Research Interests:
Immune function is not only supported by, but is dependent on, metabolic reprogramming. This reprogramming is required to meet the bioenergetic and biosynthetic demands of the cells and to regulate gene expression, signal transduction and epigenetic profiles. By altering cellular metabolism, it may be possible to shape and fine tune immune function. Understanding these mechanisms has important implications for the design of more efficacious vaccines, anti-microbial drugs and other immunotherapies for both humans and other vertebrates.
The Cassol lab is dedicated to elucidating the role of metabolic processes in regulating macrophage function. We study macrophages because these cells play a central role in regulating inflammation, host defense and homeostatic functions including tissue remodeling and repair. Dysfunction of these cells has been linked to the pathogenesis of infectious and non-infectious disease.
Project Descriptions:
Regulation of Type I Interferon Responses in Macrophages
Type I IFNs play a seminal role in anti-viral, anti-bacterial, anti-parasitic and anti-tumour responses and they act as crucial regulators of innate and adaptive immune responses. In contrast to these beneficial effects, chronic or sustained IFN responses have been linked to tissue damage and immunosuppression. The mechanisms regulating type I IFN responses are multifactorial and include the induction of negative regulators and the expression of microRNAs. Recent studies suggest cellular metabolism also plays a central role in regulating these responses. However, these processes remain poorly characterized.
Ongoing projects:
- Systematic characterization of metabolic profiles associated with type I IFN responses
- Role of type I IFN in metabolic regulation of TLR responses
- Understanding how aging changes affects type I IFN responses in mice and humans
Collaborators:
Dr. William Willmore, Associate Professor, Institute of Biochemistry, Carleton University
Dr. Alfonso Abizaid, Professor, Department of Neuroscience, Carleton University
Contribution of Metabolic Reprogramming to the Development of Innate Immune Memory
Classical immunological memory refers to the ability of the adaptive immune system to rapidly respond to, and mount, augmented immune responses against subsequent exposures to pathogens. Until recently, it was assumed that only adaptive immune cells possessed the capacity for memory. However, mammalian innate cells also can be functionally reprogrammed by past encounters. These exposures alter the cell’s responsiveness to subsequent stimuli and can induce long-term hyper-inflammatory or hypo-inflammatory states through metabolic and epigenetic reprogramming, collectively termed “innate immune memory”. We have only started defining the role of innate immune memory in contributes to health and disease.
Ongoing projects:
- Systematic characterization of metabolic processes associated with the development of innate immune tolerance (hypo-inflammatory) and training (hyper-inflammatory)
- Examining the role of type I and type II IFNs in innate immune memory
- Studying the role of innate immune training (hyper-inflammatory) in HIV associated cardiovascular disease
Collaborators:
Dr. Ashok Kumar, Principal Investigator and Senior Scientist, Research Institute, CHEO
Dr. Paul MacPherson, Scientist, Chronic Disease Program, Ottawa Hospital Research Institute
Dr. Girish Dwivedi, Cardiologist, University of Ottawa Heart Institute
Metabolic reprogramming of monocytes and macrophages in HIV infection
Viruses including HIV manipulate metabolism of infected cells to meet their structural and functional requirements. Conversely, metabolic reprogramming facilitates cellular activation and contributes to antiviral immune responses. Recent studies have shown that altered glucose metabolism and redox potential of T cells and monocytes contribute to HIV pathogenesis. However, these changes have not been systematically characterized in vitro and in vivo.
Ongoing projects:
- Characterization of the effects of HIV infection on metabolic reprogramming in macrophages
- Examining relationships between the microbiome and innate immune function in HIV-infected children and HIV-exposed but uninfected children
Collaborators:
Dr. Ashok Kumar, Principal Investigator and Senior Scientist, Research Institute, CHEO
Dr. Kristin Connor, Assistant Professor, Department of Health Sciences, Carleton University
Dr. Theresa Rossouw, Associate Professor, Department of Immunology, University of Pretoria
Dr. Ute Feucht, Paediatrician and Lecturer, Department of Paediatrics and Child Health, University of Pretoria