Professor Tyson V. Sharp
Group Leader
Professor of Cellular and Molecular Biology
Overview
My research is driven by a commitment to unravelling the complexities of cancer biology, with a particular emphasis on the molecular mechanisms that underpin the disease's development and progression. At the heart of my work is the exploration of LIMD1, a protein that plays a pivotal role in cell cycle regulation, tumour suppression, and the cellular response to hypoxia. By integrating studies on molecular virology, immuno-oncology, microRNA biology, and the development of innovative preclinical models, my research aims to identify novel therapeutic targets and strategies to combat cancer. This multidisciplinary approach not only seeks to advance our understanding of cancer but also to translate these findings into meaningful clinical applications, ultimately improving patient outcomes.
Team
Dr Alexander Crozier
Postdoctoral Researcher
Zhen Gao
PhD Student
Dr Paul Grevitt
Postdoctoral Researcher
Yunjing He
PhD Student
Dr Akash Saha
Research Technician
Dr Kunal Shah
Postdoctoral Researcher
Oliver Yuan
PhD Student
Research
 Foxler et al. A HIF-LIMD1 negative feedback mechanism mitigates the pro-tumorigenic effects of hypoxia. EMBO Mol Med (2018) 10, e8304. 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). More recently we have demonstrated the key role LIMD1 has as a scaffold protein in regulating the hypoxic response (how cells sense and respond to low levels of oxygen), through our seminal discovery of LIMD1 binding the PHD2, VHL and HIF proteins (Nature Cell Biology 2012). Furthermore, we have demonstrated that disruption of this complex and its regulation contribute to the development of lung cancer with very poor prognosis (EMBO MM 2018). 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 focused 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 GroupCandidates interested in joining the lab to work in this research area can contact Professor Sharp by sending an email to t.sharp@qmul.ac.uk. Currently positions are only available to self-funded students. Cell videos Video 1: *Click on image for video*  Video 2: *Click on image for video* Video 1: Time lapse fluorescent confocal microscopy of LIMD1-mTan (Red) and DCP2-(GFP)-tagged proteins expressed in a cancer cell. Here we used dual colour fluorescence microscopy to visualize how LIMD1 is able to form a variety of intracellular condensates/phase separations; some of which we have published (PNAS 2010, Cell Reports 2017) are mRNA processing bodies involved in microRNA-mediated gene silencing. Here we see that co-expression with the mRNA de-capping protein 2 (DCP2) produces the formation of a plethora of highly mobile and divers complexity of P-bodies and phase separated condensates. The function of these structure in basic biology and also deregulated signalling in caner biology is a new and exciting area of investigation in our group. Video 2: An old movie (2005) LIMD1-GFP-tagged protein expressed in cancer cell and visualised with standard time lapse fluorescence microscopy. Here we can see the highly dynamic nature of LIMD1 condensates as the migrate throughout the cell cytoplasm and also fuse with each other as they progress toward the nuclear membrane. Understanding the link between phase, motility function and cancer biology is an new area of research within my team. |
Key Publications
- C-terminal tagging impairs AGO2 function. RNA Biol. 2025 Dec;22(1):1-24. PMID: 40698645
- The DNA mismatch repair protein, MSH6 is a novel regulator of PD-L1 expression. Neoplasia. 2025 Sep;67:101207. PMID: 40651337
- Targeted therapy for LIMD1-deficient non-small cell lung cancer subtypes. Cell Death Dis (2021) 12, 1075. PMID: 34764236
- A HIF-LIMD1 negative feedback mechanism mitigates the pro-tumorigenic effects of hypoxia. EMBO Mol Med (2018) PMID: 29930174
- Argonaute Utilization for miRNA Silencing Is Determined by Phosphorylation-Dependent Recruitment of LIM-Domain-Containing Proteins. Cell Rep (2017) 20(1):173-87. PMID: 28683311
Major Funding
- 2026-2027 – Cancer Research Horizons Early Validation Fund, ‘Cancer Research Horizons for precision therapy in LIMD1-Deficient Lung Cancer.’, £74,000
- 2026-2027 – CRUK City of London Centre Development fund, ‘Mapping the metabolic pathways of high-fat diet-induced tumorigenicity and metastasis in triple-negative breast cancer’, £21,309, co-PI with Dr Paul Grevitt
- 2024–2027 – Barts Charity grant, ‘Deciphering the Mechanisms Governing Response to Immune Checkpoint Blockade in BRCA mutant Ovarian Cancer’, £271,675
- 2023–2026 – Prostate Cancer UK Research Innovation Award, ‘Understanding and exploiting the PTEN driven alternative splicing programme in hypoxic prostate tumours’, £275,357
- 2023–2026 – Breast Cancer Now project grant, ‘Defining a new breast cancer tumour suppressor gene’, £242,000
- 2022-2024 – Rosetrees Trust Intermediate Research Project Award, £51,288
- 2022-onwards – BBSRC, ALERT-Equipment bid Award, ‘A confocal microscope for multidisciplinary dynamic studies of complex biological systems’, £390,834, Co-PI
- 2022-2024 – Barts Charity, Grant Seed Award, ‘Development of a new and more disease relevant mouse lung cancer model’, £48,256, PI
- 2021-2024 – BBSRC Project Grant, ‘The Lexicon of miRISC: Deconstructing the functional complexity of the miRNA induced silencing complex’, £633,000
Other Activities
Editorial Board Membership
- Nature Press: Scientific Reports.
- Frontiers in Cell and Developmental Biology (Associate Editor)
- Frontiers in Oncology (Associate Editor)
- Cells (Topic Editor)
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
Biography
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.
Related News
Protein lost in lung cancer reveals hidden layer of gene control
Scientists at Barts Cancer Institute, Queen Mary University of London, have uncovered an important way that cells keep their genes under control. The discovery could help explain one of the earliest molecular changes that occurs during the development of lung cancer. The study, published in Science Advances, reveals that a protein called LIMD1, which is frequently lost in lung cancer, plays a much bigger role in controlling gene activity than scientists previously realised. The findings uncover a previously hidden layer of gene regulation and may provide new insight into how normal cells begin to lose control during the earliest stages of cancer.
Publications 23 July 2026
Driving Discoveries for Tomorrow’s Cancer Care
Today, on World Cancer Day, we’re sharing a new film. Join us as we go behind the scenes at Barts Cancer Institute (BCI), Queen Mary University of London and meet the people who are making progress possible.
Video 4 February 2026
Science and art collide at this year’s Royal Academy’s Summer Exhibition
An artwork by Professor Tyson V. Sharp from Barts Cancer Institute at Queen Mary University of London has been selected for display in Room VIII at the Royal Academy of Art’s prestigious Summer Exhibition.
Engagement 21 June 2022
Investigating new strategies to target lung cancer
Recent research from Barts Cancer Institute (BCI) at Queen Mary University of London has identified a novel therapeutic strategy to target lung cancer tumours that lack the gene LIMD1.
General News 6 December 2021
Tackling the deadliest cancer type
November is Lung Cancer Awareness Month. Lung cancer is one of the main cancer types on which research is focused here at the Barts CRUK Centre.
General News 30 November 2018
Researchers identify new mechanism implicated in lung cancer progression
A new study performed by researchers from BCI led by Dr Tyson Sharp, Lead of the Centre for Molecular Oncology, has identified a novel mechanism implicated in the development of lung adenocarcinoma (the most common type of non-small cell lung cancer), mediated by the loss of a gene called LIMD1.
General News 7 August 2018