Research Projects

Monocytes, a subset of white blood cells, are derived from bone marrow and differentiate into macrophages and dendritic cells (DCs), which are healing messengers during inflammation. The differentiation process is regulated by regulatory chemokine proteins called monocyte chemoattractant proteins (MCP). Once out of the bone marrow, monocytes differentiate into proinflammatory and anti-inflammatory subsets based on the expression of G-protein coupled receptors (GPCRs) CCR2 and CX3CR. The proinflammatory subset is found in the circulation and has significant effects on various diseases. MCP chemokines belong to the CC chemokine family and consist of four members: CCL2, CCL7, CCL8, and CCL13. The receptor-chemokine interactions are guided by a gradient of glycosaminoglycans (GAGs) and post-translational modifications (PTMs). The four MCP chemokines exhibit numerous immune activities despite sharing the same structural architecture. The current project aims to study the structural details of important monocyte chemoattractant protein MCP-1, their differential binding characteristics, and the regulatory role of receptor sulfation on binding. The project will also examine molecular interactions with cell surface glycosaminoglycans to assess stability and oligomerization patterns. The project will use an integrated molecular approach, including biophysical, biochemical, and cell-based techniques. The outcome will enhance our understanding of chemokine-receptor-GAG interactions and provide novel class of SMIGs for regulating monocyte infiltration-dependent tissue damage during infectious and inflammatory responses.