Modelling of Mosaic PIK3CA Related Overgrowth Spectrum (PROS) using induced Pluripotent Stem Cells

10-years ago a series of disorders including asymmetric tissue overgrowth was found to be caused by changes in the PIK3CA gene.

The patchiness of the often life-threatening overgrowth is explained by the gene change happening after conception, so it affects only some cells. The conditions are now known as the “PIK3CA-Related Overgrowth Spectrum” (PROS). The protein made by the PIK3CA gene controls cell growth. In PROS it is active even when cells do not receive “instructions” to grow.

PIK3CA mutations are expected in all cell types, but are very rare seen in blood, but common in blood vessel cells which share a developmental origin. There is also often mismatch between overgrowth severity and the amount of mutation. These observations suggest that PIK3CA regulates blood development, and that mutated cells may influence healthy cells.

This project will study the PIK3CA mutation in human cells mimicking early embryonic cells, called induced Pluripotent Stem Cells (hiPSCs).

I will address whether blood cells are spared from the mutation because affected cells die, or because the mutation directs development away from blood.

I will also study the how mutant influence healthy cells, and will test treatments that my revert the effect of the mutation.