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

The regulatory subunits of PI3Kγ control distinct neutrophil responses.

Deladeriere A, Gambardella L, Pan D

Science signaling
8 1937-9145:ra8 (2015)

PMID: 25605974

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

The phosphoinositide 3-kinase isoform PI3Kβ regulates osteoclast-mediated bone resorption in humans and mice.

Győri D, Csete D, Benkő S

Arthritis & rheumatology (Hoboken, N.J.)
66 2326-5205:2210-21 (2014)

PMID: 24719382

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

Regulation of PTEN inhibition by the pleckstrin homology domain of P-REX2 during insulin signaling and glucose homeostasis.

Hodakoski C, Hopkins BD, Barrows D

Proceedings of the National Academy of Sciences of the United States of America
111 1091-6490:155-60 (2014)

PMID: 24367090

Signaling via class IA Phosphoinositide 3-kinases (PI3K) in human, breast-derived cell lines.

Juvin V, Malek M, Anderson KE

PloS one
8 1932-6203:e75045 (2013)

PMID: 24124465

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