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Department of Pathology

 

Klaus Okkenhaug is Professor of Immunology in the Department of Pathology. He obtained his BSc. in Biochemistry from the University of Victoria, British Columbia, Canada, followed by a PhD. in Immunology from the University of Toronto, where he studied CD28 signalling in Robert Rottapel's lab. In 1999, he moved to London, UK, where he joined Bart Vanhaesebroeck's group at the Ludwig Institute for Cancer Research as a Postdoctoral Fellow, working on the role of the PI3Kδ in immune responses. There he generated the PI3Kδ kinase-dead knock-in mouse, which showed a key role for this PI3K isoform in B cell and T cells. Klaus was a group leader at the Babraham Institute from 2003-2017. Klaus has authored more than 100 per-reviewed publications and has made major contributions to the understanding of the roles of PI3K in immunity, infection and cancer. He has also advised several pharmaceutical companies on the development of specific PI3K inhibitors, some of which are now in use clinically.

Immunology
Cell signalling
Immunotherapy
Infection
Cancer

Publications

Key publications: 

Selected recent primary research papers:

 

A CRISPR screen targeting PI3K effectors identifies RASA3 as a negative regulator of LFA-1-mediated adhesion in T cells.
Johansen KH, Golec DP, Huang B, Park C, Thomsen JH, Preite S, Cannons JL, Garçon F, Schrom EC, Courrèges CJF, Veres TZ, Harrison J, Nus M, Phelan JD, Bergmeier W, Kehrl JH, Okkenhaug K, Schwartzberg PL.
Sci Signal. 2022 Jul 19;15(743):eabl9169.
DOI: 10.1126/scisignal.abl9169

 

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 2021. 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 Regulates the Magnitude of CD8+ T Cell Responses after Challenge with Listeria monocytogenes
Pearce VQ, Bouabe H, MacQueen AR, Carbonaro V, Okkenhaug K.
J Immunol. 2015. 195(7):3206-17. 
DOI: 10.4049/jimmunol.1501227

 

Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer
Ali K, Soond DR, Pineiro R, Hagemann T, Pearce W, Lim EL, Bouabe H, Scudamore CL, Hancox T, Maecker H, Friedman L, Turner M, Okkenhaug K, Vanhaesebroeck B.
Nature. 2014. 510(7505):407-411.
DOI: 10.1038/nature13444

 

Phosphoinositide 3-kinase δ gene mutation predisposes to respiratory infection and airway damage
Angulo I, Vadas O, Garçon F, Banham-Hall E, Plagnol V, Leahy TR, Baxendale H, Coulter T, Curtis J, Wu C, Blake-Palmer K, Perisic O, Smyth D, Maes M, Fiddler C, Juss J, Cilliers D, Markelj G, Chandra A, Farmer G, Kielkowska A, Clark J, Kracker S, Debré M, Picard C, Pellier I, Jabado N, Morris JA, Barcenas-Morales G, Fischer A, Stephens L, Hawkins P, Barrett JC, Abinun M, Clatworthy M, Durandy A, Doffinger R, Chilvers ER, Cant AJ, Kumararatne D, Okkenhaug K, Williams RL, Condliffe A, Nejentsev S.
Science. 2013. 342(6160):866-71.
DOI: 10.1126/science.1243292

Other publications: 

Selected Review Articles:

Mind the GAP: RASA2 and RASA3 as gatekeepers of T cell activation and adhesion
Johansen KH, Golec DP, Okkenhaug K, Schwartzberg PL.
Trends in Immunology. 2023. doi: 10.1016/j.it.2023.09.002
 

PI3K in T Cell Adhesion and Trafficking
Johansen KH, Golec DP, Thomsen JH, Schwartzberg PL, Okkenhaug K.
Front Immunol. 2021. 12:708908. doi: 10.3389/fimmu.2021.708908

PI3K inhibitors are finally coming of age
Vanhaesebroeck B, Perry MWD, Brown JR, André F, Okkenhaug K.
Nat Rev Drug Discov. 2021. 14. doi: 10.1038/s41573-021-00209-1.
Full text available here: https://rdcu.be/cmDLM

Phosphoinositide 3‐kinase δ is a regulatory T‐cell target in cancer immunotherapy
EL Lim, K Okkenhaug
Immunology. 2019. 157 (3), 210-218. 
DOI: 10.1111/imm.13082

 

PI3Kδ and primary immunodeficiencies 
Lucas CL, Chandra A, Nejentsev S, Condliffe AM, Okkenhaug K.
Nat Rev Immunol. 2016. 16(11):702-714.  Epub 2016 Sep 12. Review.
DOI 10.1038/nri.2016.93.

 

Targeting PI3K in Cancer: Impact on Tumor Cells, Their Protective Stroma, Angiogenesis, and Immunotherapy
Okkenhaug K, Graupera M, Vanhaesebroeck B.
Cancer Discov. 2016. 6(10):1090-1105. 
DOI: 10.1158/2159-8290.cd-16-0716

 

Teaching and Supervisions

Teaching: 

Professor Okkenhaug teaches the following courses:

Part 1B Biology of Disease (Immunology) 

Part II Pathology (Immunology)

Professor of Immunology
Head of the Division of Immunology
Deputy Head of Department (Research)
Fellow and Postgraduate Tutor at Magdalene College
Klaus Okkenaug
Takes PhD students
Available for consultancy