culture and mammalian genetics as well. We are particularly interested in discovering new molecular players in the AMPK signaling pathway.
Awards and Honors
- American Heart Association Predoctoral fellowship, 6/96 8/97
- Hot Paper in The Scientist for field of Cell Biology for original research publication with extraordinary number of citations (Cell 84, 757-767), 1998
- NIH postdoctoral fellowship, 9/97-7/98
- Damon Runyon-Walter Winchell Cancer Foundantion Postdoctoral Fellowship, 8/98-7/01
- Whitehall Foundation Fellow (2003-2008)
- Searle Scholar award (2003-2005)
- FRAXA award 2003-2004
- Juvenile Diabetes Research Foundation Innovative Grant Award, 2006