We previously identified NUDT22 as an UDP-glucose hydrolase and an important new player in nucleotide and energy metabolism. Our data suggests that cancer cells have an increased dependency on NUDT22 which is further supported by increased NUDT22 expression in many cancer types and worse overall survival in patients with high NUDT22 expression levels in some cancers.
Lung cancer is one of the most frequently diagnosed cancers and the foremost cause of cancer-related death in the UK (CRUK). Common treatments for lung cancer are either radiotherapy or chemotherapy with platinum drugs or immunotherapy often in combination with a second drug such as the nucleoside analogue gemcitabine. Lower tumour response rate to gemcitabine is however often associated with high expression of ribonucleotide reductase (RRM1) and platinum drugs are known to be subject to acquired cancer cell resistance and can cause substantial systemic side-effects. High expression of pyrimidine metabolism enzymes was further identified as adverse prognostic factors in lung cancer.
To be able to better assess the general sensitivity to chemotherapy of NUDT22 deficient lung cancer cells and to better understand the potential cancer specificity we generated NUDT22 knockout cell lines of lung cancer and normal lung epithelium. 3D spheroid and preclinical models will be used to further assess the clinical potential of targeting NUDT22 in lung cancer.
Aim of this project is to (1) assess the differential response to NUDT22 deficiency in cancer vs non-cancer cell lines (2) identification of biomarkers that differentiate sensitive vs insensitive cell lines by LC-MS (3) development of combination treatment strategies (4) translation of findings into preclinical models.
Candidates must have a first or upper second class honors degree and significant research experience.
How to apply:
Please complete a University Postgraduate Research Application form available here: www.shef.ac.uk/postgraduate/research/apply
Please clearly state the prospective main supervisor in the respective box and select 'Oncology & Metabolism' as the department.
Interested candidates should in the first instance contact:
Dr Patrick Herr ([Email Address Removed])