Jeff Dong

Research Summary

Tissue resident macrophages are primordial innate immune cells that help maintain homeostasis and are one of the first responders to infection and injury. Microglia are tissue resident macrophages of the central nervous system (CNS) and they are predominant immune cells that populate the brain and spinal cord. In addition to performing custodial functions, microglia quickly react against injury and accumulate to pathological sites, such as multiple sclerosis (MS) lesions. Our lab focuses on studying how microglia regulate inflammation, repair, and fibrosis in the CNS, especially during multiple sclerosis.

Oxidized phosphatidylcholines (OxPCs) form when free radicals released during inflammation or tissue injury cause normal phosphatidylcholine found in cell membrane or in myelin sheaths to undergo peroxidation. OxPCs are inflammatory, cytotoxic, and are implicated to promote tissue pathology in multiple diseases such as lung fibrosis, fatty liver disease, atherosclerosis, and MS. Macrophages like microglia are phagocytic cells capable of scavenging OxPCs through cell surface scavenger receptors. By studying the OxPCs binding and signaling mechanisms in macrophages and microglia, our lab aims to identify new therapeutics that could be utilized to improve OxPC elimination during injury and disease.  

Ongoing Projects

1. Understanding OxPCs as novel mediators of chronic neurodegeneration and progressive MS.

OxPCs are byproducts of oxidative stress which are increased in acute and chronic MS brain lesions. Yet, how OxPCs contribute to chronic damage in the brain and spinal cord during progressive MS remain mostly unknown. We aim to determine how OxPCs propagate inflammation and chronic injury in the aging brain and spinal cord white matter and grey matter, and to identify new therapeutic strategies to help treat progressive MS.

2. Understanding how macrophages respond to OxPCs.

Phosphatidylcholines (PCs) are major constituents of the cell membrane that separates DNA and other cellular structures from the outside environment. Like all other molecules involved in normal biological processes, PCs are constantly degraded and recycled. However, when oxidative stress occurs, such as during inflammation, PCs can be converted into OxPCs. Abnormal accumulation of OxPCs can cause cell death and propagate excessive inflammation. Thus, organisms need a way to eliminate OxPCs, but these mechanisms are not well understood. In this project, we aim to understand the how tissue resident macrophages use cell surface scavenger receptors such as TREM2 to neutralize OxPCs during inflammation.

3. Determining how long-term exercise modify the resilience of the central nervous system against chronic neurodegeneration and progressive MS.

Exercise is emerging as an intervention for promoting regeneration and remyelination in MS. Since exercise also has potential anti-aging and antioxidative effects, our objective is to test the ability of long-term exercise to neutralize oxidative stress and to help reduce pathology in chronic MS lesions. By identifying the neuroprotective mechanisms induced by long-term exercise, it may be feasible to therapeutically activate the protective benefits conferred by exercise to help people with limited mobility.

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