Projects in the laboratory
What are the individual roles of each of the class I PI3Ks in lymphocytes?Using genetic and pharmacological approaches, we address the functions of individual PI3K isoforms in lymphocytes. At the molecular level, we investigate the basis for their differential engagement by the TCR, BCR and other receptors expressed by lymphocytes. We are especially interested in delineating how p110α and p110δ are differentially activated.
How do PI3Ks regulate immune responses to infection?Using different models of infection, the effect of inhibiting PI3K on protective immune responses will be investigated. This will involve analysis of both APCs and responding T cells and B cells using pathogens such as Listeria monocytogenes and Streptococcus pneumoniae. The understanding of how PI3Ks control susceptibility to infection is made more pertinent by the discovery that activating mutations in the gene for p110δ are the cause of a primary immunodeficiency disease (APDS).
What is the role of PI3K signalling in regulatory T cells?We have previously shown that inhibition of p110δ in regulatory T cells (Treg) renders ineffective in preventing T cell-mediated inflammation of the large intestine. More recently we showed that deletion of p110δ in Treg improves immune-mediated rejection of cancer cells. We are currently exploring further consequences of inhibiting PI3K isoforms specifically in Treg and how PI3Ks affect Treg function.
Corrigendum: Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer.
Ali K, Soond DR, Piñeiro R
Inhibition of Phosphoinositide 3-Kinase p110delta Does Not Affect T Cell Driven Development of Type 1 Diabetes Despite Significant Effects on Cytokine Production.
Barbera Betancourt A, Emery JL, Recino A
11 1932-6203:e0146516 (2016)
PI3Kδ promotes CD4(+) T cell interactions with antigen presenting cells by increasing LFA-1 binding to ICAM-1.
Garçon F, Okkenhaug K
Immunology and cell biology
Roychoudhuri R, Eil RL, Clever D
The Journal of clinical investigation
Okkenhaug K, Roychoudhuri R
8 1937-9145:pe3 (2015)
Okkenhaug K, Burger JA
Current topics in microbiology and immunology
393 0070-217X:123-42 (2016)
Sauer K, Okkenhaug K
Frontiers in immunology
6 1664-3224:410 (2015)
Pearce VQ, Bouabe H, MacQueen AR
Journal of immunology (Baltimore, Md. : 1950)
Browning MJ, Chandra A, Carbonaro V
Journal of medical genetics
52 1468-6244:856-9 (2015)
Stark AK, Sriskantharajah S, Hessel EM
Current opinion in pharmacology
23 1471-4973:82-91 (2015)
Immunomodulation of Selective Naive T Cell Functions by p110δ Inactivation Improves the Outcome of Mismatched Cell Transplantation.
Doisne JM, Hüber CM, Okkenhaug K