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Richard H. Aster, MD

 
Senior Investigator
Blood Research Institute
BloodCenter of Wisconsin
 
Professor
Departments of Medicine and Pathology
Medical College of Wisconsin
 
Education and training
Postdoctoral Training
  • University of Michigan
  • Massachusetts General Hospital
  • National Institutes of Health
  • Thorndike Laboratory, Harvard Medical School
Doctoral Training
MD, University of Michigan, 1957
 
Contact information
Phone: (414) 937-6338
Fax: (414) 937-6284

Transfusion Medicine
Blood cells are targeted for destruction by antibodies in many clinically important disorders. Some of these conditions have an autoimmune etiology; others are caused by alloantibodies, isoantibodies or drug sensitivity. We are engaged in studies to improve the understanding of this family of disorders.
 
Areas of current research interest are:
  • Drug-induced immune thrombocytopenia, hemolytic anemia, and neutropenia
  • Heparin-induced thrombocytopenia and thrombosis (HIT)
  • Neonatal alloimmune thrombocytopenia (NAIT)
  • Transfusion-related acute lung injury (TRALI)

Current studies are aimed at characterizing the basis for the aberrant immune response that causes these conditions, mechanism(s) by which drugs promote binding of drug-induced antibodies to their targets and molecular characteristics of antigens recognized by pathogenic antibodies. We expect these studies will lead to improved methods to diagnose, treat and prevent hematologic diseases associated with autoimmunity, alloimmunity and drug sensitivity.

Grants

Grant: R01-HL-13629 "Hemorrhagic Diseases" - National Heart Lung and Blood Institute, (Principal Investigator) 1970-2017. 


Daniel Bougie, PhD

Research Scientist II
 
Julie Peterson, PhD

Research Scientist II
 
Anand Padmanabhan, MD, PhD

Medical Director, Assistant Investigator
 
Brian Curtis, PhD

Director, Platelet Neutrophil Immunology Lab


Andrew Lochowicz

Manager, Platelet Neutrophil Immunology Lab
 
Mark Rasmussen
Research Technologist
  
Shannon Pechauer

Research Technologist

Selected Publications
  • Bougie DW, Wilker PR, Wuitschick ED, Curtis BR, Malik M, LaVine S, Lind RN, Pereira J, Aster RH: Acute thrombocytopenia after treatment with tirofiban or eptifibatide is associated with antibodies specific for ligand-occupied GPIIb/IIIa. Blood 100: 2071-6, 2002
  • Peterson JA, Nyree CE, Newman PJ, Aster RH: A site involving the "hybrid" and PSI homology domains of GPIIIa (beta 3 integrin subunit) is a common target for antibodies associated with quinine-induced immune thrombocytopenia. Blood 101: 937-942, 2003
  • Curtis BR, Divgi A, Garritty M, Aster RH. Delayed thrombocytopenia after treatment with abciximab: A distinct clinical entity associated with the immune response to the drug. J Thromb Haemost, 2:985-992, 2004
  • Davoren A, Saving K, McFarland JG, Aster RH, Curtis BR. Neonatal neutropenia and bacterial sepsis associated with placental transfer of maternal neutrophil-specific autoantibodies. Transfusion 44:1041-46, 2004
  • Aster RH. Drug-induced immune cytopenias. Toxicology; 209: 149-153, 2005.
  • Liu CY, Battaglia M, Lee, SH, Sun QH, Aster RH, Visentin GP. Platelet factor 4 (PF4) differentially modulates CD4+CD25+ (regulatory) vs. CD4+CD25+. J immunol, 174: 2680-2686, 2005
  • Peterson JA, Balthazor SM, Curtis BR, McFarland JG, Aster RH. Maternal alloimmunization against the rare platelet-specific antigen Maxa (HPA-9b) is an important cause of neonatal alloimmune thrombocytopenia. Transfusion. 45:1487-95, 2005
  • Curtis BR, Aster RH, Cooling LL. Expression of ABH antigens on platelets. Blood 107:842-93, 2006
  • Curtis BR, Aster RH. ABH antigens on platelets. Blood 107:842-3, 2006
  • Bougie DW, Wilker P, Aster RH. Patients with quinine-induced immune thrombocytopenia have both “drug-dependent” and “drug-specific” antibodies. Blood 108:922-927, 2006
  • Von Drygalski A, Curtis BR, Bougie DW, McFarland JG, Ahl S, Limbu I, Baker KR, Aster RH. Immune thrombocytopenia in patients treated with vancomycin. New Engl J Med 356: 904-910, 2007
  • Aster RH and Bougie DW. Current Concepts: Drug-induced immune thrombocytopenia. N Engl J Med 357: 580-587, 2007
  • Bougie, DW, Benito AI, Sanchez-Albarca, LI, Torres, R, Birenbaum J, Aster RH. Immune thrombocytopenia induced by a metabolite of acetaminophen. Blood 109: 3609-3610, 2007
  • Newman PJ, Aster RH, Boylan B. Human platelets circulating in mice: applications for interrogating platelet function and survival, the efficacy of antiplatelet therapeutics, and the molecular basis of platelet immunological disorders. J Thromb Haemost. 5 (Suppl 1) 305-309, 2007
  • Curtis BR, Fick A, Lochowicz AJ, McFarland JG, Ball RH, Peterson J, Aster RH. Neonatal Alloimmune Thrombocytopenia (NAIT) Associated with Maternal-Fetal Incompatibility for Blood Group B. Transfusion, 48: 358-364, 2008
  • Peterson JA, Nelson T, Aster RH. Fine specificity of drug-dependent antibodies reactive with a restricted domain of GPIIIa. Blood, 111: 1234-1239, 2008
  • Bougie DW, Birenbaum J, Rasmussen M, Poncz M, Aster RH. Quinine-dependent, platelet-reactive monoclonals mimic antibodies found in patients with quinine-induced immune thrombocytopenia. Blood 113:1105-1111, 2009.
  • Gao C, Boylan B, Bougie D, Gill JC, Birenbaum J, Newman DK, Aster RH, Newman PJ. Eptiifbatide-induced thrombocytopenia and thrombosis in humans require FcgammaRIIa and the integrin beta3 cytoplasmic domain. J Clin Invest 119(3):504-11, 2009
  • Curtis BR, Cox NJ, Sullivan MJ, Konkashbaey A, Bowens K, Hansen K, Aster RH. The neutrophil alloantigen HN-3a (5b) is located on choline transporter-like protein 2 (CTL2) and appears to be encoded by an R>Q154 amino acid substitution. Blood 115(10):2073-6, 2010
  • Peterson JA, Gitter, ML, Kanak A, Curtis BR, McFarland JG, Bougie D, Aster, RH. New low frequency platelet glycoprotein polymorphisms associated with neonatal alloimmune thrombocytopenia. Transfusion, 50:324-333, 2010
  • Curtis BR, Sullivan MJ, Holyst MT, Szabo A, Bougie DW, Aster RH. HNA-3a-specific antibodies recognize choline transporter-like protein-2 peptides containing arginine, but not glutamine at Position 154. Transfusion 51(10):2168-74, 2011
  • Kowalska MA, Krishnaswamy S, Rauova L, Zhai L, Hayes V, Amirikian K, Esko JD, Bougie DW, Aster RH, Cines DB, Poncz M. Antibodies associated with heparin-induced thrombocytopenia (HIT) inhibit activated protein C generation: new insights into the prothrombotic nature of HIT. Blood 118(10):2882-8, 2011
  • Kanack A, Peterson JA, Sullivan MJ, Bougie DW, Curtis BR, Aster RH Full length, recombinant choline transporter-like protein 2 (CTL2) containing arginine 154 reconstitutes the epitope recognized by HNA-3a antibodies whenexpressed in HEK293 cell, Transfusion, In Press, 2012
  • Peterson JA, Pechauer S, Gitter ML, Kanack A, Curtis BR, Reese J, Kamath VM, McFarland JG, Aster RH, New platelet glycoprotein polymorphisms causing maternal immunization and neonatal alloimmune thrombocytopenia, Transfusion, In Press, 2012
  • Achterbergh A, Vermeer E, Porcelijn L, Deenik W, Daemen-Gubbels K, Bowens Aster RH, Curtis BR, Immune Thrombocytopenia Associated with Consumption of English Walnuts, Lancet, In Press, 2012
  • Bougie DW, Rasmussen M, Zhu J, Aster RH. Antibodies causing thrombocytopenia in patients treated with RGD-mimetic platelet inhibitors recognize ligand-specific conformers of αIIb3 integrin, Blood In Press 2012

Patents
  • Method of detecting heparin-induced thrombocytopenia. US Patent 5,972,718 Issued October 26, 1999
  • Method and kit for detecting heparin-induced thrombocytopenia. US Patent 5,972,717 Issued October 26, 1999
  • Nucleic acids for the detection of the Bak polymorphism in human platelet membrane glycoprotein IIb US Patent 5,652,357 Issued July 19, 1997
  • Polymorphism of human platelet membrane glycoprotein IIIa and diagnostic and therapeutic applications thereof 5,091,302 Issued February 25, 1992; US Patent 5,391,714 Patent Issued February 21, 1995; US Patent 5,670,337 Issued September 23, 1997; Japanese Patent 3,221,679 Issued August 17, 2001
  • Typing for the alloantigen HPA-3a (5b) and detection of HPA-3a-specific antibodies. Pending.

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