Biology of Phosphoinositide 3-Kinases

My laboratory studies the physiological functions and pathological roles of PI3Ks. This family of lipid kinases produces the intracellular second messenger phosphatidylinositol 3,4,5-trisphosphate that regulates diverse cellular functions. We are currently investigating two research aims: 1) the role of PI3K in the development and progression of pancreatic cancer, and 2) the role of PI3K in regulating the function of cardiac ion channels. 

Abnormal upregulation of PI3K signaling is one of the most common oncogenic contributors in the development of human cancers.  We discovered that the p110α isoform of PI3K is essential for the initiation of pancreatic cancer caused by oncogenic Kras (Wu, et al. Gastroenterology 2014).  We are now investigating the role of p110α in the maintenance and progression of pancreatic cancer.

We reported that downregulation of p110α signaling due to drug inhibition or diabetic conditions changes multiple ion currents in cardiac myocytes that result in prolongation of the QT interval on the ECG (Lu et al., Science Translation al Medicine, 2012). QT prolongation in humans can increase the risk of fatal ventricular arrhythmias.  We are now studying the mechanisms by which PI3K signaling regulate cardiac ion channel function.