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  • Shijie Cai

about the research

The primary focus of our lab is to study the crosstalk between stromal cells and tumours, which significantly influences tumour development. We also investigate the mechanisms that promote cancer cell metastasis and resistance to target therapy in cancers.

Malignant pleural effusion (MPE) commonly occurs in lung and breast cancers, as well as lymphoma. MPE formation is primarily due to the invasion of metastatic cancer cells into the thoracic pleural cavity, owing to their anatomic proximity. Most patients with MPE experience a worse clinical outcome, with only less than 25% of them survive > 5 years after diagnosis, particularly in cases of lung cancer.

The cellular components of MPE are diverse, including cancer epithelial cells, inflammatory cells (such as lymphocytes, macrophages, and dendritic cells), and cancer-associated fibroblasts (CAFs). Notably, a higher proportion of double positive cancer cell and CAF clusters in MPE is associated with a worse prognosis for lung cancer patients. Furthermore, cancer cells that cluster with CAFs tend to be more invasive and resistant to chemotherapy or targeted therapy. 

CAFs in the vicinity of the malignant lesions actively support cancer cell proliferation, angiogenesis and invasiveness. It is worth noting that CAFs are dynamic components that can arise from various cell types, including resident cells within the tumour tissue and even endothelial cells. Therefore, investigating the cellular origin of CAFs and the mechanisms driving CAF differentiation may facilitate early detection of metastatic cancer cells and the development of targeted therapies.

The primary aims of this project are as follows:

(1) Investigate endothelial cells as an origin of CAFs in response to cytokine stimulation and inflammatory cell infiltration.

(2) Study how tumour-associated endothelial cells lose some of their markers and acquire mesenchymal-like features.

(3) Determine the mechanisms underlying the transition that confers therapy resistance to cancer cells.

We will analyse alterations in gene and protein expression profiles using molecular and cell biology techniques. Single-cell sequencing will be employed to cluster CAF heterogeneity. Genetic manipulation will be performed to evaluate key pathways and molecules that regulate endothelial cell to mesenchymal transition (EndMT).

The validation of molecules that drive EndMT will be carried out in MPE samples from lung cancer patients. All these studies will encompass in cell cultures, organ-on-chip, animal models and human tumour tissue samples.


Additional supervision may be provided by Professor David Kerr and Professor Holm Uhlig.

training opportunities

The student will acquire expertise in a wide range of state-of-the-art organ-on-chip, 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 supervision will be provided by Professor David Kerr



Wang et al. Cancer Res. 2023 Oct 13;83(20):3400-3413.


Wang et al. eLife.


Zhang et al. Lancet Oncol. 2021 Aug;22(8):e358-e368.


Chen et al. Oncotarget. 2016 Feb 23; 7(8): 9353–9367.


Chen et al. Am J Pathol. 2010 Nov; 177(5): 2671–2680.