Research Projects

Chemokines are small proteins involved in various immune responses and interact with class A GPCR receptors. They have the potential to form dimers and high-order oligomers in the presence or absence of GAGs, which facilitate the formation of oligomers, receptor binding, and protect chemokines from degradation. However, recent studies have been limited in understanding the functional and structural aspects of heterodimers, particularly those involved in atherosclerosis. The presence of CXC/CC homo/heterodimers in atherosclerosis has been reported, leading to arterial wall lesions, narrowing of the arterial lumen, and formation of atheromatous plaques. The proposed study aims to decipher the differential structural propensities of mixed heterodimers formed between chemokines involved in atherosclerosis, such as GRO (CXCL1/2/3), CXCL10, and CCL2, and the impact of GAGs on their dimerization efficacy. The study will also explore the functional aspect of these heterodimers, as these chemokines are actively involved in atherosclerosis and contribute to the formation of a tightly interconnected chemokine interactome that drives inflammation in atherosclerosis patients. The project integrates innovative approaches, including engineered chemokines, novel NMR experiments for structure determination and ligand binding, and energetic measurements. The research design aims to identify the chemokine interactome involving CXCL1/2/3/8/10 and CCL2 in a diseased model like atherosclerosis. The goal is to define the basic principles of inflammation-associated chemokines' molecular recognition and formulate inhibitors for chemokine-mediated inflammatory diseases like atherosclerosis.