CRUK 4 Year PhD Studentship – Autumn 2022 – Cancer Biomarker Centre

Project Title “Defining Mechanisms of Small Cell Lung Cancer Metastasis”
Group Leader Caroline Dive CBE
Research Group Cancer Biomarker Centre

Metastases are the predominant cause of cancer-related deaths. Small Cell Lung Cancer (SCLC), is an aggressive neuroendocrine (NE) tumour, representing ~13% of all lung cancers and is the 6th highest cause of cancer-related deaths worldwide. SCLC is one of the most metastatic cancers (>80% patients present with metastatic disease) with common sites including liver and brain, which are clinically challenging and remain incurable. Until now, lack of robust patient-derived preclinical models and a paucity of SCLC biopsies hampered molecular studies of SCLC metastasis. Our lab developed >60 CTC-derived patient explant models (CDX) in immunodeficient mice which are faithful models of the donor’s disease. Using our newly developed SCLC in vivo resection protocol, multiple subcutaneously implanted then resected CDX models routinely and spontaneously metastasise to multiple organs with similar tropism to that observed in SCLC patients, including brain and liver. This project will involve transcriptomic profiling of liver and brain-metastaic tumours from these mice, comparing single cell data from the mouse SCLC CTCs in order to define the molecular components responsible for liver- and brain-specific organ tropism and also employ spatial profiling (combined transcriptomic and protein-expression analysis) to understand the molecular features enabling metastatic colonisation of these organs. Functional validation of candidates will follow via their in vitro and in vivo manipulation using knockdown/over expression and CRISPR tools and pharmacological manipulation, with the ultimate aim to define their role in clincal specimens and identify novel therapeutic vulnerabilities to benefit SCLC patients in the future.

Registration and graduation will be affiliated to the University of Manchester.
University of Manchester entry September 2022.
Successful applicants will receive a non-taxable annual stipend (living allowance) of £19,000 (GBP) per annum and funding to cover University tuition & bench fees for the 4 years.

Our PhD Studentships are open to applicants from all nationalities.

You can find further information, entry criteria and details on how to apply online at https://www.cruk.manchester.ac.uk/Education/PhD-2022-Apply

Closing date: Friday 22 April 2022 @ 1700 hrs GMT.
Interview date: Friday 27 May 2022.

We plan to hold in-person interviews on site, Alderley Park, Cheshire, UK however, we will take into consideration any change in circumstances at the time to ensure the safety of all concerned and in amending the interview format to virtual.