AG Asif: Clinical Proteomics & Artificial Intelligence Group (CPAIG)

Functional endothelium is responsible for maintaining a balance between vasodilation and vasoconstriction, between inhibition and stimulation of cell proliferation and migration, and between thrombogenesis and fibrinolysis. The functional impairment of endothelium breaks this balance causing damage to the arterial wall. The CPAIG investigates the underlying mechanism of endothelial dysfunction (ED) and its contribution to the development of cardiovascular diseases. The CPAIG has long-standing expertise in the field of clinical proteomics and mass spectrometry for the quantitative and qualitative differential protein profiling, protein-protein interactions, DNA-Protein-interactions, drug protein targets and characterization of post-translational modifications. We utilize omics approaches to broaden our understanding of the mechanism behind the disease progression and investigating the new therapeutic options.

Inflammation, Tight-Junctions and Endothelial Dysfunction

Bromodomain Protein 4 (BRD4), binds multiple promoters as well as intergenic regions, particularly enhancer sequences. The BRD4 inhibition could block NF-kB-mediated super-enhancer formation to help treat inflammation and atherosclerosis. We seek to understand the role of BRD4 isoforms in endothelial dysfunction and how BRD4 inhibition could rescue the endothelium integrity during inflammation. Furthermore, using an endothelial cells (HUVECs) model, we investigate the influence of inflammation on endothelial monolayer tight junctions and the role played by the BRD4 inhibition in preserving its integrity.

Laminar- / Oscillating-Shear Stress and Endothelial Dysfunction

The level of fluid shear stress (FSS) acting on endothelial cells is higher in arterial vessels compared to venous vessels. The nature of FSS experienced by endothelial cells is a function of blood flow patterns generated by the cardiac cycle. We subject the human umbilical vein endothelial cells (HUVEC) to shear forces, as prevalent in vessels, using a special apparatus for both oscillatory and laminar shear stress to mimic a physiological situation. The cellular models are used to broaden our understanding of the influence of age and inflammation in the progression of atherosclerosis.