Education and Training:

B.S, Chemistry, Zhejiang University, Hangzhou, P.R. China (1982)

M.S.,  Chemistry, Zhejiang University, Hangzhou, P.R. China (1988)

Ph.D, Chemistry, Zhejiang University, Hangzhou, P.R. China (1988)

Visiting Scientist, Washington University School of Medicine,
St. Louis, MO (1999-2001)

CURRENT RESEARCH INTERESTS

Protein oxidation and posttranslational modification, mass spectrometry, inflammation, oxidative stress, von Willebrand factor, red blood cell.

RESEARCH DESCRIPTION

Research in Dr. Fu's lab 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.  Currently, there are three specific areas: on three areas:

Matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs). 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.

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 Willebrand factor (vWF) structure and function are regulated by changes in its redox state. These studies are in collaboration with Dr. Jose Lopez' research group. The long-term goals is to explore the functional consequences of posttranslational modifications (PTMs) in blood coagulation proteins.

Red blood cell (RBC) storage lesion. 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.

SELECTED PUBLICATIONS

Fu X, Kassim SY, Parks WC, Heinecke JW.  Hypochlorous acid oxigenates the cysteine switch domain of pro-matrilysin (MM-7): A mechanism for matrix metalloproteinase activation and atherosclerotic plaque rupture by myeloperoxidase. J Biol. Chem 276:41279-41287, 2001

Fu X, Kassim SY, Parks WC, Heinecke JW.  Hypochlorous acid generated by myeloperoxidase modifies adjacent tryptophan and glycine residues in the catalytic domain of matrix metalloproteinase-7 (matrilysin): an oxidative mechanism for restraining proteolytic activity during inflammation. J Biol Chem 278:28403-28409, 2003

Fu X, Kao J, Bergt C, Kassim SY, Hug NP, d'Avignon A, Parks WC Mecham RP, Heinecke JW: Oxidative cross-linking of tryptophan to glycine restrains matrix metalloproteinase activity. Specific structural motifs control protein oxidation. J. Biol. Chem. 279:6209-6212, 2004

Wang Y, Rosen H, Madtes DK, Shao B, Martin TR, Heinecke JW, Fu X.  Myeloperoxidase inactivates TIMP-1 by oxidizing its N-terminal cysteine residue.  an oxidative mechanism for regulating proteolysis during inflammation.  J. Biol. Chem. 282(44):31826-34, 2007

Fu X, Gharib SA, Green PS, Aitken ML, Fraxer DA, Park DR, Vaisar T, Heinecke JW.  Spectral index for assessment of differential protein expression in shotgun proeomics. J. Proteome Res 7(3) 845-854, 2008.