Harrison Laboratory

The Harrison Lab is focused on understanding the mechanisms controlling host-microbe interactions at barrier sites such as the skin and the gastrointestinal tract. We study how our resident, or “commensal,” microbes influence the development, education and function of our immune system. The lab investigates the molecular mechanisms of how T and B cell responses to these commensal microbes are mounted and function. The goal is to understand how these immune cells promote barrier tissue integrity and repair, and to understand how this goes awry during disease. For even more information about the Harrison Lab, visit: harrison-lab.org.

Commensal-specific immunity in tissue homeostasis

As humans, we co-exist with a vast ecosystem of microbes that reside at our barrier surfaces, including the skin and gastrointestinal tract. These commensal microbes are critical for our health, providing resistance to pathogenic microbes, aiding digestion and promoting development and education of our immune systems. Much of our understanding and studies of how the immune system functions were learned using models of infection and inflammation. By contrast, the vast majority of host-microbe interactions occur in healthy barrier tissues colonized by commensal microbes. How our immune system recognizes and responds to commensal microbes in poorly understood. The Harrison lab is working to further understand the mechanisms by which immunity to commensal microbes is mounted, and how these commensal-specific T and B cells promote tissue homeostasis and repair, with the goal that these mechanisms may be harnessed for treatment of chronic inflammatory barrier tissue disorders.

Post-transcriptional regulation of tissue resident T cell function

Upon activation, naïve T cells proliferate, differentiate and ultimately adopt a number of distinct fates, including establishment as long-lived tissue resident memory T cells. These tissue resident T cells can act as sentinels of the immune system, able to rapidly respond to tissue injury and reinfection. As yet, how these cells may lay dormant for years, and yet react within minutes of injury remains poorly understood. We are working to understand how tissue resident T cells adopt a poised transcriptional and translational profile that allows rapid and tailored responses to tissue injury, whilst maintaining tight regulation over these potent and toxic effector molecules during homeostasis. The Harrison lab is working to further understand the post-transcriptional mechanisms that allow storage and stability of mRNA for effector cytokines, and the cues that trigger rapid protein translation and release to promote wound healing and tissue repair. The lab is insterested in understanding how dysregulation of these mechanisms may result in aberrant tissue repair or fibrosis in inflammatory tissue disorders.

Genetic regulation of T cell function upon tissue entry

Both skin and the gut represent the first sites of entry to pathogenic microbes, but are also colonized by a number of immunogenic commensal microbes. Additionally, these sites are major anatomical sites for development of inflammatory tissue disorders. Within these highly specialized anatomical sites, we seek to understand how the immune system mounts adaptive immune responses to distinct microbes, and how these differ from pathogenic T cell responses in chronic inflammatory disorders. Using novel tools to track commensal and pathogenic-specific T cells during ongoing infection and inflammation, we seek to understand at a genetic level how T cell trafficking from lymph nodes, through the circulation and into tissues imprints these distinct effector functions. We are working to further understand how the local milieu, including commensal-derived antigens and metabolites, dietary components and tissue-specific factors, educate these responses in health and disease. The goal is to understand how we may target pathogenic and tissue-destructive T cell responses in disease, whilst maintaining immunity to invasive and commensal microbes at these key barrier sites.