Life Sciences Research for Lifelong Health

Len Stephens

The programmes of work in the laboratory are currently aimed at understanding the molecular mechanisms and physiological significance of intracellular signalling networks which involve a family of enzymes called phosphoinositide 3OH-kinases (PI3Ks).

PI3Ks are now accepted to be critical regulators of numerous important and complex cell responses, including cell growth, division, survival and movement.

PI3Ks catalyse the formation of one or more critical phospholipid messenger molecules, which signal information by binding to specific domains in target proteins. Currently the best understood pathway involves the activation of Class I PI3Ks by cell surface receptors.

In recent years, the laboratory has increasingly focused on the role of PI3Ks in the signalling mechanisms which allow receptors on neutrophils (white blood cells) to control various aspects of neutrophil function.

Neutrophils are key players in the front line of our immune system, responsible primarily for the recognition and destruction of bacterial and fungal pathogens. However, they are also involved in the amplification cascades that underlie various inflammatory pathologies, e.g. Acute Respiratory Distress Syndrome (ARDS) and rheumatoid arthritis.

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Latest Publications

Coincident signals from GPCRs and receptor tyrosine kinases are uniquely transduced by PI3Kβ in myeloid cells.

Houslay DM, Anderson KE, Chessa T

Science signaling
9 1937-9145:ra82 (2016)

PMID: 27531651

The inositol-3-phosphate synthase biosynthetic enzyme has distinct catalytic and metabolic roles.

Frej AD, Clark J, Roy CL

Molecular and cellular biology
1098-5549: (2016)

PMID: 26951199

Emerging evidence of signalling roles for PI(3,4)P2 in Class I and II PI3K-regulated pathways.

Hawkins PT, Stephens LR

Biochemical Society transactions
44 1470-8752:307-14 (2016)

PMID: 26862220

Inactivation of the Class II PI3K-C2β Potentiates Insulin Signaling and Sensitivity.

Alliouachene S, Bilanges B, Chicanne G

Cell reports
13 2211-1247:1881-94 (2015)

PMID: 26655903

Investigating the effect of arachidonate supplementation on the phosphoinositide content of MCF10a breast epithelial cells.

Anderson KE, Juvin V, Clark J

Advances in biological regulation
2212-4934: (2015)

PMID: 26639089

Localizing the lipid products of PI3Kγ in neutrophils.

Norton L, Lindsay Y, Deladeriere A

Advances in biological regulation
2212-4934: (2015)

PMID: 26596865

The cytotoxic T cell proteome and its shaping by the kinase mTOR.

Hukelmann JL, Anderson KE, Sinclair LV

Nature immunology
1529-2916: (2015)

PMID: 26551880

The regulatory subunits of PI3Kγ control distinct neutrophil responses.

Deladeriere A, Gambardella L, Pan D

Science signaling
8 1937-9145:ra8 (2015)

PMID: 25605974

PI3K signalling in inflammation.

Hawkins PT, Stephens LR

Biochimica et biophysica acta
1851 0006-3002:882-97 (2015)

PMID: 25514767

Dictyostelium uses ether-linked inositol phospholipids for intracellular signalling.

Clark J,Kay RR,Kielkowska A,Niewczas I,Fets L,Oxley D,Stephens LR,Hawkins PT

The EMBO journal
1460-2075: (2014)

PMID: 25180230