Life Sciences Research for Lifelong Health

Klaus Okkenhaug

Our group focuses on how a group of enzymes called phosphoinositide 3-kinases (PI3Ks) are used by cells of the immune system to instruct and coordinate defences against pathogens. Cells of the immune system can express up to eight different forms of PI3K, which act as second messenger signalling molecules within cells that control diverse of cellular functions and genetic programmes. Our group tries to dissect the unique roles played by individual forms of PI3K with particular focus on their roles in B cells and T cells. We also ask what the effect of inhibiting or enhancing the activity of individual forms of PI3K has on immunity to infections.

Most of our work to date has focused on a form called p110δ. The activation of p110δ is one of the first events that happen inside a T cell or B cell when it first is exposed to a foreign antigen. Because p110δ is expressed at very low levels in other organs in the body, it is thought that targeting p110δ with drugs may be an effective way to suppress immune responses without some of the side effects associated with many immunosuppressive drugs in current use. We therefore work closely with colleagues in pharmaceutical companies who have developed specific inhibitors against p110δ or other forms of PI3K to help predict and understand the effect of such drugs on the immune system.

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Latest Publications

PI3K Signaling in B Cell and T Cell Biology.

Okkenhaug K, Turner M, Gold MR

Frontiers in immunology
5 1664-3224:557 (2014)

PMID: 25404931

Haematological cancer: Idelalisib-targeting PI3Kδ in patients with B-cell malignancies.

JA Burger and K Okkenhaug

Nature Reviews Clinical Oncology
11 :184-186 (2014)

DOI: 10.1038/nrclinonc.2014.42

PMID: 24642682

IL-21 promotes CD4 T cell responses by phosphatidylinositol 3-kinase-dependent upregulation of CD86 on B cells.

Attridge K, Kenefeck R, Wardzinski L

Journal of immunology (Baltimore, Md. : 1950)
192 1550-6606:2195-201 (2014)

PMID: 24470500

Gene targeting in mice: a review.

H Bouabe, K Okkenhaug

Methods in molecular biology (Clifton, N.J.)
1064 :315-36 (2013)

DOI: 10.1007/978-1-62703-601-6_23

PMID: 23996268

Rules of engagement: distinct functions for the four class I PI3K catalytic isoforms in immunity.

K Okkenhaug

Annals of the New York Academy of Sciences
1280 :24-6 (2013)

DOI: 10.1111/nyas.12027

PMID: 23551098

Signaling by the phosphoinositide 3-kinase family in immune cells.

K Okkenhaug

Annual review of immunology
31 :675-704 (2013)

DOI: 10.1146/annurev-immunol-032712-095946

PMID: 23330955

PDK1 regulation of mTOR and hypoxia-inducible factor 1 integrate metabolism and migration of CD8+ T cells.

Finlay DK, Rosenzweig E, Sinclair LV

The Journal of experimental medicine
209 1540-9538:2441-53 (2012)

PMID: 23183047