CURRENT RESEARCH INTERESTS
Platelets and coagulation abnormalities associated with non-hematologic diseases, von Willebrand factor and ADAMTS-13 biology in thrombotic microangiopathy, and platelet functions under fluid shear stress
Research conducted in our laboratory focuses on three main areas.
First, we conduct research to understand mechanisms through which platelet and coagulation become defective in non-hematologic diseases such as traumatic brain injury, severe infections and cancer. We also work to develop early markers for the diagnosis of these defects and to identify targeted therapeutics.
Second, we study structure and function correlations of the adhesion ligand von Willebrand factor and its cleaving metalloprotease ADAMTS-13. We also investigate how changes in these correlations result in thrombotic conditions called thrombotic and thrombocytopenic purpura (TTP) and transplant-associated microangiopathy.
Third, we are interested in dissecting signal pathways in platelets that are initiated and propagated by the interaction of platelet glycoprotein Ib-IX-V complex and von Willebrand factor under hydrodynamic conditions such as blood flow. We specifically focus on how changes in fluid hydrodynamics induced by arterial stenosis and left ventricular assist devices affect the GP Ib-von Willebrand factor interaction, leading to thrombotic and bleeding complications.
Campos, M., Sun, W., Yu, F., Barbalic, M., Tang, T., Chambless, L.E., Ballantyne, C.M., Folsom, A.R., 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. 117(19):5224-30.
Campos M, Buchanan A, Yu F, Barbalic M, Xiao Y, Chambless LE, Wu KK, Folsom AR, Boerwinkle E, Dong J.F. (2012) Influence of single nucleotide polymorphisms in factor VIII and von Willebrand factor genes on plasma factor VIII activity: the ARIC study. Blood. 119(80):1929-34
Zhou Z, Gushiken F.C., Bolgiano D, Salsbery B.J., Aghakasiri N., Jing N., Wu X., Vijayan V., Rumbault R.E., Adachi R., Lopez J.A., Dong J.F., (2013) STAT3 Regulates Collagen-Induced Platelet Aggregation Independent of its Transcription Factor Activity. Circulation. 127(4):476-85
Edelstein, L.C., Simon, L.M., Montoya, R.T., Holinstat, M., Chen, E.S., Bergeron, A., Kong, X., Nagalla, S., Mohandas, N., Cohen, D.E., Dong, J.F.; Shaw, C.; Bray, P.F. 2013. Racial differences in human platelet PAR4 reactivity reflect expression of PCTP and miR-376c. Nat. Med. 19:1609-1616.
Nascimbene, A., Hernandez, R., George, J.K., Parker, A., Bergeron, A.L., Pradhan, S., Vijayan, K.V., Civitello, A., Simpson, L., Nawrot, M. Lee V, Mallidi HR, Delgado RM., Dong J.F., O.H.Frazier. (2014). Association between cell-derived microparticles and adverse events in patients with nonpulsatile left ventricular assist devices. J. Heart Lung Transplant. J Heart Lung Transplant. 33(5):470-477
Tian Y, Salsbery B, Wang M, Yuan H, Yang J, Zhao Z, Wu X, Zhang Y, Konkle BA, Thiagarajan P, Li M, Zhang J, Dong JF. (2015) Brain-derived microparticles induce systemic coagulation in a murine model of traumatic brain injury. Blood 125:2151-2159
Song J, Chen F, Campos M, Bolgiano D, Houck K, Chambless LE, Wu KK, Folsom AR, Couper D, Boerwinkle E, Dong JF. (2015) Quantitative Influence of ABO Blood Groups on Factor VIII and Its Ratio to von Willebrand Factor, Novel Observations from an ARIC Study of 11,673 Subjects. PLoS One. 10(8):e0132626
Yuan H, Houck K, Tian Y, Bharadwaj U, Hull K, Wu XP, Tweardy DJ, Romo D, Fu XY, Zhang Y, Zhang JN, Dong JF. (2015) Piperlongumine Blocks JAK2-STAT3 to Inhibit Collagen-induced Platelet Reactivity Independent of Reactive Oxygen Species. PLos One 10(12):e0143964
Wang R, Stone RL, Kaelber JT, Rochat RH, Nick AM, Vijayan KV, Afshar-Kharghan V, Schmid MF, Dong JF, Sood AK, Chiu W. (2015) Electron cryotomography reveals ultrastructure alterations in platelets from patients with ovarian cancer. Proc Natl Acad Sci USA. 17;112:14266-14271. PMID: 26578771
Zhao Z, Wang M, Tian Y, Hilton T, Salsbery B, Zhou EZ, Wu XP, Thiagarajan P, Boilard E, Li M, Zhang JN, Dong JF (2016) Cardiolipin-mediated procoagulant activity of mitochondria induces traumatic brain injury-associated coagulopathy in mice. Blood 127:2763-2772