Cancer patients often present metastasis at diagnosis, a state where cancer has spread from its original site. Once this complex and still largely mysterious process starts, the cancer becomes much harder to treat. "Many cancer therapies fail because we still have a poor understanding of the cellular mechanisms underlying tumour progression", Dr. Kok Hao Chen points out. "We need to find ways to detect and analyze cancer growth early." "I learned from my clinical colleagues that a tumour is a highly heterogeneous tissue consisting of cancer cells, immune cells, stromal cells (connective tissue cells), and many other components", explains Dr. Chen. "Observing their spatial organisation and complex interactions has been a technical challenge. Current techniques either provide detailed RNA profile of each cells or spatial organisation of a few RNAs, but they can't do both. The MERFISH technique can. It is indeed uniquely suited to address this question". During his graduate study, Dr. Chen and his colleagues developed an innovative state of the art imaging technology, called MERFISH, capable of mapping tissue functions at the cellular level by analyzing hundreds of RNA molecules inside individual cells. Recognizing the need for a detailed cellular map of the tumour microenvironment, Dr. Chen aims to apply the MERFISH technique to analyze tumour samples for his post-doctoral work.
"So far, the spatial organisation of a tumour's microenvironment is kind of a black box and it could vary wildly between patients," Dr. Chen explains. "We don't have a clear picture of how the growing cancer cells interact with the surrounding tissue and how the cells from our body are responding to it. Accurately reading a tumour’s cellular state may help us see critical cues about cell behaviour". Using MERFISH, Dr. Chen and his team aim to dissect both the nature and the organization of exchanges taking place in and around the tumour.
A two-in-one technology to shed light on the mechanisms driving the disease
During his two-year research project, Dr. Chen's objective is to adapt and optimize the MERFISH technique for the study of tumour clinical specimens. Once the technique is established and tested, him and his team will be able to use it to compare the gene expression patterns of different tumour stages and therapeutic outcome. In doing so, they hope to identify spatial patterns to better classify tumours, biomarkers that could more accurately predict the efficacy of existing treatments, or discover new pathways that could be therapeutically targeted.
Using a remarkably multi-disciplinary approach combining bio-informatics, imaging, synthetic biology and clinical oncology, Dr. Chen's project will significantly contribute to a better understanding of the mechanisms involved in tumour growth and metastasis. Making single-cell resolution maps possible, his state-of-the art and innovative imaging technique could also be extended to other diseases.
