Molecular Immunology Laboratory
Dr Conor Kearney
Systematic identification of novel targets to improve immunotherapies for colorectal cancer.
Immunotherapy has revolutionized the treatment of cancer, with checkpoint blockade therapy showing remarkable efficacy in several cancer subtypes, particularly melanoma. Despite this success, the majority of patients do not respond, for reasons that are not well defined, or acquire resistance after treatment. Furthermore, immunotherapies have proven to be relatively ineffective against some cancer types, including colorectal cancer. Thus, there is an unmet need to unveil novel approaches to boost the response rate and prolong the extent of the benefit in colorectal cancers, among other cancer types. Similarly, despite the success of adoptive cellular therapy (ACT) in the context of haematological malignancies, response rates against solid cancers is poor, likely due to tumor-associated immunosuppression and subsequent T cell dysfunction/exhaustion. Indeed, it is becoming clear that the failure of T cells to elicit a successful and long-term anti-tumor immune response is controlled by transcriptional, epigenetic and post-translational modifications, however, our current understanding of the molecules involved in these processes is poorly understood. Thus, there is urgent need for a systematic and high-throughput approach to identify novel immunotherapy targets in this regard.
We hypothesise that unidentified genes or proteins in T cells can be targeted genetically or pharmacologically to improve T cell-mediated anti-tumor immunity in colorectal cancer.
This project will use a high throughput screening approach involving cutting-edge technology including in vitro and in vivo CRISPR/Cas9 genetic screens, the development of novel, high throughput drug screening platforms and single-cell sequencing technology to identify novel targets to improve T-cell mediated anti-tumor immunity in colorectal cancer.
Some experience in molecular biology techniques, computational biology and/or experimentation involving mice would be beneficial.