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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 (1998)

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

Xiaoyun Fu, Ph.D.
Research Associate Professor of Medicine
Division of Hematology
University of Washington School of Medicine

Associate Member
Director of Mass Spectrometry Laboratory
Puget Sound Blood Center

Office Address:
Puget Sound Blood Center
Box 359190
BRI Room 3011
1551 Eastlake Avenue E, Suite 100
Seattle, WA 98102

Phone:   (206) 568-2250
Fax:       (206) 587-6056
E-mail:   xyfu@u.washington.edu

 

CURRENT RESEARCH INTERESTS

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


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 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 oxidative regulation of blood coagulation proteins. We are currently attempting to understand the molecular mechanisms through which neutrophil-derived oxidants regulate von Willebrand factor (vWF) and its cleavage enzyme, ADAMTS13 function. These studies are in collaboration with Dr. José López' research group. The long-term goal 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 use 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.

Gharib SA, Green PS, Aitken ML, Frazer DA, Park DR, Vaisar T, Heinecke JW, Fu X.  Mapping the lung proteome in cystic fibrosis. J. Proteome Res.  8(6):3020-8, 2009

Yuan W, Wang Y, Heinecke JW, Fu X.  Hypochlorous acid converts the g-glutamyl group of glutathione disulfide to 5-hydroxy-butyrolactam: a potential marker for neutrophil activation. J. Biol. Chem. 284(39):26908-17, 2009

Rosen H, Klebanoff SJ, Wang Y, Brot N, Heinecke JW,  Fu X.  Methionine oxidation contributes to bacterial killing by the myeloperoxidase system of neutrophilsPNAS, 106(44):18686-91, 2009.

Chen J, Fu X*, Wang Y,  Ling M, McMullen B, Kulman J, Chung D, López JA.  Oxidative modification of von Willebrand factor by neutrophil oxidants inhibits its cleavage by ADAMTS13. Blood, 115(3) 706-12, 2010. (Chen J and Fu X contributed equally to this work)