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Di Cara Lab

Investigating Peroxisomes in the Immune System

Our Research

The metabolic machinery of the cell and the array of immune defense pathways are highly intertwined. Peroxisomes, essential metabolic organelles that manage cellular lipid and redox turnover, were recently discovered at the nexus of these two systems. We demonstrated that peroxisomes were required for immune cells to phagocytose of pathogens and drive antimicrobial signaling pathways and for the maintenance of enteric immunological homeostasis. 


Our research program aims to define peroxisome-specific requirements during immune challenge. Much of peroxisome biology was explored in single cell systems, due to the severe early developmental interruptions caused by  peroxisome defects in mice and humans. However, employing the vast genetic arsenal of the Drosophila model system allows us to finally explore the tissue-specific peroxisome contributions to immunity.  


Going forward, we aim to understand the role that peroxisomes and peroxisome metabolic products (lipids and reactive species) play in the Drosophila Toll and IMD immune defense pathways (orthologous to the human Toll and TNF innate immune pathways) for the resolution of infection. Defining the roles of peroxisomes in these processes has implications for our understanding of peroxisome metabolic signaling in inflammation, immunodeficiency, cancer and diabetes and opens a new unexplored field of the innate immunity.

Defining How Macrophage Peroxisomes Contribute to Immune Functions.

We demonstrated that peroxisomes have a direct involvement in immune defense, with evidence that phagocytic clearance of pathogens by macrophages and other professional phagocytes is peroxisome-dependent.

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Mapping peroxisome-dependent gene expression networks of the immune response in vivo.

Immune cell activation in response to infection involves a massive change in the gene expression profile. We found that immune cells lacking functional peroxisomes fail to activate key signaling pathways of the antimicrobial immune response during systemic infections. To better understand the global impact peroxisomes have on immune signaling pathways, we will map the peroxisome-dependent gene network during an infection.

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The Peroxisome Role in Mucosal Immunity and Gut Health

In a recent study we found that peroxisomes in the Drosophila gut modulate the autophagy pathway, stress signaling and tissue regeneration to maintain gut epithelial homeostasis, promote gut epithelial renewal, and ultimately influence host–commensal and host–pathogen interactions needed for the survival and development. This demonstrated a key requirement of peroxisome functions in the gut epithelium for the organism health that was previously unknown. We now are investigating the molecular controls behind this requirement and how they impact immunity in human enteric tissues. 

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Image by Christa Dodoo

Lab Team

Scientist in the Lab

Available Positions

Postdoctoral Fellow

Postdoctoral applicants interested in acquiring a background in peroxisome biology, immuno-metabolism and new areas of immunology, we are currently seeking candidates for several projects.

Graduate Students Interested in MSc or PhD Programs

Currently seeking curiosity-driven individuals with an appetite for discovery.

Lab Technician

We are in search of a full or part time technician who is organized, analytical and willing and able to conduct experiments.

Undergraduate Students

We are looking for motivated undergraduate students who are interested in experiential learning or who wish to enroll in an honors research project.

Our Support

The Canadian Institutes of Health Research provides funding support for our research on peroxisomes in immunometabolism.

The Natural Sciences and Engineering Research Council provides support for our research on peroxisome roles in phagocytosis

Research Nova Scotia provides us funding support for our research program.

The Dalhousie Medical Research Foundation provided funding for our startup funds research equipment needs. ​

The Beatrice Hunter Cancer Research Institute provides funding support for our research.

Canadian Foundation for Innovation provided funds for our research equipment through the CFI-JELF.

The IWK Foundation provided establishment funds for our lab.

Canada Research Chairs Suppports Dr. Di Cara, a Tier 2 Chair in Human Immunology and Host Pathogen Interactions.

The Multiple Sclerosis Society of Canada supports our efforts along with Dr. Christopher Powers (U. Alberta), the primary grant holder, to understand of the underlying causes of neruodegenerative disorders. 

The Rare Diseases Network supports our efforts to generate a Drosophila model that will aid our understand of the underlying causes of Roifman syndrome.  

New Frontiers Research Fund supports or research of how changes in the microbiome and diet affect neurodegenerative diseases.

The National Institutes of Health supports our studies along with Dr. Neil Silverman (U. Mass), the primary grant holder, in the Drosophila model to define the regulatory mechanisms in the inflammatory signaling pathways  

Microscope

Contact

Dalhousie University
University Ave, Halifax, NS, Canada

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