Macrophages are found in nearly every tissue of the body and play a critical role in regulating inflammatory and antimicrobial immune responses as well as tissue remodeling and repair.
Through our research, we seek to answer fundamental questions regarding the role of cellular metabolism in regulating macrophage function across diverse tissue microenvironments. We are particularly interested in understanding how mitochondria regulate antiviral immune responses and how viruses are able to target the mitochondria to escape immune responses.
Much of this work focuses on understanding how alterations in cellular metabolism contribute to chronic macrophage activation and dysfunction in HIV infection. We are currently examining how dysregulated cellular metabolism in brain macrophages contributes to neuroinflammation and the development of HIV associated neurocognitive dysfunction.
PROJECT 1: Evaluating the role of mitochondrial reprogramming in antiviral immune responses
Mitochondria are central regulators of cellular metabolism. These highly dynamic organelles alter their location, structure and internal metabolite flux to adapt to local microenvironments and support immune function. This project seeks to understand how the dynamic modulation of mitochondrial function and the production of mitochondrial metabolites and other bioactive molecules promote and amplify antiviral and inflammatory signaling in response to diverse viral ligands and replicating viruses.
PROJECT 2: Investigating the effects of HIV and antiretroviral therapy on mitochondrial function: Implications for viral replication, cell survival and immune responses.
Antiretroviral therapy (ART) has dramatically changed the face of the HIV epidemic, reducing transmission rates and HIV associated mortality. However, ART does NOT fully restore health. In HIV infected adults, persistent infection drives ongoing inflammation and tissue damage, which over time has been shown to contribute to accelerated aging and the development of non-AIDS associated co-morbidities. Our research aims to characterize how HIV and ART reprogram mitochondrial function in monocytes and macrophages and to evaluate how this reprogramming contributes to ongoing viral replication and inflammation in HIV infected individuals.
PROJECT 3: Understanding how interactions between microbial communities and tissue macrophages contribute to delayed wound healing
Delayed wound healing is a significant issue among ageing individuals and those with chronic diseases such as infection, diabetes/vascular disease, and cancer. In the most severe cases, these delays can result in the formation of non-healing ulcers, which can cause pain, hospitalization, loss of function, and may lead to amputations and/or sepsis. In this project we are interested in understanding how interactions between macrophages and microbial biofilms contributes to chronic inflammation and delayed healing in chronic wounds.