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Brian Curtis, PhD, D(ABMLI), MT(ASCP) SBB, Investigator

Brian R. Curtis, PhD, D(ABMLI), MT(ASCP)SBB

Sr. Director, Diagnostic Hematology

Investigator
Versiti Blood Research Institute

Director, Platelet & Neutrophil Immunology Lab
Versiti Blood Center of Wisconsin

Adjunct Faculty
Clinical and Translational Science Institute
Medical College of Wisconsin

Education and Training

Doctoral Training
University of Wisconsin-Milwaukee, PhD, 2010

B.S. Biology/Chemistry, Iowa State University, Ames, Iowa (1984)
Internship, Medical Technology Program, University of Iowa/University of Iowa Hospitals and Clinics (1985-1986)
Internship, Specialist in Blood Bank (SBB) Program, Barnes Hospital/Washington University School of Medicine (1990-1991)
Master of Science, Transfusion Medicine, Marquette University (1998)
PhD, Health Sciences (Immunology), University of Wisconsin - Milwaukee (2010)

Board Certifications

Medical Technology (MT), American Society of Clinical Pathologists (1986)
Specialist in Blood Banking (SBB) American Society of Clinical Pathologists (1991)
Diplomat, American Board of Medical Laboratory Immunology D(ABMLI) (2012)

Research and Professional Interests

Dr. Curtis has provided management and scientific direction to BloodCenter of Wisconsin’s PNIL since 1999. For over 25 years, he has been involved in research investigation and clinical laboratory testing for platelet and neutrophil antibodies and antigens. He performed research studies of erythrocyte and platelet antibodies and antigens for 4 years at Washington University Medical School in the laboratory of Dr. Hugh Chaplin Jr. Since arriving at BloodCenter of Wisconsin in 1991, he has been involved in:

  • Research
  • Assay development
  • Clinical studies of:
    - platelet and neutrophil autoimmunity
    - alloimmunity 
    - drug-dependent antibodies
    - TRALI

He serves on several national and international committees and has been an invited speaker at numerous national and international meetings. Dr. Curtis has published numerous scientific journal articles, abstracts, editorials, and text book chapters related to his work.

Contact Us

Brian R. Curtis, PhD, D(ABMLI), MT(ASCP)SBB

Sr. Director, Diagnostic Hematology
Email Phone: (414) 937-6255 Fax: (414) 937-6245

  • Research Interests

    Transfusion Medicine

    The focus of our lab’s research is on detection and characterization of platelet and neutrophil-reactive antibodies and antigens and studies of the glycoproteins that carry these antigens. The primary goal is to apply the results of this work to develop new and improved clinical tests for use by the Diagnostic Laboratories at BloodCenter of Wisconsin. 

    Drug-Dependent Platelet Antibodies

    Some people develop antibodies against their platelets, red blood cells, or white blood cells following receipt of medications. The reasons why these “drug-dependent antibodies” are produced are not completely understood. Our Platelet & Neutrophil Immunology Reference Lab currently tests for drug-dependent platelet and white blood cell antibodies, and to date, we have identified drug-dependent antibodies in patients’ blood samples for over 50 drugs, including quinine, vancomycin, sulfa-drugs, and even over-the-counter medications like ibuprofen and Tylenol (view complete list). We currently have laboratory and clinical studies in progress, together with researchers at BRI to better understand the specific epitopes on platelet proteins recognized by these antibodies and their clinical significance. 

    Studies of CD36 on Platelets

    We showed that ~3% of African-Americans lack the protein CD36/glycoprotein IV on their platelets. CD36 is a receptor for malaria-infected red blood cells, and absence of the protein from platelets and monocytes may play a role in malaria infection. Studies are ongoing to identify the rate of alloimmunization to CD36 in patients with CD36 deficiency and the role of these antibodies in immune platelet disorders. 

    Low Frequency Platelet Alloantigens

    The Platelet & Neutrophil Immunology Lab performs testing on over 400 samples each year to aid physicians in the clinical diagnosis of neonatal alloimmune thrombocytopenia (NAIT). NAIT is a disorder in pregnancy in which a mother makes antibodies against her baby’s platelets resulting in destruction of fetal and neonatal platelets leading to severe bleeding into the baby’s brain (ICH) and even death. It is thus important that laboratory testing for NAIT be thorough, including the ability to detect maternal antibodies reactive with low frequency or new platelet antigens. We are currently collaborating with Dr. Janice McFarland and researchers at BRI to develop these tools to better detect and diagnose NAIT caused by low frequency human platelet alloantigens (HPA). 

    Leukocyte Antibodies in TRALI

    Transfusion-Related Acute Lung Injury (TRALI) is a severe reaction that some patients experience following transfusion of blood or plasma. TRALI is currently the number one cause of transfusion-related death reported to the Food and Drug Administration (FDA). It is established that in a significant number of TRALI cases, the plasma from donors of the implicated blood products contains leukocyte antibodies (HLA and neutrophil) that cause activation of the patient’s neutrophils, leading to TRALI. One of the antigens targeted by such antibodies is designated human neutrophil antigen (HNA)-3a, which has been implicated in numerous severe cases of TRALI, many of them fatal. We recently identified the protein carrier (CTL2) of HNA-3a and HNA-3b, alleles of SLC44A2 and are performing biochemical and molecular research studies to determine the immunogenicity of HNA-3 antigens in the normal blood donor population. We are also investigating the use of tests that could be used to screen blood donors for antibodies against HNA-3 as a TRALI risk-reduction measure.

  • Grant Support

    Clinical and Translational Science Institute of Southeastern Wisconsin, "Development of a New Diagnostic Assay for Heparin Induced Thrombocytopenia: A Comparative Effectiveness Study,"  Role: Co-PI (2014-2015) 

  • Lab

    Allison Ujcich
    Platelet & Neutrophil Immunology Lab Supervisor 

    Mia Sullivan 
    Product Development Associate

    Krista Bowens
    Product Development Associate

  • Publications
    • Curtis BR, McFarland JG, Wu GG, Visentin GP, Aster RH. Antibodies in sulfonamide-induced immune thrombocytopenia recognize calcium-dependent epitopes on the glycoprotein IIb/IIIa complex. Blood1994;84:176-183.
    • Curtis BR, Edwards JT, Hessner MJ, Klein JP, Aster RH. Blood group A and B antigens are strongly expressed on platelets of some individuals. Blood2000;96:1574-1581.
    • Aitman TJ, Cooper LD, Norsworthy JP, Wahid FN, Gray JK, Curtis BR, McKeigue PM, Kwiatkowski D, Greenwood BM, Snow RW, Hill AV, Scott J. Malaria susceptibility and CD36 mutation. Nature 2000;405:1015-1016.
    • Curtis BR, Bussel JB, Manco-Johnson M, Aster RH, McFarland JG. Fetal and neonatal alloimmune thrombocytopenia in pregnancies involving in vitro fertilization: a report of four cases. Am J Obstet and Gynecol 2005;192:543-547.
    • Silliman CC, Curtis BR, Kopko P, Khan SY, Kelher M, Shuler R, Sannoh B, Ambruso DR. Donor antibodies to HNA-3a implicated in TRALI reactions prime neutrophils and cause PMN-mediated damage to human pulmonary microvascular endothelial cells in a two-event in vitro model. Blood 2007;109:1752-1755.
    • Von Drygalski A, Curtis BR, Bougie DW, McFarland JG, Ahl S, Limbu I, Baker KR, Aster RH. Vancomycin-induced immune thrombocytopenia. N Engl J Med 2007;356:904-910.
    • Podrez EA, Byzova TV, Febbraio M, Salomon RG, Ma Y, Valiyaveettil M, Poliakov E, Sun M, Finton PJ, Curtis BR, Chen J, Zhang R, Silverstein RL, Hazen SL. Platelet CD36 links hyperlipidemia, oxidant stress and a prothrombotic phenotype. Nature Medicine 2007;13:1086-1095.
    • Curtis BR, Fick A, Lochowicz, McFarland JG, A, Ball RH, Peterson, JA, Aster RH. Neonatal alloimmune thrombocytopenia (NATP) associated with maternal fetal incompatibility for blood group B. Transfusion 2008;48:358-364.
    • Curtis BR, Cox NJ, Sullivan MJ, Konkashbaev A, Bowens K, Hansen K, Aster RH. The neutrophil alloantigen HNA-3a (5b) is located on choline transporter- like protein 2 (CTL2) and appears to be encoded by an R>Q154 amino acid substitution. Blood 2010;115:2073-2076.
    • Reese JA, Li X, Hauben M, Aster RH, Bougie DW, Curtis BR, George JN, Vesely SK. Identifying drugs that cause acute thrombocytopenia: an analysis using 3 distinct methods. Blood 2010;116(12):2127-2133.
    • Curtis BR, Sullivan MJ, Holyst T, Szabo A, Bougie, DW, Aster RH. A 36-mer peptide from CTL2 containing arginine 154 is recognized by a subset of HNA-3a alloantibodies implicated in TRALI. Transfusion 2011; ;51:2168-2174.
    • Julie A. Peterson, Shannon M. Pechauer, Maria L. Gitter, Adam Kanack, Brian R. Curtis, Jeff Reese,Vasudeva M. Kamath, Janice G McFarland, and Richard H. Aster. New platelet glycoprotein polymorphisms causing maternal immunization and neonatal alloimmune thrombocytopenia. Transfusion2012;52(5):1117-1124.
    • Adam Kanack, Julie A Peterson, Mia Sullivan, Daniel W Bougie, Brian R Curtis, Richard H Aster. Full-length recombinant choline transporter-like protein 2 containing arginine 154 reconstitutes the epitope recognized by HNA-3a antibodies. Transfusion 2012;52(5):1112-6.
    • Roos Achterbergh, Eric Vermeer, Brian Curtis, Leendert Porcelijn, Richard H Aster, Wendy Deenik, Karin Daemen-Gubbels. Thrombocytopenia in a nutshell. Lancet 2012;379:776.
    • Brian R. Curtis. Future preventive and therapeutic targets for transfusion-related acute lung injury. Current Pharmaceutical Design 2012;18:3285-3292.
    • Krista Bowens, Mia Sullivan, Brian R. Curtis. Determination of neutrophil alloantigen HNA-3a and HNA-3b genotype frequencies in six racial groups by high-throughput 5’ exonuclease assay. Transfusion 2012 Nov; 52(11):2368-2374. 
    • GM Thomas, C Carbo, BR Curtis, K Martinod, IB Mazo, D Schatzberg, SM Cifuni, TA Fuchs, UH von Andrian, JH Hartwig, RH Aster, DD Wagner. Extracellular DNA traps are associated with pathogenesis of TRALI in humans and mice. Blood 2012; 119:6335-6343. 
    • JG McFarland, AJ Lochowicz, RH Aster, BT Chappell, BR Curtis. Improving the specificity of the PF4 ELISA in diagnosing heparin-induced thrombocytopenia. Am J Hematol 2012;87:776–781.
    • Curtis BR, McFarland JG.  Human platelet antigens - 2013.  Vox Sang 2014; 106:93-102.
    • Brian R. Curtis. Drug-induced immune thrombocytopenia: incidence, clinical features, laboratory testing, and pathogenic mechanisms. Immunohematology 2014;30(2):55-65.
    • Brian R. Curtis. Drug-induced immune neutropenia/agranulocytosis. Immunohematology 2014:30(2):95-101.
    • Anand Padmanabhan, Curtis G. Jones, Daniel W. Bougie, Brian R. Curtis, Janice G. McFarland, Demin Wang and Richard H. Aster. Heparin-independent, PF4-dependent binding of HIT antibodies to platelets: implications for HIT pathogenesis. Blood 2015;125:155-161.
    • Mia J. Sullivan, Julie Peterson, Janice G. McFarland, Daniel Bougie, Richard H. Aster, Brian R. Curtis. A new low frequency alloantigen (Khab) located on platelet glycoprotein IIIa as a cause of maternal sensitization leading to neonatal alloimmune thrombocytopenia. Transfusion 2015;55:1584-1585.
    • DM Arnold, BR Curtis, T Bakchoul. Recommendations for standardization of laboratory testing for drug-induced thrombocytopenia. J Thromb Haemost 2015; Apr;13(4):676-678.
    • Jessica A. Reese, Daniel W. Bougie, Brian R. Curtis, Deirdra R.Terrell, Sara K. Vesely, Richard H. Aster, James N. George. Drug-induced thrombotic microangiopathy: Experience of the Oklahoma registry and the BloodCenter of Wisconsin. Am J Hematol 2015; 90(5):406-410.
    • Brian R Curtis, Ashley Roman, Mia Sullivan, Cindy Raven, Judy Larison, LeeAnn Weitekamp. Two Cases of Maternal Alloimmunization Against Human Neutrophil Alloantigen-4b, One Causing Severe Alloimmune Neonatal Neutropenia. Transfusion 2015;Sep 1. doi: 10.1111/trf.13287. [Epub ahead of print].
    • Anand Padmanabhan, Curtis G. Jones, Daniel W. Bougie, Brian R. Curtis, Janice G. McFarland, Demin Wang, and Richard H. Aster. A PF4-dependent CD62p expression assay selectively detects serotonin releasing antibodies in patients suspected of HIT. J Thromb Haemost 2015; Jul 16;114(5). [Epub ahead of print].
    • Brian R. Curtis. Recent progress in understanding the pathogenesis of fetal and neonatal alloimmune thrombocytopenia. Br J Haematol 2015;Sep 7. doi: 10.1111/bjh.13639. [Epub ahead of print].
  • Other
    • 1996 - U.S. Serial No. 5,585,243.  Inventors - RH Aster and BR Curtis.  METHOD OF DETECTING CYTOPENIA THAT IS MEDIATED DRUG-DEPENDENT ANTIBODY BONDING TO BLOOD CELLS
    • 2013 - Patent Pending.  Inventor - BR Curtis.  METHOD OF SIMULTANEOUS DETECTION OF HEPARIN-DEPENDENT IMMUNOGLOBULINS TYPES G,A, AND M.
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