Sharpe Group

Sharpe Group
Sharpe Group
Hayley Sharpe
Tenure Track Group Leader
Sharpe Group

We are interested in understanding how the cells that make up our tissues and organs communicate. Our cells are decorated with proteins, or receptors, that can sense alterations in their local environment and promote signalling pathways leading to changes in behaviour such as growth, movement or attachment. We focus on receptors that communicate to the cell interior through an enzyme known as a protein phosphatase. These receptor tyrosine phosphatases can change the function of other proteins by catalysing the removal of phosphate groups. The principles of how these receptors contribute to signalling remain poorly understood.
 

The receptor tyrosine phosphatases are linked to diverse areas of biology from immune cell signalling to blood vessel development to cell-cell adhesion, with some implicated in disease processes such as spinal cord injury, wound healing and cancer. Importantly, protein tyrosine phosphatases are targets of reactive oxygen species, which serve as critical signalling molecules that can be dysregulated in ageing and disease. To understand the normal and pathological functions of phosphatases we use biochemistry, proteomics, primary and cancer cell lines, as well as mouse models.
 

 

Latest Publications

Yurchenko AA, Pop OT, Ighilahriz M, Padioleau I, Rajabi F, Sharpe HJ, Poulalhon N, Dreno B, Khammari A, Delord M, Alberdi A, Soufir N, Battistella M, Mourah S, Bouquet F, Savina A, Besse A, Mendez-Lopez M, Grange F, Monestier S, Mortier L, Meyer N, Dutriaux C, Robert C, Saïag P, Herms F, Lambert J, de Sauvage F, Dumaz N, Flatz L, Basset-Seguin N, Nikolaev SI Signalling

Vismodegib is approved for the treatment of locally advanced basal cell carcinoma (laBCC), but some cases demonstrate intrinsic resistance (IR) to the drug. We sought to assess the frequency of IR to vismodegib in laBCC and its underlying genomic mechanisms.

+view abstract Clinical Cancer Research, PMID: 35078858 25 Jan 2022

Drissi I, Fletcher E, Shaheen R, Nahorski M, Alhashem AM, Lisgo S, Fernández-Jaén A, Schon K, Tlili-Graiess K, Smithson SF, Lindsay S, J Sharpe H, Alkuraya FS, Woods G Signalling

Holoprosencephaly is a spectrum of developmental disorder of the embryonic forebrain in which there is failed or incomplete separation of the prosencephalon into two cerebral hemispheres. To date, dominant mutations in sonic hedgehog (SHH) pathway genes are the predominant Mendelian causes, and have marked interfamilial and intrafamilial phenotypical variabilities.

+view abstract Journal of medical genetics, PMID: 33820834 05 Apr 2021

Young KA, Biggins L, Sharpe HJ Signalling

Adhesive structures between cells and with the surrounding matrix are essential for the development of multicellular organisms. In addition to providing mechanical integrity, they are key signalling centres providing feedback on the extracellular environment to the cell interior, and vice versa. During development, mitosis and repair, cell adhesions must undergo extensive remodelling. Post-translational modifications of proteins within these complexes serve as switches for activity. Tyrosine phosphorylation is an important modification in cell adhesion that is dynamically regulated by the protein tyrosine phosphatases (PTPs) and protein tyrosine kinases. Several PTPs are implicated in the assembly and maintenance of cell adhesions, however, their signalling functions remain poorly defined. The PTPs can act by directly dephosphorylating adhesive complex components or function as scaffolds. In this review, we will focus on human PTPs and discuss their individual roles in major adhesion complexes, as well as Hippo signalling. We have collated PTP interactome and cell adhesome datasets, which reveal extensive connections between PTPs and cell adhesions that are relatively unexplored. Finally, we reflect on the dysregulation of PTPs and cell adhesions in disease.

+view abstract The Biochemical journal, PMID: 33710332 12 Mar 2021

Group Members

Hayley Sharpe

Tenure Track Group Leader

Roksana Dutkiewicz

PhD Student

Tiffany Lai

PhD Student

Lauren Maggs

PhD Student

Katie Mulholland

Postdoc Research Scientist

Oisharja Rahman

Research Assistant

Katarzyna Wojdyla

Postdoc Research Scientist

Katherine Young

PhD Student