Fu Laboratory

Yi Wang, Ph.D.

A disintegrin and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) is a plasma metalloproteinase that specifically cleaves large multimeric forms of von Willebrand factor (VWF) to smaller forms. Deficiency of this enzyme has been associated with thrombotic thrombocytopenic purpura, as well as diseases involving systemic inflammation. My current research focuses on the regulation of ADAMTS13 by reactive oxygen species produced by inflammatory cells. Using mass spectrometry and biochemistry approaches, we demonstrated that oxidants derived from phagocytes inactivate ADAMTS13 and loss of the enzyme activity correlates with oxidation of specific amino residues of ADAMTS13. We are now evaluating the extent of ADAMTS13 oxidation in plasma from patients with inflammatory diseases, providing the evidence of an oxidative mechanism for inactivating ADAMTS13 in vivo.

In addition, I am currently the operations manager of the Mass Spectrometry Laboratory and have a great interest in pursuing various collaborations with researchers who wish to use mass spectrometry and proteomics techniques to identify proteins and peptides. My long term goal is to provide mass spectrometry capabilities and proteomics tools to the Bloodworks Northwest’s research community.

Yi Wang, Ph.D. Publications

1. Wang Y, Chen J, Ling M, López JA, Chung D, Fu X. Oxidation of key methionine residues in the N-terminal domains of ADAMTS13 correlates with loss of its proteolytic activity. Blood (ASH Annual Meeting Abstracts), 2011, 118: 3276.
2. Herrero R, Kajikawa O, Matute-Bello G, Wang Y, Hagimoto N, Mongovin S, Wong V, Park D, Brot N, Heinecke JW, Rosen H, Goodman RB, Fu X, Martin TR. The biological Activity of FasL in humans and mice is determined by the structure of its stalk region. J Clin. Invest. 2011, 121(3): 1174-1190
3. Wang Y, Cao J, Wang X, Zeng S. Stereoselective transport and uptake of propranolol across human intestinal Caco-2 cell monolayers. Chirality, 2010, 22(3): 361-368.
4. 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, 2010, 115(3): 706-712.
5. Rosen H, Klebanoff SJ, Wang Y, Brot N, Heinecke JW, Fu X. Methionine oxidation contributes to bacterial killing by the myeloperoxidase system of neutrophils. Proc Natl Acad Sci USA, 2009, 106(44): 18686-18691.
6. Zhu F*, Wang Y*, Zeng S, Fu X, Wang L, Cao J. Involvement of annexin A1 in multidrug resistance of K562/ADR cells identified by the proteomic study. OMICS, 2009, 13(6): 467-476 (Zhu F and Wang Y contributed equally to this work).
7. Yuan W, Wang Y, Heinecke JW, Fu X. Hypochlorous acid converts the gamma-glutamyl group of glutathione disulfide to 5-hydroxybutyrolactam, a potential marker for neutrophil activation. J Biol Chem, 2009, 284(39): 26908-26917
8. 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, 2007, 282(44): 31826-31834.
9. Fu X, Wang Y, Kao J, Irwin A, d’Avignon A, Mecham RP, Parks WC, Heinecke JW. Specific sequence motifs direct the oxygenation and chlorination of tryptophan by myeloperoxidase, Biochemistry, 2006, 45(12): 3961-3971.
10. Wang Y, Cao J, Zeng S. Involvement of P-glycoprotein in regulating cellular levels of Ginkgo flavonols: quercetin, kaempferol, and isorhamnetin. J Pharm Pharmacol, 2005, 57(6): 751-758.