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

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

P-Rex1 directly activates RhoG to regulate GPCR-driven Rac signalling and actin polarity in neutrophils.

G Damoulakis, L Gambardella, KL Rossman

Journal of cell science
127 Pt 11:2589-600 (2014)

DOI: 10.1242/jcs.153049

PMID: 24659802

More paths to PI3Kγ.

L Stephens, P Hawkins

PLoS biology
11 6:e1001594 (2013)

DOI: 10.1371/journal.pbio.1001594

PMID: 23853549

Two distinct functions for PI3-kinases in macropinocytosis.

O Hoeller, P Bolourani, J Clark

Journal of cell science
126 Pt 18:4296-307 (2013)

DOI: 10.1242/jcs.134015

PMID: 23843627

Activation of the neutrophil NADPH oxidase by Aspergillus fumigatus.

KB Boyle, LR Stephens, PT Hawkins

Annals of the New York Academy of Sciences
1273 :68-73 (2012)

DOI: 10.1111/j.1749-6632.2012.06821.x

PMID: 23230839

Phosphoinositide 3-OH kinase regulates integrin-dependent processes in neutrophils by signaling through its effector ARAP3.

L Gambardella, KE Anderson, Z Jakus

Journal of immunology (Baltimore, Md. : 1950)
190 1:381-91 (2013)

DOI: 10.4049/jimmunol.1201330

PMID: 23180820

GPCR activation of Ras and PI3Kc in neutrophils depends on PLCb2/b3 and the RasGEF RasGRP4.

S Suire, C Lécureuil, KE Anderson

The EMBO journal
31 14:3118-29 (2012)

DOI: 10.1038/emboj.2012.167

PMID: 22728827

PI3K signalling: the path to discovery and understanding.

B Vanhaesebroeck, L Stephens, P Hawkins

Nature reviews. Molecular cell biology
13 3:195-203 (2012)

DOI: 10.1038/nrm3290

PMID: 22358332

SCFAs induce mouse neutrophil chemotaxis through the GPR43 receptor.

MA Vinolo, GJ Ferguson, S Kulkarni

PloS one
6 6:e21205 (2011)

DOI: 10.1371/journal.pone.0021205

PMID: 21698257