My research
Resident T cell immunity to infection
Barrier tissues like the skin form a first line of defence against invading microbes. While immune cells known as T cells were traditionally thought to migrate through the bloodstream in search of pathogens, we now know that specialised subsets of T cells reside permanently in peripheral and barrier organs without circulating in the blood. Our prior research has shown that these tissue-resident memory T cells can proliferate and self-renew when they encounter viruses, allowing them to persist long-term in tissues like the skin after an infection resolves. I am continuing to explore how protective antiviral tissue-resident memory T cell responses are generated throughout the body and how these cells function to protect us from infections using a variety of cutting-edge techniques including CRISPR-Cas9 gene editing technologies and high-dimensional flow cytometry.
Resident T cell immunity against cancer
The immune system is critical to protect against the development and spread of cancer. Immune cells can halt tumour progression by destroying cancerous cells or by suppressing their growth in a process termed ‘cancer-immune equilibrium’. By combining a novel pre-clinical melanoma model and sophisticated in vivo imaging approaches, our work showed that tissue-resident memory T cells are critical to enforce cancer-immune equilibrium, and therefore to prevent melanoma outgrowth in the skin. These findings have provided strong impetus to explore tissue-resident T cells for cancer therapy. To this end, I am currently investigating how tissue-resident memory T cell development and function can be boosted in solid cancers and whether doing so can improve the efficacy of cell-based immunotherapies including Chimeric Antigen Receptor (CAR) T cell therapy.
Resident T cell heterogeneity
Our group has shown that tissue-resident memory T cells are highly protective against infection and cancer but our understanding of how these cells develop remains incomplete. Tissue-resident T cell populations in organs like the skin are highly heterogeneous - while some resident T cells fight infections and cancer, others are implicated in generating and promoting autoimmunity. I am currently investigating how molecular factors and environmental cues like cytokines coordinate diversity in the tissue-resident memory T cell pool by applying bacterial and viral modes of infection in gene-deficient models. Understanding the factors that contribute to tissue-resident memory T cell heterogeneity will aid in the design of targeted therapies that can promote local immune protection against infection and cancer and better treat autoimmunity.