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CURRENT RESEARCH INTERESTS
Thrombotic
thrombocytopenic pupura, ADAMTS-13 biology, and platelet functions
under fluid shear stress
RESEARCH
DESCRIPTION
Research in our group has been concentrated on platelet functions under
high fluid shear stress. Our aim is to understand how platelets
interact with subendothelium, with each other, and with other blood
cells under flow condition. We are particularly interested in
dissecting signal pathways that are initiated by the interaction of
platelet glycoprotein Ib-IX-V complex and von Willebrand factor.
Our
research also focuses on defining mechanisms through which the
endothelium-derived ultra-large von Willebrand factor multimers are
cleaved by the ADAMTS-13 metalloprotease in vivo and what roles of
this proteolysis process may play in the development of thrombosis.
Such efforts will
allow us to identify agents that selectively block pathophysiological
thrombosis without affecting physioligcal hemostatic function of
platelets.
SELECTED PUBLICATIONS
Dong J.F.,
Moake J.L., Nolasco L., Bernardo A., Arceneaux W., Shrimpton C.N.,
Schade A.J., McIntire L.V., Fujikawa K., López J.A.
(2002) ADAMTS-13 rapidly cleaves newly secreted ultra-large von
Willebrand factor multimers on the endothelial surface under flowing
conditions. Blood 100(12):4033-4039.
Dong
J.F., Moake J.L.,
Bernardo A.,
Fujikawa K.,
Ball C.,
Nolasco L.,
López J.A.., Cruz M.A.
(2003) ADAMTS-13
metalloprotease interacts with the endothelial cell-derived
ultra-large von Willebrand factor.
J Biol. Chem.
278(32):29633-29639.
Padilla A.,
Moake J.L.,
Bernardo A.,
Ball C.,
Wang Y.,
Arya M.,
Nolasco L.,
Turner N.,
Berndt M.C.,
Anvari B.,
López J.A.., Dong
J.F. (2004) P-selectin anchors newly released ultra-large von Willebrand factor
multimers to the endothelial cell surface. Blood 103(6):2150-2156.
Bernardo A.,
Ball C.,
Nolasco L.,
Moake J.F.,
Dong
J.F.
(2004) Effects of
inflammatory cytokines on the release and cleavage of the endothelial
cell-derived ultra-large von Willebrand factor multimers under flow. Blood
104(1):100-106.
Bernardo A.,
Ball C.,
Nolasco L.,
Choi H.,
Moake J.L.,
Dong
J.F. (2005) Platelets
adhered to endothelial cell-bound ultra-large von Willebrand factor
strings support leukocyte tethering and rolling under high shear
stress. J
Thromb Haemost 3(3):562-570.
Tao Z.,
Wang Y.,
Choi H.,
Bernardo A.,
Nishio K.,
Sadler J.E.,
López J.A., Dong
J.F. (2005) Cleavage
of ultra-large multimers of von Willebrand factor by
C-terminal-truncated mutants of ADAMTS-13 under flow. Blood
106(1):141-143.
Li
Liu, Tao Z, Ruan, Moake J, Dong
J.F. (2005) Platelet-derived ADAMTS-13.
J Thromb. Haemost. 3(11):2536-2544
Tao
Z, Peng Y Cal S, Moake J, Lopez JA, Dong
J.F (2005) CUB domain anchors ADAMTS-13 to ULVWF strings under
flow conditions. Blood
106(13):4139-4145
Tao
Z, Anthony K, Peng Y, Choi H, Nolasco L, Rice L, Moake JL, Dong JF.
(2006) Novel ADAMTS-13
mutations in an adult with delayed onset thrombotic thrombocytopenic
purpura. J Thromb Hemost. 4:1931-1935
Choi
H, Aboulfatova K, Pownall HJ, Cook R, Dong
JF. (2008) shear-induced disulfide bond formation regulates
adhesion activity of von Willebrand factor. J
Biol. Chem. 282:35604-35611
Li
Y, Choi H, Zhou Z, Nolasco
L, Pownall HJ,
Voorberg J, Moake
JL, Dong J.F. (2008)
Covalent regulation of ULVWF string formation and elongation on
endothelial cells under flow conditions. J
Thromb. Hemost 6(7):1135-1143
Wu
T, Lin J, Cruz MA, Dong J.F.
and Zhu C. (2009) Force-induced Cleavage of Single VWF
A1A2A3-tridomains by ADAMTS-13. Blood
( co-corresponding author) 115:370-378
Saunders
J, Nambi V, Kimball KT, Virani S, Yang E, Bergeron A, Athamneh H,
Kumar A, Morrisett JD,
Lumsden A, Chen J, Lin P,
Bechara C, Ballantyne CM, Dong
J.F. (2010) Variability
and Persistence of Aspirin Response to lower extremity peripheral
artery disease patients. J. Vasc.
Surg. 53(3);668-675
Yeh
HC, Zhou X, Choi H, Tekeoglu S, May W, Turner N, Scheiflinger F, Moake
JL, Dong JF.
(2010) Disulfide bond
reduction of von Willebrand factor by ADAMTS-13. J Thromb. Hemost. 8:2278-2288
Campos
M, Sun W, Yu F, Barbalic M, Tang T, Chambless LE, Ballantyne CM,
Folsom AR, Boerwinkle E, Dong
J.F.
(2011)
Genetic Determinants of Plasma von Willebrand Factor Antigen Levels: A
Target Gene SNP and Haplotype Analysis of ARIC Cohort. Blood
(Epub ahead of print)
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