Research Summary

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.

Projects

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.

Bio

B.Sc. (Hons), University of Victoria
Ph.D., University of British Columbia
Postdoctoral Fellow, University of Pennsylvania, Weill Cornell Medical College
Currently Assistant Professor in the Dept. of Microbiology & Immunology, Director of the UBC Gnotobiotic Facility

Awards

Tier 2 Canada Research Chair in Host-Microbiome Interactions
Edmond J Safra Cancer Research Institute Irvington Postdoctoral Fellowship
Michael Smith Foundation for Health Research Senior Graduate Studentship
NSERC Doctoral Post-Graduate Scholarship
CIHR Strategic Training Program in Transplantation Research
Michael Smith Foundation for Health Research Junior Graduate Studentship

Publications

Full list of publications available on: Google Scholar or  PubMed

Select Publications:

1. Perspectives of People with Multiple Sclerosis About Helminth Immunotherapy. Donkers SJ, Kirkland MC, Charabati M, Osborne LC. International Journal of MS Care. 2020. doi: 10.7224/1537-2073.2019-044. PMID:32123528

2. A critical analysis of helminth immunotherapy in multiple sclerosis. Charabati M, Donkers SJ, Kirkland MC, Osborne LC. Multiple Sclerosis Journal. 2020. doi: 10.1177/1352458519899040. PMID: 31971074

3. Recirculating Intestinal IgA-Producing Cells Regulate Neuroinflammation via IL-10. Rojas OL, Pröbstel AK, Porfilio EA, Wang AA, Charabati M, Sun T, Lee DSW, Galicia G, Ramaglia V, Ward LA, Leung LYT, Najafi G, Khaleghi K, Garcillán B, Li A, Besla R, Naouar I, Cao EY, Chiaranunt P, Burrows K, Robinson HG, Allanach JR, Yam J, Luck H, Campbell DJ, Allman D, Brooks DG, Tomura M, Baumann R, Zamvil SS, Bar-Or A, Horwitz MS, Winer DA, Mortha A, Mackay F, Prat A, Osborne LC, Robbins C, Baranzini SE, Gommerman JL. Cell. 2019. doi: 10.1016/j.cell.2018.11.035. PMID: 30612739

4. The Multibiome: The Intestinal Ecosystem’s Influence on Immune Homeostasis, Health, and Disease. Filyk HA, Osborne LC. EBioMedicine. 2016. doi: 10.1016/j.ebiom.2016.10.007. PMID: 27863931

5. TLR-7 activation enhances IL-22-mediated colonization resistance against vancomycin-resistant enterococcus. Abt MC, Buffie CG, Sušac B, Becattini S, Carter RA, Leiner I, Keith JW, Artis D, Osborne LC, Pamer EG. Science Translational Medicine. 2016. doi: 10.1126/scitranslmed.aad6663. PMID: 26912904

6. IL-33-Dependent Group 2 Innate Lymphoid Cells Promote Cutaneous Wound Healing. Rak GD, Osborne LC, Siracusa MC, Kim BS, Wang K, Bayat A, Artis D, Volk SW. Journal of Investigative Dermatology. 2016. doi: 10.1038/JID.2015.406. PMID: 26802241

7. Emerging functions of amphiregulin in orchestrating immunity, inflammation, and tissue repair. Zaiss DMW, Gause WC, Osborne LC, Artis D. Immunity. 2015. doi: 10.1016/j.immuni.2015.01.020. PMID: 25692699

8. Virus-helminth coinfection reveals a microbiota-independent mechanism of immunomodulation. Osborne LC, Monticelli LA, Nice TJ, Sutherland TE, Siracusa MC, Hepworth MR, Tomov VT, Kobuley D, Tran SV, Bittinger K, Bailey AG, Laughlin AL, Boucher JL, Wherry EJ, Bushman FD, Allen JE, Virgin HW, Artis D. Science. 2014. doi: 10.1126/science.1256942. PMID: 25082704

9. Persistent enteric murine norovirus infection is associated with functionally suboptimal virus-specific CD8 T cell responses. Tomov VT, Osborne LC, Dolfi DV, Sonnenberg GF, Monticelli LA, Mansfield K, Virgin HW, Artis D, Wherry EJ. Journal of Virology. 2013. doi: 10.1128/JVI.03389-12. PMID: 23596300

10. Resistin-like molecule α promotes pathogenic Th17 cell responses and bacterial-induced intestinal inflammation. Osborne LC, Joyce KL, Alenghat T, Sonnenberg GF, Giacomin PR, Du Y, Bergstrom KS, Vallance BA, Nair MG. Journal of Immunology. 2013. doi: 10.4049/jimmunol.1200706. PMID: 23355735

11. Commensal bacteria calibrate the activation threshold of innate antiviral immunity. Abt MC, Osborne LC, Monticelli LA, Doering TA, Alenghat T, Sonnenberg GF, Paley MA, Antenus M, Williams KL, Erikson J, Wherry EJ, Artis D. Immunity. 2012. doi: 10.1016/j.immuni.2012.04.011. PMID: 22705104

Office Phone
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Lab Phone
6048220997