Lisa Osborne

Our intestines are home to countless viruses, bacteria, fungi, and worms, which together make up the gut multibiome. Members of this multibiome help to regulate normal functions for our health, such as digestion and immune system development. However, disruptions to the intestinal ecosystem are associated with multiple inflammatory diseases. My research investigates how members of the multibiome interact with each other and the host to coordinate immune responses to viruses. We are also exploring how viral infections, diet, and the gut multibiome can together contribute to the development of multiple sclerosis, with the ultimate goal of informing prevention and therapy.

1. Regulation of antiviral T cells by the intestinal epithelium

In the gut, a single layer of epithelial cells separates the microbiota from underlying cells and tissues. Intestinal epithelial cells relay signals from the microbiota to both resident and distal immune cells, but the importance of these signals in maintaining immune cell function and localization remain incompletely understood. Our work aims to determine how signals from intestinal epithelial cells regulate T cell localization and function following a viral infection. This research will provide a better understanding of how protective immunity to intestinal pathogens is generated, and has implications for the development of vaccines and immunotherapeutics for intestinal inflammation.

2. The role of STAT1 in persistent viral infection

Viral components of the microbiota can contribute to intestinal homeostasis and protection from local inflammation or infection. However, host-derived mechanisms that maintain tolerance to the virome are largely unknown. We are investigating the role of Signal Transducer and Activator of Transcription 1 (STAT1) in maintaining tolerance to a persistent, commensal-like virus, murine norovirus (MNV). These studies will elucidate molecular mechanisms underlying functional outcomes (clearance or persistence) of viral infections.

3. Interrogating the impact of intestinal communities on neuroinflammation and neurodegeneration in a mouse model of Multiple Sclerosis

Multiple sclerosis (MS) affects tens of thousands of Canadians, and age is the most significant risk factor for development of progressive forms of MS. Aging is associated with multiple physiological changes, including the composition of the intestinal microbiota, which has been associated with susceptibility to MS. We are interested in how environmental influences such as age, diet and exposure to helminths influences disease onset, severity and progression. We are particularly interested in identifying how these environmental perturbations can alter the function of intestinal microbial communities and defining the role of these alterations in susceptibility to neuroinflammation and neurodegeneration. A portion of this work is being pursued in tandem with a collaborative national team. Collectively, the goal of these investigations is to define pathways associated with pathogenesis or protection from disease to identify new therapeutic options.