Exploring a potentially unique, general mechanism of regulating PI3-kinase signaling implicated in cancer by live cell imaging and biophysical approaches.


Cancer is a very devastating disease: more than one in three people in the UK will develop cancer in their lifetime (2011, Cancer Research UK). PI3-kinase is frequently mutated in cancer and regulates key processes including chemotaxis, cell growth, proliferation, and survival. The lipid product of PI3-kinase, Phosphatidylinositol (3,4,5)-trisphosphate (PIP3), controls these pathways by recruiting downstream effectors containing PIP3 binding PH domains. In this project we will characterize a potentially unique, novel, and general mechanism of regulating the recruitment of PH domain-containing effectors to the lipid PIP3 by a combination of confocal live cell imaging, bioinformatics, and biophysical approaches.

ject details are protected. Please login with a valid account to view them.


PTEN and the PI3-kinase pathway in cancer. Chalhoub N, Baker SJ. Annu Rev Pathol. 2009;4:127-50. doi: 10.1146/annurev.pathol.4.110807.092311. Review.


Membrane recognition by phospholipid-binding domains. Lemmon MA. Nat Rev Mol Cell Biol. 2008 Feb;9(2):99-111. doi: 10.1038/nrm2328. Review. PMID: 18216767 [PubMed - indexed for MEDLINE]


Structural basis for discrimination of 3-phosphoinositides by pleckstrin homology domains. Ferguson KM, Kavran JM, Sankaran VG, Fournier E, Isakoff SJ, Skolnik EY, Lemmon MA. Mol Cell. 2000 Aug;6(2):373-84.


Comprehensive identification of PIP3-regulated PH domains from C. elegans to H. sapiens by model prediction and live imaging. Park WS, Heo WD, Whalen JH, O'Rourke NA, Bryan HM, Meyer T, Teruel MN. Mol Cell. 2008 May 9;30(3):381-92. doi: 10.1016/j.molcel.2008.04.008.


Lamellipodin, an Ena/VASP ligand, is implicated in the regulation of lamellipodial dynamics. Krause M, Leslie JD, Stewart M, Lafuente EM, Valderrama F, Jagannathan R, Strasser GA, Rubinson DA, Liu H, Way M, Yaffe MB, Boussiotis VA, Gertler FB. Dev Cell. 2004 Oct;7(4):571-83.

Biological Areas:

Cell Biology
Structural Biology


Molecules, cells and industrial biotechnology