Research in our laboratory focuses on the role of protein oxidation and other post-translational 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:

Metalloproteinases
Metalloproteases function in homeostatic and repair processes, but dysregulation of their activity is implicated in a variety of diseases, including cancer, fibroses, inflammation, and thrombosis. Our previous work has demonstrated that hypochlorous acid, a reactive oxygen species generated by neutrophils, regulates MMP-7 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 with emphasis on oxidative inactivation of ADAMTS13. Furthermore, we are looking for in vivo evidence that oxidative pathways regulate protease activity during inflammation.

Blood Coagulation Proteins
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) and fibrinogen structure and function are regulated by oxidative conditions. These studies are in collaboration with Dr. José López at the Puget Sound Blood Center Research Institute, as well as Investigators at the University of Washington. The long-term goal is to explore the functional consequences of post-translational modifications (PTMs) in blood coagulation proteins and the discovery of biomarkers for related diseases.

Red Blood Cell (RBC) Oxidation and Storage Lesion
It has been reported that the RBC storage lesion is associated with oxidation of the cell during storage, but very little is known about the molecular mechanisms. We are currently applying proteomic approaches to study the role of post-translational modifications to both membrane proteins and hemoglobin in the RBC storage lesion and RBCs from patients. 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.