Cai Group: Metabolic and inflammatory crosstalk in the tumour microenvironment

About the Research

Our group is interested in investigating the complex interactions between stromal cells and tumours, which play a crucial role in the immune response and contribute to tumour growth. We aim to understand the mechanisms of this crosstalk, which promotes cancer cell invasiveness, and resistance to chemotherapy and immunotherapy.

Through international multicentre clinical trials on adjuvant chemotherapy for colorectal cancer (CRC), we have built a biorepository of approximately 4,000 tissue samples. Our research has shown that a high ratio of stroma to tumour and elevated expression of stromal cell gene signatures are correlated with advanced disease stages and poor prognosis in CRC.

However, how stromal cell and CRC interactions fuel tumour growth, increase invasiveness, and cause therapy resistance remain unclear. Our team investigates the altered metabolites and inflammatory factors that mediate this crosstalk, with a focus on oncometabolism to uncover changes in immune checkpoints.

This study will utilise advanced ‘omics’ approaches based on RNA sequencing, proteomics and metabolomics analysis. Spatial mapping technologies will also be employed to understand the complexities of tumour stromal cells, particularly immune cells, in CRC tissue samples. Genetic manipulation through genome editing will be used to validate key pathways and molecules involved in stromal-tumour cell interactions. This study will lead to identify biomarkers that predict the efficacy of conventional and immunotherapies and to develop a new class of small molecule inhibitors for CRC.

The study will encompass in cell cocultures, organ-on-chip, animal models and patient-derived tissue explants, with findings to be validated in CRC patient samples.

Training Opportunities

The student will acquire expertise in a wide range of state-of-the-art organ-on-chip, patient-derived tissue explants, molecular and cell biological techniques, and bioinformatics analysis; finally providing an excellent foundation for a research career.  Formalised training and assessment of each technique by our members of the laboratory as appropriate. Our laboratory has clearly defined protocols to support training in specific experimental techniques. Standard operating procedures are regularly updated to ensure that methods are optimal.

Students are encouraged to attend the MRC Weatherall Institute of Molecular Medicine DPhil Course, which takes place in the autumn of their first year. Running over several days, this course helps students to develop basic research and presentation skills, as well as introducing them to a wide range of scientific techniques and principles, ensuring that students have the opportunity to build a broad-based understanding of differing research methodologies.

Generic skills training is offered through the Medical Sciences Division's Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence, and impact. Students are actively encouraged to take advantage of the training opportunities available to them.

As well as the specific training detailed above, students will have access to a wide range of seminars and training opportunities through the many research institutes and centres based in Oxford.

The Department has a successful mentoring scheme, open to graduate students, which provides an additional possible channel for personal and professional development outside the regular supervisory framework. We hold an Athena SWAN Silver Award in recognition of our efforts to build a happy and rewarding environment where all staff and students are supported to achieve their full potential.

Additional supervisors

Publications