Cancer is a heterogeneous disease with unique genomic and phenotypic features that differ between individual patients and among different regions within the same tumour. In recent years, large-scale genomic studies and new next-generation sequencing technologies have uncovered details about tumour heterogeneity, with significant implications for the choice of specific molecular biomarkers and clinical decision-making.
Oral squamous cell carcinoma (OSCC) is highly heterogeneous at both the genetic and phenotypic levels and despite the advances in treatment, the incidence is rising and the 5-year survival rate, which has not improved in decades, is only 50%. The nature of the mutations and when they are acquired, as well as the effects of those mutations on the underlying stroma and immune cell infiltrate, are one of the primordial reasons for its heterogeneity affecting the course of the disease and ultimately the response to treatments. Furthermore, various immune cells have been suggested as prognostic markers for cancer patients.
The aim of this project it to understand the molecular and cellular heterogeneity in OSCC: (1) using next generation sequencing we will identify genomic alterations of key genes and pathways that can be targeted therapeutically, and (2) using high-throughput imaging and machine learning we will assess the prognostic value of tissue-infiltrating immune cells in OSCCs.
The findings from this study will have important implications in the advancement our knowledge on the role of immune cells in oral cancer progression and will provide clues about future biomarkers for cancer therapy.
Dr Sequeira’s lab is particularly interested in dissecting the molecular and cellular mechanisms involved in oral cancer formation and in understanding the regenerative potential of the oral mucosa. Dr Sequeira and her team aim to combine experimental and theoretical approaches including cutting-edge imaging with computational modelling to map the cellular interactions, and transcriptomics to uncover intrinsic and extrinsic signals during oral wound healing and tumour formation. This research has broad translational applications: the identification of the microenvironment signatures will offer an exciting strategy to accelerate wound healing after tumour resection during oral cancer surgical treatment and to improve the quality of life for cancer patients.
How to apply:
For more information regarding the project, please contact Inês Sequeira (https://www.qmul.ac.uk/dentistry/people/profiles/sequeira.html
Applications should be submitted through the Queen Mary application system. Please indicate the project title and supervisor in the ‘Research Degree Programmes - Additional Questions’ section of the application.
Alongside the application form, please send the following supporting documents:
• Curriculum Vitae (CV)
• Copies of your degree certificates with transcripts
• Proof of English language ability for overseas applicants from non-English speaking countries
• A one-side A4 statement of purpose. This should set out your previous academic or other experience relevant to the proposed research; why you wish to undertake this research at QMUL; your previous research or professional training and what further training you think you will need to complete a PhD; and what ethical issues you will need to consider in undertaking this research.
• Two references. At least one reference must be from an academic referee who is in a position to comment on the standard of your academic work and suitability for postgraduate level study. Where appropriate, a second referee can provide comment on your professional experience.
Please contact the PGR Administrator on ([email protected]
) with any queries about the application process.
Sequeira I, Neves JF, Carrero D, Peng Q, Palasz N, Liakath-Ali K, Morgan P, Graham L, Lombardi G, Watt FM (2018). Immunomodulatory role of Keratin 76 in oral and gastric cancer. Nature Communications. doi:10.1038/s41467-018-05872-4
Sequeira I, Watt FM (2019). The role of keratins in modulating carcinogenesis via communication with cells of the immune system. Invited Review for Cell Stress. doi: 10.15698/cst2019.04.184
Joost S, Annusver K, Jacob T, Sun X, Sivan U, Dalessandri T, Sequeira I, Sandberg R, Kasper M. The molecular anatomy of mouse skin during hair growth and rest. BioRxiv doi.org/10.1101/750042.
Weber C, Telerman SB, Sequeira I, Liakath-Ali K, Reimer AS, Arwert EN, Watt FM. (2016). Macrophage Infiltration and Alternative Activation during Wound Healing Promote MEK1-Induced Skin Carcinogenesis. Cancer Research. doi: 10.1158/0008-5472.CAN-14-3676