Dissecting Cancer Cell Heterogeneity and Immune Niches in Colorectal Cancer Liver Metastasis Using Spatial Multi-omics
Supervisors: Dr Peter Wan, Dr Kerry Fisher, Alex Gordon-Weeks
Project Overview
Colorectal cancer liver metastasis (CRLM) represents the major cause of mortality in colorectal cancer and remains a critical clinical challenge. This project will use a multi-omics approach to generate a high-resolution map of CRLM, integrating spatial transcriptomics to capture gene expression profiles and multiplex imaging to provide phenotypic data. Computational integration of these datasets will allow systematic characterisation of tumour heterogeneity and immune organisation within the metastatic microenvironment. The project has two major objectives. First, it will define the heterogeneity of cancer cell populations within CRLM. Increasing evidence suggests that metastatic tumours are not homogeneous but consist of diverse cancer cell populations with distinct functions. These may include proliferative, invasive, metabolically specialised, and therapy-resistant subsets, each contributing differently to tumour progression and clinical outcome. Understanding how these subpopulations are spatially organised and how they interact with the surrounding microenvironment is essential to developing more effective therapeutic strategies. Second, the project will investigate the organisation and role of tertiary lymphoid structures (TLS), organised aggregates of immune cells associated with anti-tumour responses. It will examine whether TLS in CRLM differ in composition or function compared to those in adjacent non-tumour liver tissue, and assess how their spatial proximity to different cancer cell subtypes influences immune surveillance and tumour evasion. This is a highly computational project, offering advanced training in spatial multi-omics data analysis and integration, while maintaining a translational perspective by linking molecular and cellular signatures to tissue context in metastatic disease. Working within a multidisciplinary environment that includes close collaboration with clinicians and translational research teams, you will also gain exposure to clinical material and the opportunity to see how computational discoveries can be developed into strategies with therapeutic potential.
References
Wu, Y., Yang, S., Ma, J., Chen, Z., Song, G., Rao, D., Cheng, Y., Huang, S., Liu, Y., Jiang, S. and Liu, J., 2022. Spatiotemporal immune landscape of colorectal cancer liver metastasis at single-cell level. Cancer discovery, 12(1), pp.134-153.