Dr Tyson Sharp

Dr Tyson Sharp

BSc (Hons), PhD
Centre: Centre for Molecular Oncology
Centre Lead, Centre for Molecular Oncology
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As Lead for the Centre for Molecular Oncology, I oversee a range of research themes from solid tumour genomics and bioinformatics, molecular diagnostics and biological therapies to, more recently, DNA repair and genome stability.

 

We are particularly focussed on pancreatic, lung, prostate and ovarian cancers as areas of high unmet clinical need, working closely with colleagues in oncology at Barts Cancer Centre to translate discoveries into patient benefit.

 

Research Details

The current research projects within my group originate from our initial identification of LIMD1 as a specific pRB (retinoblastoma protein) binding partner (Sharp TV et al. PNAS 2004).  LIMD1 is on chromosome 3p21.3, often deleted in epithelial cancers. We have also shown that LIMD1 is a bona fide lung cancer tumour suppressor (Sharp TV et al PNAS 2008) and also that loss of LIMD1 expression correlates with poor patient prognosis and decreased survival with respect to breast cancer (Spendlove et al 2008).


The full molecular characterization of this novel tumour suppressor is therefore the main focus of my group’s continued research. By understanding the function(s) of LIMD1 and indeed its family member proteins (Ajuba and WTIP); we can begin to understand how loss of this important tumour suppressor(s) contributes to disease pathogenesis and specifically tumorigenesis.

Profile

I obtained my PhD from St. Georges, University of London. After two postdoctoral positions in The Netherlands and USA, I retuned to take up a Senior Research Fellow position at the Institute of Cancer Research in London and then UCL. I then moved to the University of Nottingham to set up my independent research group in 2005. From there I relocated to BCI. My group studies the role of the LIM domain family of adaptor proteins and their role in regulating microRNA mediates gene silencing and the hypoxic response and how deregulation of these proteins and pathways contribute to disease states including cancer.

Funding

2017 - 2020 Barts Charity Novel Targeted Therapy for Renal Cancer
£337,435
2016 - 2019 Medical Research Council Unravelling the Mechanism of the Lung Tumor Suppressor LIMD1 from Cellular Metabolism to Malignant Transformation
£475,259

2014-
2017

BBSRC

Characterisation of a new mechanism of regulation for HIF1 and the hypoxic response
£419,080

2013

Barts And The London Charity

Investigating a unique hypoxia-LAW-microRNA signalling nexus
£8,910

2013

BBSRC

International Partnering Award
£24,899

2013

Medical Research Council

£44,610

2012-2015

Barts and the London Charity

"Induced Pluripotent Stem Cells as a platform for the study of patient-specific cellular biochemistry and assessment of personalised medicines in cancer, cardiac and endocrinological diseases" (Co-investigator)
£399,387

2012-2015

Cancer Research UK

Project Grant: "Role of LIMD1 loss in lung cancer stem cell biology"
£239,381

2011-2015

BBSRC

Project Grant: "The new LAW of microRNA-mediated gene silencing."
£461,924

2012-2013

BBSRC

Follow on Funding (FoF): "Pre-commercialisation validation of Stem Cell Generator as a highly efficient single transfection iPSC reprogramming vector"
£47,048

Key Publications

Argonaute Utilization for miRNA Silencing Is Determined by Phosphorylation-Dependent Recruitment of LIM-Domain-Containing Proteins. Bridge KS, Shah KM, Li Y, Foxler DE, Wong SCK, Miller DC, Davidson KM, Foster JG, Rose R, Hodgkinson MR, Ribeiro PS, Aboobaker AA, Yashiro K, Wang X, Graves PR, Plevin MJ, Lagos D, Sharp TV. Cell Rep. (2017) 20(1):173-87.  PMID: 28683311

Lentiviral delivery of a vesicular glutamate transporter 1 (VGLUT1)-targeting short hairpin RNA vector into the mouse hippocampus impairs cognition. King MV, Kurian N, Qin S, Papadopoulou N, Westerink BHC, Cremers TI, Epping-Jordan MP, Le Poul E, Ray DE, Fone KCF, Kendall DA, Marsden CA, Sharp TV. Neuropsychpharmacology. 2013 39(2):464-76. PMID: 24037344

The LIMD1 protein bridges an association between the prolyl hydroxylases and VHL to repress HIF-1 activity. Foxler DE, Bridge KS, James V, Webb TM, Mee M, Wong SC, Feng Y, Constantin-Teodosiu D, Petursdottir TE, Bjornsson J, Ingvarsson S, Ratcliffe PJ, Longmore GD, Sharp TVNat Cell Biol. 2012 14(2):201-8. PMID: 22286099

LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for microRNA-mediated gene silencing. James V, Zhang Y, Foxler DE, de Moor CH, Kong YW, Webb TM, Self TJ, Feng Y, Lagos D, Chu CY, Rana TM, Morley SJ, Longmore GD, Bushell M, Sharp TVProc Natl Acad Sci U S A. 2010 107(28):12499-504. PMID: 20616046

The chromosome 3p21.3-encoded gene, LIMD1, is a critical tumor suppressor involved in human lung cancer development. Sharp TV, Al-Attar A, Foxler DE, Ding L, de A Vallim TQ, Zhang Y, Nijmeh HS, Webb TM, Nicholson AG, Zhang Q, Kraja A, Spendlove I, Osborne J, Mardis E, Longmore GD. Proc Natl Acad Sci U S A. 2008 105(50):19932-7. PMID: 19060205

 


 

Further Publications

For additional publications, please click here.


As Lead for the Centre for Molecular Oncology, I oversee a range of research themes from solid tumour genomics and bioinformatics, molecular diagnostics and biological therapies to, more recently, DNA repair and genome stability.

 

We are particularly focussed on pancreatic, lung, prostate and ovarian cancers as areas of high unmet clinical need, working closely with colleagues in oncology at Barts Cancer Centre to translate discoveries into patient benefit.

 

External Activities

Member of the:

  • MRC Peer Review College
  • The Biochemical Society
  • The British Lung Foundation
  • The British Thoracic Society

News

See other researchers working on:

Cancer and Ageing Cell Signalling Lung and Mesothelioma
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