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Department of Pathology

 
Diagram explaining PI3K in immunity, infection and cancer

Our research

Our group focuses on how a group of enzymes called phosphoinositide 3-kinases (PI3Ks) which 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, each of which can generate second messenger signalling molecules within cells that control diverse of cellular functions and genetic programmes.

We aim 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 and cancer.

Most of our work to date has focused on PI3Kδ. The activation of PI3Kδ 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 PI3Kδ is expressed at very low levels in other organs in the body, t targeting PI3K 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 PI3Kδ or other forms of PI3K to help predict and understand the effect of such drugs on the immune system.

Recent Publications

PI3Kδ Forms Distinct Multiprotein Complexes at the TCR Signalosome in Naïve and Differentiated CD4 + T Cells

Luff DH, Wojdyla K, Oxley D, Chessa T, Hudson K, Hawkins PT, Stephens LR, Barry ST, Okkenhaug K.
Frontiers in Immunology 12, 415
DOI: 10.3389/fimmu.2021.631271

Loss of Phosphatidylinositol 3-Kinase Activity in Regulatory T Cells Leads to Neuronal Inflammation

Stark AK, Davenport ECM, Patton DT, Scudamore CL, Vanhaesebroeck B, Veldhoen M, Garden OA, Okkenhaug K.
J Immunol. 2020. 205 (1) 78-89.
DOI: 10.4049/jimmunol.2000043

PI3Kδ hyper-activation promotes development of B cells that exacerbate Streptococcus pneumoniae infection in an antibody-independent manner

Stark AK, Chandra A, Chakraborty K, Alam R, Carbonaro V, Clark J, Sriskantharajah S, Bradley G, Richter AG, Banham-Hall E, Clatworthy MR, Nejentsev S, Hamblin JN, Hessel EM, Condliffe AM, Okkenhaug K.
Nat Commun. 2018. 9(1):3174. 
DOI: 10.1038/s41467-018-05674-8

Phosphoinositide 3-kinase δ inhibition promotes antitumor responses but antagonizes checkpoint inhibitors

Lim EL, Cugliandolo FM, Rosner DR, Gyori D, Roychoudhuri R, Okkenhaug K.
JCI Insight. 2018. 3(11). pii: 120626. 
DOI: 10.1172/jci.insight.120626

PI3Kδ promotes CD4(+) T-cell interactions with antigen-presenting cells by increasing LFA-1 binding to ICAM-1

Garçon F and Okkenhaug K.
Immunol Cell Biol. 2016. 94(5):486-95.  
DOI: 10.1038/icb.2016.1