Research in the MACC Fund Center for Cancer and Blood Disorders at Children's Hospital of Wisconsin

Research into causes, characteristics, treatments, responses, side effects and long-term outcomes is performed every day to enhance the ongoing health and quality of life of children.

The collaboration between organizations such as Children's Research Institute, the Medical College of Wisconsin, Blood Research Institute and Midwest Athletes Against Childhood Cancer Fund ensures that the best resources come together to provide the best outcomes.

Research highlights

Researchers use new method to control bleeding in hemophilia
Results may be a small step toward a cure

Investigators at Children's Research Institute, BloodCenter of Wisconsin's Blood Research Institute and the Medical College of Wisconsin have discovered a new way to help the blood clot by having the missing clotting factor packaged in the patient's own platelets. In the October 2008 edition of Blood, investigators describe how a gene-modified bone marrow transplant can be used to initiate clotting in hemophilia. This type of approach may work in the 30 to 35 percent of hemophilia patients that have developed inhibitory antibodies against the missing clotting protein.

The bone marrow is removed from the patient and stem cells are treated with Factor VIII, a clotting factor, which is placed in the platelets. The marrow is given back to the patient, who then retains the essential clotting mechanisms to stop bleeding that otherwise would lead to complications.

For people suffering from hemophilia, this research means the potential relief of a constant, burdening disease. People who have hemophilia previously had to be treated every time they bled. Currently, they can receive treatments three times a week, but these are very costly and time consuming. The results from this study provide hope that people with hemophilia could potentially lead a disease-free life.

The scientific community once believed that hemophilia would be treated successfully by gene therapy. Research then showed that gene therapy typically resulted in the patient not retaining a substantial amount of clotting factor, which is integral in preventing serious bleeding.

This research was a collaborative effort that included investigators Qizen Shi, PhD, MD; David A. Wilcox, PhD; and Robert Montgomery, MD.

Sickle Cell Research Program

The Sickle Cell Research Program at Children's Research Institute and The Medical College of Wisconsin is one of 11 sites funded by the National Heart Lung and Blood Institute. The grant covers four sections:

  • Basic science project.
  • Patient outcomes project.
  • Sickle cell scholar.
  • Summer for sickle cell science program.

Sickle cell research programs are a collaboration of Children's Research Institute, The Medical College, BloodCenter of Wisconsin's Blood Research Institute and the MACC Fund. Research projects include:

  • Cell-free Hemoglobin, Lipid Oxidation and Nitric Oxide in Sickle Cell Disease
    • Goal: To study hemolysis-induced vascular injury in sickle cell disease.
    • Investigators: Neil Hogg, PhD; Nancy Wandersee, PhD; Cheryl Hillery, MD; J. Paul Scott, MD.

  • Mechanisms of Vascular Injury in Murine Heritable Hemolytic Anemia
    • Goal: To define the interrelationship between RBC-induced vascular injury, activation of coagulation and inflammatory pathways, and resultant tissue thrombosis and infarction.
    • Investigator: Nancy Wandersee, PhD

  • Mechanisms of Vaso-occlusion in Sickle Cell Disease: Role of Coagulation and Inflammatory Pathways
    • Goal: To examine the contribution of the coagulation pathway to the development of sickle cell-induced organ pathology using both genetic and pharmacologic approaches.
    • Investigators: Cheryl Hillery, MD; J. Paul Scott, MD

  • Red Blood Cell Adhesion in Sickle Cell Disease
    • Goal: To characterize how sickle erythrocytes stick to and injure the vascular endothelium.
    • Investigators: Cheryl Hillery, MD; J. Paul Scott, MD

  • Erythrocyte Adenine Nucleotide Metabolism
    • Goal: To characterize metabolic pools of adenine nucleotides and energy imbalance in normal and pathologic red blood cells.
    • Investigators: Cheryl Hillery, MD; Nancy Wandersee, PhD

  • High-density Lipoproteins Dysfunction and Vascular Inflammation in Sickle Cell Disease
    • Goal: To determine the mechanisms by which proinflammatory lipids and high-density lipoproteins function to impair vasodilation in sickle cell disease.
    • Investigators: Kirkwood Pritchard, PhD; Cheryl Hillery, MD

  • Asthma and Nocturnal Hypoxemia in Sickle Cell Anemia
    • Goal: Elucidate the physiologic, genetic and molecular aspects of two common co-morbid conditions, asthma and nocturnal oxygen desaturation, that increase pain in sickle cell disease.
    • Investigators: Kirkwood Pritchard, PhD; Cheryl Hillery, MD

  • Cysteinyl Leukotrienes Receptor Inhibitors: A Target For Decreasing Sickle Cell Disease-related Morbidity
    • Goal: Elucidate the role of cysteinyl leukotrienes in the pathogenesis of human and murine sickle cell disease-associated morbidity.
    • Investigators: Cheryl Hillery, MD

  • Pain in Mouse Models of Sickle Cell Disease and Hemolytic Anemia
    • Goal: Determine whether sickle cell mice have pain and whether inflammation contributes to the development of increased perception of pain in murine sickle cell disease/hemolysis.
    • Investigators: Nancy Wandersee, PhD; Cheryl Hillery, MD; Amanda M. Brandow, MD

  • Pain Outcomes in Human Sickle Cell Disease
    • Goal: Utilization and sustainable efficacy of hydroxyurea for treatment of pain in sickle cell disease. To characterize a multidisciplinary heath care model for treatment of pain in children with sickle cell disease.
    • Investigators: Amanda M. Brandow, MD; Julie A. Panepinto, MD, MSPH; J. Paul Scott, MD; Cheryl Hillery, MD

  • Quality of Life in Children With Sickle Cell Disease
    • Goals: To determine validity of PedsQL for use in children with sickle cell disease, assess well-being of parents and determine family factors that impact a child's health-related quality of life; develop a pediatric sickle cell disease specific PedsQL module.
    • Investigators: Julie A. Panepinto, MD, MSPH

  • Sickle Cell Disease/Emergency Department-related Research
    • Goals: Determine effect of Mg++ on length of stay for sickle cell disease pain; find effects of acute pain crisis on exhaled nitric oxide levels; discover relationship between CYP2D6 polymorphisms and response to pain prescriptions; identify the aspects of primary care that result in decreased nonurgent utilization of the emergency department.
    • Investigators: David Brousseau, MD, MS; Julie A. Panepinto, MD, MSPH

  • Improvement of Communication Process and Outcomes After Newborn Screening
    • Goal: Help public health to develop a mechanism for early identification and treatment of psychosocial problems that develop after newborn genetic screening using sickle trait and cystic fibrosis trait as model diseases.
    • Investigators: Julie A. Panepinto, MD, MSPH

Additional multicenter clinical/translational research projects

  • Silent Infarct Transfusion Trial.
  • Stroke with Infarct on Transfusion Changing to Hydroxyurea.
  • Arginine Supplementation in Sickle Cell Anemia.
  • Quality of Life in Children with Sickle Cell Disease and Stroke.
  • Outcome of Children Undergoing Hematopoietic Stem Cell Transplantation for Sickle Cell Disease.
  • Genetic Heterogeneity in Endothelial Gene Expression.
  • Hydroxyurea and Magnesium in Patients with Sickle Cell Disease.
  • Pharmacokinetics of Hydroxyurea in Children.
  • A Pilot Study of Hydroxyurea for the Treatment of Pulmonary Hypertension in Children and Young Adults with Sickle Cell Disease.