Our laboratory is interested in genetic disorders of bleeding and thrombosis, focusing on blood platelets as the tools to understand the molecular basis of these disorders in humans. Blood platelets are generated from bone marrow stem cells, serving not only to control normal bleeding, but involved also in excessive clotting that may predispose to pathological disorders such as heart attacks and stroke. We have developed a unique infrastructure for studying the genetics of platelet diseases using RNA profiling techniques. In parallel, we have developed means for changing gene expression as a means of potentially treating bleeding disorders such as hemophilia. For our NYSTEM proposal, we have developed novel means of infecting bone marrow stem cells to specifically target the deficient protein (factor VIII) in bone marrow stem cells that are the precursors for circulating blood platelets. If successful, this would provide a means of performing autologous bone marrow transplantation to correct the bleeding in hemophiliacs.
Gnatenko DV, Dunn JJ, Schwedes J, Bahou WF. Transcript profiling of human platelets using microarray and serial analysis of gene expression (SAGE). Methods Mol Biol. 2009;496:245-72. Review.
Damon AL, Scudder LE, Gnatenko DV, Sitaraman V, Hearing P, Jesty J, Bahou WF. Altered bioavailability of platelet-derived factor VIII during thrombocytosis reverses phenotypic efficacy in haemophilic mice. Thromb Haemost. 2008 Dec;100(6):1111-22.
Gnatenko DV, Zhu W, Bahou WF. Multiplexed genetic profiling of human blood platelets using fluorescent microspheres. Thromb Haemost. 2008 Nov;100(5):929-36.
Senzel L, Gnatenko DV, Bahou WF. Genomic and proteomic applications in diagnosis of platelet disorders and classification. Semin Thromb Hemost. 2008 Sep;34(6):532-8.
Gnatenko DV, Perrotta PL, Bahou WF. Proteomic approaches to dissect platelet function: Half the story. Blood. 2006 Dec 15;108(13):3983-91.
Watson SP, Bahou WF, Fitzgerald D, Ouwehand W, Rao AK, Leavitt AD; ISTH Platelet Physiology Subcommittee. Mapping the platelet proteome: a report of the ISTH Platelet Physiology Subcommittee. J Thromb Haemost. 2005 Sep;3(9):2098-101.
Gnatenko DV, Cupit LD, Huang EC, Dhundale A, Perrotta PL, Bahou WF. Platelets express steroidogenic 17beta-hydroxysteroid dehydrogenases. Distinct profiles predict the essential thrombocythemic phenotype. Thromb Haemost. 2005 Aug;94(2):412-21.
Cupit LD, Schmidt VA, Gnatenko DV, Bahou WF. Expression of protease activated receptor 3 (PAR3) is upregulated by induction of megakaryocyte phenotype in human erythroleukemia (HEL) cells. Exp Hematol. 2004 Oct;32(10):991-9.
Gnatenko DV, Wu Y, Jesty J, Damon AL, Hearing P, Bahou WF. Expression of therapeutic levels of factor VIII in hemophilia A mice using a novel adeno/adeno-associated hybrid virus. Thromb Haemost. 2004 Aug;92(2):317-27.