iPSC (somatic cells reprogrammed to an embryonic-stem-cell-like state) are not only a means of patient relevant disease modelling, but de-differentiation of terminal cells to their primitive precursors often reveal aberrations in tissue development. The aim of this project is to specify these aberrations towards therapeutic exploitation. We have in-house optimised protocols for iPSC reprogramming as well as culturing primary cells [mesenchymal stem cells and their derivatives] from malignant and non-cancerous tissues. We have developed state-of-the-art assays enabling us to directly handle patient-specific samples highlighting the clinical translatability of our studies.
Transcriptomic profiling will characterise a range of different cancer cell lines and relevant primary tissues. Pluripotent transcription factors and epigenetic signatures will be specified in these cells and tissues as a basis for stem-cell re-programming into patient and disease-specific iPSC lines. Secreted cytokine profiling in tractable ex vivo cancer-niche co-cultures will further reveal key signatures towards autocrine and paracrine signalling in malignancy and the cancer-associated microenvironment. Ultimately, this information will be applied towards subsequent optimisation of protocols for genetic engineering of disease and parallel isogenic patient-iPSC lines. iPSC lines thus established will be authenticated through STR profiling and karyotyping and further validated through a range of phenotypic characterisation and functional assays. Gene expression profiling of iPSC-de-differentiation will further identify potential therapeutic targets against oncogenic transcription factors and epigenetic regulators. Thus identified targets and strategies will be taken forwards towards future Phase I trials following functional validation.
The successful applicant will be trained in a breadth of cutting-edge research methodologies including primary cell culture, iPSC technology, cancer drug development and specialist molecular biology techniques. The doctoral training programme will further benefit from the lab’s extensive international collaborations with Newcastle University, UCL, The PMC, The Netherlands and the Wyss Institute at Harvard and links with local, national and international hospitals
Eligibility and How to Apply:
Please note eligibility requirement:
• Academic excellence of the proposed student i.e. 2:1 (or equivalent GPA from non-UK universities [preference for 1st class honours]); or a Masters (preference for Merit or above); or APEL evidence of substantial practitioner achievement.
• Appropriate IELTS score, if required.
• Applicants cannot apply for this funding if currently engaged in Doctoral study at Northumbria or elsewhere.
For further details of how to apply, entry requirements and the application form, see https://www.northumbria.ac.uk/research/postgraduate-research-degrees/how-to-apply/
Please note: Applications should include a covering letter that includes a short summary (500 words max.) of a relevant piece of research that you have previously completed and the reasons you consider yourself suited to the project. Applications that do not include the advert reference (e.g. SF20/…) will not be considered.
Deadline for applications: 1st July for October start, or 1st December for March start
Start Date: October or March
Northumbria University takes pride in, and values, the quality and diversity of our staff. We welcome applications from all members of the community. The University holds an Athena SWAN Bronze award in recognition of our commitment to improving employment practices for the advancement of gender equality.
For enquiries, contact Dr Deepali Pal ([email protected]
1. Pal D, Blair HJ, et al. Long-term in vitro maintenance of clonal abundance and leukaemia-initiating potential in acute lymphoblastic leukaemia. Leukaemia 2016, 30, 1691-1700. Impact factor =12; citations = 18. F1000 prime recommendation obtained.
2. Martinez-Soria N.…Pal D…., Heidenreich O. The Oncogenic Transcription Factor RUNX1/ETO Corrupts Cell Cycle Regulation to Drive Leukemic Transformation. Cancer Cell 2018, 34(4), 626-642.e8.. Impact factor = 23.5. Citations = 12
3. Pal D*, Moad M*, et al. A novel model of urinary tract differentiation, tissue regeneration, and disease: Reprogramming human prostate and bladder cells into induced pluripotent stem cells. European Urology 2013, 64(5), 753-761. Impact factor = 17, citations = 60
4. Weiland, J.; Pal, D.; et al. BCP-ALL blasts are not dependent on CD19 expression for leukaemic maintenance. Leukemia 2016, 30 (9), 1920-3. Impact factor = 12
5. Pal D, et al. Dormancy Stems the Tide of Chemotherapy. Cancer Cell 2016, 30(6), 825-826.