About the Project
This is a 4-year PhD studentship funded by The Azima Foundation, which covers tuition fees at the UK rate and a stipend of £21,000 per year. The start date for this studentship is September 2021.
Gastric cancer remains a major cause causing significant mortality. In earlier stages where the cancer has not spread (metastasised), surgery, often combined with preoperative chemotherapy, is the most effective treatment. Progress in treating more advanced gastric cancer has been limited although in recent years there have been advances in drug and antibody therapies. However, although this has resulted in improvements in survival this has been modest and effective treatment of this cancer remains a major challenge. An important discovery was that HER2 is overexpressed in around 20% of gastric cancer patients. HER2 has been widely studied in breast cancer where antibodies targeting this protein (notably trastuzumab/Herceptin) are a mainstay of treatment in patients whose cancers overexpress the protein. An important study in patients with advanced gastric cancer (the TOGA trial), showed that addition of Herceptin to standard chemotherapy could improve survival. Additionally, recent clinical trials using a powerful drug linked to the HER2 antibody known as an antibody drug conjugate (ADC), was able to produce excellent results in treatment of this cancer. In this study, the drug was linked to a chemotherapy drug which damages the DNA of the cancer cell. There is great interest in testing of various ADC’s in gastric cancer.
Both of these areas, HER2 and effects of drugs on cancer cells, have been major interests of our research work for some years. We have studied how HER2 (and the related protein HER1 or EGFR) interacts with specific types of chemotherapy agents. Our team would lead this proposal and supervise the studentship. This consists of Professor Daniel Hochhauser (Kathleen Ferrier Professor of Medical Oncology, UCL) a medical oncologist with a specialist focus in this area and Co-Director of the CRUK DNA-Drug Interactions Research Group with Professor John Hartley (Professor of Cancer Studies, UCL) an international authority in drug targeting and Professor Clare Futter (Professor of Cell Biology, UCL) who is an expert in cell biology. Additionally we will cooperate closely with Professor George Hanna (Head of the Division of Surgery at Imperial College).
The questions we seek to answer with this studentship proposal are
- How does HER2 targeting affect chemotherapy? We will investigate different classes of drugs producing different types of DNA damage to determine which are the optimal combinations. Importantly these studies will be carried out using models derived from actual patient tumours (so-called organoids) with which we have specialist expert support
- What is the cellular fate of HER2 following drug induced stress? This is important in determining optimal strategies of these combinations. HER2 is internalised within the cell following drug treatment and we would investigate as to how this affects the response to treatment and whether it is a factor in drug resistance.
- How does chemotherapy affect HER2 expression? We will study this using cancer models but also, importantly, examining the archival material from patients with gastric cancer who have undergone surgery. This will provide additional important clues as to how HER2 expression could affect response to treatment .
More information about the research project is available on request from Professor Daniel Hochhauser [Email Address Removed]
- Minimum upper second class Honours Degree in natural sciences, biomedical science and engineering, tissue engineering or related discipline, or an overseas qualification of an equivalent standard.
- Preliminary knowledge of research techniques.
- Evidence of motivation for and understanding of the proposed area of study.
- Ability to develop understanding of complex problems and apply in-depth knowledge to address them.
- Potential to develop expertise in new areas of the subject.
- Potential for innovation and initiative, and evidence of an ability to work independently.
- Effective communication skills in both written and spoken English.
- Relevant laboratory research experience.
Duties and Responsibilities
- To apply highly specialist scientific skills and expertise to lead in the delivery of high- quality research and the preparation of high-impact research publications.
- To keep abreast of current developments in this research area.
- To report research progress to the supervisory team, the Cancer Institute, and at scientific conferences and meetings.
- To work with other scientists within the Song, and Mittnacht teams as necessary.
- To work safely by adhering to all University policies and practices, including preparing and following laboratory risk assessments, and complying with Health and Safety policies, ethical approval processes and Human Tissue Act guidelines.
Analytical and Judgement Skills
- To demonstrate high-level of technical and analytical skill to resolve complex problems, requiring analysis, interpretation and expert judgement to find the most appropriate solutions.
- To identify, interpret and integrate information from a wide variety of sources, and critically evaluate the quality and assumptions of these data.
- To show initiative and the ability to make decisions in areas where no previous work has been undertaken.
- To show awareness of your own developmental needs and undertake appropriate training where appropriate.
- To comply with professional codes of conduct.
The UCL Cancer Institute is dedicated to consolidate cancer research at UCL and to promote links with our partner teaching hospitals, in order to support excellence in basic and translational cancer studies. The Institute draws together talented scientists working together to translate research discoveries into developing better, more effective therapies for cancer patients. It holds Cancer Research UK and Experimental Cancer Medicine Centre of excellence status, housing approximately 580 staff, including 120 PhD and MD (Res) students, and 40 MSc students. Research is supported through state-of-the-art platform facilities including the Genomics Facility supporting next generation sequencing, including single cell resolved technologies; a dedicated bioinformatics unit; the Proteomics Facility, Imaging and Cell Sorting (supporting automated, confocal and time-lapsed microscopy, MoFlo and Flow Cytometrie); the Pathology Suite (supporting laser capture microdissection, tissue arrays and immune-histology services), the Experimental Imaging unit and Transgenesis services.
Closing date: 31 May 2021 17:00 (GMT)
Based on your current searches we recommend the following search filters.
Based on your current search criteria we thought you might be interested in these.