Lotte van Hessem
Beth Israel Deaconess Medical Center
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Publication
Featured researches published by Lotte van Hessem.
Journal of Clinical Investigation | 2012
Reema Jasuja; Freda Passam; Daniel R. Kennedy; Sarah H. Kim; Lotte van Hessem; Lin Lin; Sheryl R. Bowley; Sucharit S. Joshi; James Dilks; Bruce Furie; Barbara C. Furie; Robert Flaumenhaft
Thrombosis, or blood clot formation, and its sequelae remain a leading cause of morbidity and mortality, and recurrent thrombosis is common despite current optimal therapy. Protein disulfide isomerase (PDI) is an oxidoreductase that has recently been shown to participate in thrombus formation. While currently available antithrombotic agents inhibit either platelet aggregation or fibrin generation, inhibition of secreted PDI blocks the earliest stages of thrombus formation, suppressing both pathways. Here, we explored extracellular PDI as an alternative target of antithrombotic therapy. A high-throughput screen identified quercetin-3-rutinoside as an inhibitor of PDI reductase activity in vitro. Inhibition of PDI was selective, as quercetin-3-rutinoside failed to inhibit the reductase activity of several other thiol isomerases found in the vasculature. Cellular assays showed that quercetin-3-rutinoside inhibited aggregation of human and mouse platelets and endothelial cell-mediated fibrin generation in human endothelial cells. Using intravital microscopy in mice, we demonstrated that quercetin-3-rutinoside blocks thrombus formation in vivo by inhibiting PDI. Infusion of recombinant PDI reversed the antithrombotic effect of quercetin-3-rutinoside. Thus, PDI is a viable target for small molecule inhibition of thrombus formation, and its inhibition may prove to be a useful adjunct in refractory thrombotic diseases that are not controlled with conventional antithrombotic agents.
Archive | 2014
Carol Khodier; Lynn VerPlank; Partha Nag; Jun Pu; Jacqueline Wurst; Tatiana Pilyugina; Chris Dockendorff; Christine N. Galinski; Alissa A. Scalise; Freda Passam; Lotte van Hessem; James Dilks; Daniel R. Kennedy; Robert Flaumenhaft; Michelle Palmer; Sivaraman Dandapani; Benito Munoz; Stuart L. Schrieber
Blood | 2013
Partha Nag; Christine N. Galinski; Sheryl R. Bowley; Roelof H. Bekendam; James Dilks; Alissa A. Scalise; Lotte van Hessem; Jun Pu; Tatiana Pilyugina; Sivaraman Dandapani; Benito Munoz; Robert Flaumenhaft
Archive | 2014
Carol Khodier; Lynn VerPlank; Partha Nag; Jun Pu; Jacqueline Wurst; Tatiana Pilyugina; Chris Dockendorff; Christine N. Galinski; Alissa A. Scalise; Freda Passam; Lotte van Hessem; James Dilks; Daniel R. Kennedy; Robert Flaumenhaft; Michelle Palmer; Sivaraman Dandapani; Benito Munoz; Stuart L. Schrieber
Archive | 2014
Carol Khodier; Lynn VerPlank; Partha Nag; Jun Pu; Jacqueline Wurst; Tatiana Pilyugina; Chris Dockendorff; Christine N. Galinski; Alissa A. Scalise; Freda Passam; Lotte van Hessem; James Dilks; Daniel R. Kennedy; Robert Flaumenhaft; Michelle Palmer; Sivaraman Dandapani; Benito Munoz; Stuart L. Schrieber
Archive | 2014
Carol Khodier; Lynn VerPlank; Partha Nag; Jun Pu; Jacqueline Wurst; Tatiana Pilyugina; Chris Dockendorff; Christine N. Galinski; Alissa A. Scalise; Freda Passam; Lotte van Hessem; James Dilks; Daniel R. Kennedy; Robert Flaumenhaft; Michelle Palmer; Sivaraman Dandapani; Benito Munoz; Stuart L. Schrieber
Archive | 2014
Carol Khodier; Lynn VerPlank; Partha Nag; Jun Pu; Jacqueline Wurst; Tatiana Pilyugina; Chris Dockendorff; Christine N. Galinski; Alissa A. Scalise; Freda Passam; Lotte van Hessem; James Dilks; Daniel R. Kennedy; Robert Flaumenhaft; Michelle Palmer; Sivaraman Dandapani; Benito Munoz; Stuart L. Schrieber
Archive | 2014
Carol Khodier; Lynn VerPlank; Partha Nag; Jun Pu; Jacqueline Wurst; Tatiana Pilyugina; Chris Dockendorff; Christine N. Galinski; Alissa A. Scalise; Freda Passam; Lotte van Hessem; James Dilks; Daniel R. Kennedy; Robert Flaumenhaft; Michelle Palmer; Sivaraman Dandapani; Benito Munoz; Stuart L. Schrieber
Archive | 2014
Carol Khodier; Lynn VerPlank; Partha Nag; Jun Pu; Jacqueline Wurst; Tatiana Pilyugina; Chris Dockendorff; Christine N. Galinski; Alissa A. Scalise; Freda Passam; Lotte van Hessem; James Dilks; Daniel R. Kennedy; Robert Flaumenhaft; Michelle Palmer; Sivaraman Dandapani; Benito Munoz; Stuart L. Schrieber
Archive | 2014
Carol Khodier; Lynn VerPlank; Partha Nag; Jun Pu; Jacqueline Wurst; Tatiana Pilyugina; Chris Dockendorff; Christine N. Galinski; Alissa A. Scalise; Freda Passam; Lotte van Hessem; James Dilks; Daniel R. Kennedy; Robert Flaumenhaft; Michelle Palmer; Sivaraman Dandapani; Benito Munoz; Stuart L. Schrieber