Cancer associated fibroblasts in cutaneous squamous cell cancer: defining the therapeutic potential of their epigenetic and transcriptional regulation

This is an exciting opportunity for a 3-year BCSC Alexandra Carrell funded PhD studentship within the world-renowned William Harvey Research Institute at Barts and The London Medical School and Dentistry (SMD) at Queen Mary University of London (QMUL) in collaboration with King’s College London. Applications are invited from highly motivated graduates with a BSc (First or Upper Second) or MSc (Distinction or Merit) from biological or related sciences. Previous research experience in bioinformatics, molecular biology techniques and cell culture would be an advantage. Applicants should have a high level of proficiency with computer software related to laboratory research, data presentation and statistical evaluation, as well as the ability to organise a varied workload and to work within a team.

Project background:

Cancer associated fibroblasts (CAFs) are a central component of the tumour microenvironment with diverse pro-fibrotic functions that can either promote or inhibit tumour development [1]. CAFs either reside within the tumour margin or infiltrate the tumour mass, and show increased proliferation, migration, connective tissue deposition and secretion of growth factors and other tissue remodelling factors. Recent advances in single cell sequencing technologies have revealed an astonishing functional heterogeneity within this cell population which may be responsible for their opposing effects observed in different tumours [2]. In cutaneous and other squamous cell carcinomas (SCC) CAFs have been shown to be key drivers of malignancy [3], however, the molecular and cellular mechanisms that determine their pathological functions are largely unknown.

Using a novel 3D-culture model we will screen CAFs from primary non-metastasising and metastasising SCC lesions for persistent malignant phenotypes (Objective-1). Next, we will perform state-of-the-art sequencing, combining ATAC-seq and RNA-seq, of identified CAF populations to dissect the epigenetic and transcriptional regulators promoting tumour development which will be validated in human tumours (Objective-2). Identified candidates will be genetically (shRNA and/or overexpression) or chemically (inhibitors and/or activators) manipulated in healthy fibroblasts and CAFs and functionally analysed in our 3D culture model (Objective-3).

Upon completion, this PhD studentship will provide essential new knowledge on the molecular mechanisms maintaining pathological CAF behaviours that will support the development of new CAF-targeted cancer therapies.

Environment and PhD training:

QMUL has an outstanding reputation for its research including in the field of skin cancer biology and training of PhD students. Located in the centre of London, it integrates several world-leading research centres including the William Harvey Research Institute, Barts Cancer Institute and Blizard Institute creating a strong multidisciplinary research environment delivering both high quality basic and translational research. This PhD studentship is part of the Barts Centre for Squamous Cancer (BCSC), a new centre of excellence dedicated to improving detection, treatment, and quality of life for patients with squamous cancer (https://www.qmul.ac.uk/bcsc/). The PhD student will benefit from a state-of-the-art infrastructure including superb imaging, flow cytometry, tissue culture and histology core facilities, with dedicated support staff at QMUL and KCL. The student will be supervised primarily by the first supervisor, but with regular input and support from the second and third supervisors. Both host laboratories are well staffed with both research (PDRAs) and core technical staff who will provide expertise and local training for the PhD student. As well as learning key cell biology techniques, the student will receive bioinformatics training in RNA-seq/ATAC-seq analysis from the Genomics Core facility at QMUL. Students will be supported to attend international and national conferences, e.g., BAD and ESDR annual meeting.

For more information please contact Dr Emanuel Rognoni ([Email Address Removed]) and visit the QMUL website (https://www.qmul.ac.uk/whri/people/academic-staff/items/rognoniemanuel.html).

Applications should be sent directly to QMUL admissions via this link (choosing the category: PhD Full-time William Harvey Research Institute (non-clinical) Semester 3 (April Start)): https://www.qmul.ac.uk/postgraduate/research/subjects/medicine-william-harvey-research-institute.html