RESEARCH SUMMARY

Two biological problems have occupied the activity of our team (~12 to 15 members): cancer and inflammation. Our recent work is based in the assumption that the same biological activities that control physiological responses also control pathology when deregulated. The team is currently working on class I phosphoinositide 3-kinase (PI3K), with special emphasis on examining the specific function of each of the four class I PI3K isoforms in physiology and disease.

In cancer, we have recently shown that:

• SADB kinase (which binds PI3K) controls centrosome duplication
• PI3K ubiquitous isoforms PI3KCA and CB have different functions in cell division; PI3KCA regulates cell cycle entry and PI3KCB regulates DNA replication
• Interference with PI3K expression reduces cancer in vivo.

These studies contributed to show that PI3K is a target for cancer treatment and revealed an unexpected nuclear function for PI3KCB.

In inflammation, we previously showed that activation of T cells in vivo (in mouse) induced by deregulated PI3K activation triggers a lupus-like disease similar to human systemic lupus erythematosus (SLE), and that deletion or pharmacological inhibition of PI3KCG in the mouse inhibits lupus. In addition, PI3K activation is frequent in human SLE.

Our recent findings show that PI3K involvement in chronic inflammatory disease is due at least in part to its capacity to mediate memory T cell survival.

These studies contribute to show that haematopoietic PI3K isoforms are a target for chronic inflammatory disease treatment; we are currently studying human SLE.