Professor Tyson V. Sharp

Professor Tyson V. 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 variety of basic cancer cell biology and translation research themes ranging from DNA repair and genome stability, RNA biology including localisation, splicing and microRNA-silencing, to cancer cell metabolism/hypoxia, pre-clinical imaging, drug development and computational bioinformatics.

Our work focuses on basic biology, the identification of biomarkers for cancer diagnosis and treatment, and the development of new targeted therapies, including immune-oncology and oncolytic virotherapy.

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. We have also iniated new studies into targeting LIMD1 negative cancers and also the interplay of LIMD1 and LIM-domain protein with Immune-Oncology.

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.

PhD Studentships within the Sharp Group

Candidates interested in joining the lab to work in this research area can contact Dr Sharp by sending an email to t.sharp@qmul.ac.uk.

Currently positions are only available to self-funded students. QMUL Principal's Postgraduate Research Studentships are available to international students of any nationality and provide funding for up to 3 years of PhD study.

For more information on studentships for both home and international students, please visit here.

Profile

I obtained my PhD from St. Georges, University of London. After two postdoctoral positions in The Netherlands and USA, I returned 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

  • Cancer Research UK
  • Medical Research Council
  • Biotechnology and Biological Sciences Research Council
  • Barts Charity

Key Publications

A HIF-LIMD1 negative feedback mechanism mitigates the pro-tumorigenic effects of hypoxia. Foxler DE, Bridge KS, Foster JG, Grevitt P, Curry S, Shah KM, Davidson KM, Nagano A, Gadaleta E, Rhys HI, Kennedy PT, Hermida MA, Chang TY, Shaw PE, Reynolds LE, McKay TR, Wang HW, Ribeiro PS, Plevin MJ, Lagos D, Lemoine NR, Rajan P, Graham TA, Chelala C, Hodivala-Dilke KM, Spendlove I, Sharp TV. EMBO Mol Med (2018) PMID: 29930174

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

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 TV. Nat 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 TV. Proc 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 variety of basic cancer cell biology and translation research themes ranging from DNA repair and genome stability, RNA biology including localisation, splicing and microRNA-silencing, to cancer cell metabolism/hypoxia, pre-clinical imaging, drug development and computational bioinformatics.

Our work focuses on basic biology, the identification of biomarkers for cancer diagnosis and treatment, and the development of new targeted therapies, including immune-oncology and oncolytic virotherapy.

External Activities

Editorial Board Membership:

  • Nature Press: Scientific Reports

Reviewer for the following Journals:

  • Oncogene
  • RNA
  • Nature Press
  • Journal of Molecular Medicine
  • PLoS Press
  • Nucleic Acids Research

Reviewer for the following Funding Bodies:

  • MRC
  • BBSRC
  • CRUK
  • British Lung Foundation
  • L’OREAL-UNESCO for Women in Science
  • Worldwide Cancer Research
  • The Netherlands Organisation for Scientific Research

Member of:

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

See other researchers working on:

Cancer and Ageing Cell Signalling Lung and Mesothelioma
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