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Research in our laboratory focuses on the role of oxidation and other posttranslational modifications in the pathogenesis of inflammatory and thrombotic diseases by incorporating the use of mass spectrometry, proteomics and analytical biochemistry. These studies encompass three primary areas:
MMPs function in homeostatic and repair processes, but dysregulation of MMP activity is implicated in a variety of diseases, including cancer, fibroses and inflammation. Our previous work has demonstrated that hypochlorous acid, a reactive oxygen species generated by neutrophils, regulates MMP activity by oxidizing specific amino residues in the prepeptide (activation) and catalytic domains (inactivation). We are now exploring the molecular mechanisms controlling the oxidative modifications of the proteases and protease inhibitors involved in the tissue reactions to inflammation. Furthermore, we are looking for in vivo evidence that oxidative pathways regulate protease activity during inflammation.
A second major effort in our laboratory centers on the structure and regulation of blood coagulation proteins. We are currently attempting to understand how von Willibrand factor (VWF) structure and function are regulated by changes in its redox state. These studies are in collaboration with Dr. José López’s research group. The long-term goal is to explore the functional consequences of posttranslational modifications (PTMs) in blood coagulation proteins.
It has been reported that the generation of RBC storage lesion is associated with oxidation of the cell during storage, but very little is known about the molecular mechanism. We are currently beginning to apply proteomic approaches to study posttranslational modifications of specific proteins, including hemoglobin and membrane skeletal proteins in red blood cells. Our long-term goal is to understand the role of specific modifications, including oxidation, phosphorylation and glycosylation, on the viability of stored and diseased red blood cells.
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