This proposal describes a five year research program investigating pathophysiology of the human thrombotic disease thrombotic thrombocytopenic purpura (TTP). The PI and co-PI are both relatively new Assistant Professors in Hematology/Oncology at the University of Iowa. Other personnel will include research assistants, post-doctoral associates, and graduate students. The experiments proposed focus on understanding the pathophysiology of TTP, an uncommon but serious human thrombotic disease that still carries and ~20% mortality rate. The PI has already developed an animal model of TTP, which will be used to examine in detail, the role of the blood clotting protein, von Willebrand Factor, in this disease. These studies have the potential to further our understanding of TTP, a complex and important disease in humans. This research will build upon the applicant's prior research experience in this field, and it is anticipated that it will contribute greatly to his beginning career as an independent investigator. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page

Public Health Relevance

We are investigating the human blood clotting disease TTP. This is a rare, but serious disease (1 case per 250,000 people per year). Unfortunately TTP strikes usually without preceding symptoms, usually in people less than 50 years of age. Mortality for this disease is still ~ 20% and treatment also carries significant risks.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Study Section
Hemostasis and Thrombosis Study Section (HT)
Program Officer
Kindzelski, Andrei L
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University of Iowa
Internal Medicine/Medicine
Schools of Medicine
Iowa City
United States
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Ng, Christopher; Motto, David G; Di Paola, Jorge (2015) Diagnostic approach to von Willebrand disease. Blood 125:2029-37
Tati, Ramesh; Kristoffersson, Ann-Charlotte; Ståhl, Anne-Lie et al. (2013) Complement activation associated with ADAMTS13 deficiency in human and murine thrombotic microangiopathy. J Immunol 191:2184-93
Dayal, Sanjana; Wilson, Katina M; Motto, David G et al. (2013) Hydrogen peroxide promotes aging-related platelet hyperactivation and thrombosis. Circulation 127:1308-16
Case, Adam J; Madsen, Joshua M; Motto, David G et al. (2013) Manganese superoxide dismutase depletion in murine hematopoietic stem cells perturbs iron homeostasis, globin switching, and epigenetic control in erythrocyte precursor cells. Free Radic Biol Med 56:17-27
Barr, Justin D; Chauhan, Anil K; Schaeffer, Gilbert V et al. (2013) Red blood cells mediate the onset of thrombosis in the ferric chloride murine model. Blood 121:3733-41
Gandhi, Chintan; Motto, David G; Jensen, Melissa et al. (2012) ADAMTS13 deficiency exacerbates VWF-dependent acute myocardial ischemia/reperfusion injury in mice. Blood 120:5224-30
Motto, David (2012) Endothelial cells and thrombotic microangiopathy. Semin Nephrol 32:208-14
Khan, M M; Motto, D G; Lentz, S R et al. (2012) ADAMTS13 reduces VWF-mediated acute inflammation following focal cerebral ischemia in mice. J Thromb Haemost 10:1665-71