Colby Zaph, University of British Columbia

Profile photo of Colby Zaph, expert at University of British Columbia

Associate Professor Pathology and Laboratory Medicine Vancouver, British Columbia colby@brc.ubc.ca Office: (604) 822-7231

Bio/Research

The current research interests of the lab are focused on defining the molecular and cellular mechanisms that regulate immunity and inflammation at mucosal sites. Specifically, I am working with two gastrointestinal (GI) pathogens, the nematode parasite Trichuris muris and the bacterial pathogen ...

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Bio/Research

The current research interests of the lab are focused on defining the molecular and cellular mechanisms that regulate immunity and inflammation at mucosal sites. Specifically, I am working with two gastrointestinal (GI) pathogens, the nematode parasite Trichuris muris and the bacterial pathogen Citrobacter rodentium. These two mucosal pathogens provide unique and powerful tools to dissect the regulatory pathways that govern innate and adaptive immune responses in the gut.

Trichurismuris is a natural GI nematode parasite of mice and provides and immunologically well-defined murine model for human trichuriasis, a disease afflicting approximately 1 billion people worldwide. Infective eggs are ingested orally, releasing larval parasites that reside within syncitial epithelial tunnels in the cecum and large intestine. Chronic infection is promoted by type 1 cytokines such as IL-18 and IFN-g, while type 2 cytokines including IL-4, IL-13 and IL-25 mediate host resistance.

Citrobacter rodentium is a natural Gram-negative bacterial pathogen of mice. Citrobacter enters the host orally, colonizes primarily the cecum and distal colon, and results in attaching/effacing lesions, similar to those observed following infection with enteropathogenic Escherichia coli (EPEC). Infection also results in crypt hyperplasia and goblet cell depletion. Resistance to Citrobacter infection has recently been shown to be associated with production of IL-23 and IL-17.

While the basic immunological mechanisms associated with immunity to Trichuris and Citrobacter are becoming clearer, the cellular and molecular mechanisms that control how these pathogens are recognized by the innate immune system, how CD4+ T cell memory is regulated in the gut, how CD4+ T cells migrate to the large intestine and what the immune effector mechanisms are that mediate expulsion of these infections are unknown.


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