NATIONAL BLOOD FOUNDATION AWARDS $250,000 IN GRANTS

Funding to Support Innovative Research Development in Scientific Aspects of
Cellular Therapies, Transfusion Medicine and Tissue Transplantation

BETHESDA, MD – The National Blood Foundation (NBF) Board of Trustees is pleased to announce the recipients of the 2004 NBF Scientific Research Grants. Each grant recipient receives $50,000 to pursue a one or two-year research project in the fields of blood banking and transfusion medicine. The recipients this year are Ognjen Gajic, MD; Andres Hidalgo, PhD; Qizhen Shi, MD, PhD; X. Long Zheng, MD, PhD; and James C. Zimring, MD, PhD.

“The 2004 NBF grant recipients represent an exceptional group of emerging researchers with diverse backgrounds, all of whom have made significant contributions to the fields of blood banking and transfusion medicine,” said John D. Roback, MD, PhD, chair of NBF’s Grants Review Committee (GRC). “Since the grants program began in1985, NBF has continued to encourage original scientific research by awarding $3.3 million to more than 119 scientific researchers.”

The NBF Scientific Research Grant applications are evaluated on the basis of their scientific merit, relevance to and impact on transfusion medicine and science, focus and appropriateness to the scope of funding, and likelihood of yielding meaningful data.

Ognjen Gajic, MD
Transfusion-Related Acute Lung Injury in the Medical Intensive Care Unit

Gajic, the principal investigator for this study, is the Ralph and Marian C. Falk Pulmonary Research Fellow and an instructor of medicine at the Mayo Clinic College of Medicine in Rochester, Minn. Gajic’s team for this one-year study includes: Rolf D. Hubmayr, MD; Breanndan S. Moore, MD; Rimki Rana, MD; Otis B. Rickman, DO; Jose L. Mendez, MD; Steven R. Holets, RRT; Laura K. Evanson, RN; and Darrel C. Schroeder, MS. The group will investigate the development of Transfusion Related Acute Lung Injury (TRALI) in critically ill patients who require mechanical ventilation. The team found that transfusion of blood products, especially fresh frozen plasma, and ventilator settings posed major risk factors for the development of acute lung injury. Gajic’s hypothesis is that patients who receive blood products containing anti-leukocyte antibodies and/or inflammatory cytokines are more likely than patients who do not receive such products to subsequently develop acute lung injury. The study will focus on medical critically ill patients requiring mechanical ventilation.

Gajic earned his medical degree from the University of Sarajevo in Sarajevo, Bosnia and Herzegovina in 1987, and is currently in the Master’s Program in Clinical Research at the Mayo Clinic College of Medicine in Rochester, Minn. He also is director of the Critical Care Web site for the American Thoracic Society. From 1998 until 1999, Gajic was chief resident at New York Methodist Hospital at Cornell University Medical College in Brooklyn, NY. After his term as chief resident, he was a Critical Care and Pulmonary Fellow at the Mayo Clinic College of Medicine in Rochester, Minn., until 2003. Gajic was honored with Mayo Clinic’s Academic Clinician Award in 2001, and the Society of Critical Care Medicine in Training Award in 2004.

Andres Hidalgo, PhD
Optimizing Cord Blood Transplantation by Upregulation of Selectin Ligands

Hidalgo is currently a postdoctoral fellow studying how blood stem cells travel between blood and bone marrow, in the Department of Medicine at Mount Sinai School of Medicine in New York. His grant will fund a one-year study focusing on how stem cells obtained from cord blood go to the bone marrow during transplantation. Hidalgo and his colleague, Paul S. Frenette, MD, propose to investigate whether enhancing the function of certain receptors on stem cells from cord blood can increase the number of stem cells that migrate to the bone marrow. The results of this study may enhance the engraftment in transplanted patients and benefit gene therapy by allowing for improved migration to the bone marrow.

Hidalgo studied at the Universidad Autonoma de Madrid in Madrid, Spain, earning a bachelor’s degree in science in 1993, and a doctorate in molecular biology and immunology in 1999. In 1997, and again in 1998, he worked on molecular target validation, chemokines and signal transduction both in vivo and in vitro at Millennium Pharmaceuticals Inc., in Cambridge, Mass. Hidalgo received a fellowship from Cooleys Anemia Foundation in 2002.

Qizhen Shi, MD, PhD
Targeting Human Platelet Glycoprotein Ibα Gene Expression to the Platelets of Bernard-Soulier Syndrome Mice

Shi, a senior postdoctoral fellow in both the Department of Pediatrics at the Medical College of Wisconsin and the Blood Research Institute of The Blood Center of Southeastern Wisconsin in Milwaukee, Wis., has been studying the platelet defect in patients with Bernard-Soulier Syndrome (BSS), a severe congenital platelet disorder resulting from a deficiency of platelet surface protein. Platelet transfusions typically are needed for the treatment of hemorrhage, however this solution is only temporarily effective. Gene therapy may be an alternative approach that offers a more long-term solution. Shi will use this one-year grant to express the normal gene in platelets of mice that lack that gene (a model for BSS) in an attempt to correct the associated bleeding disorder. Shi will evaluate the feasibility of future gene therapy as an alternative for treatment of the bleeding disorder in BSS.

Shi attended Fujian Medical University in Fujian, China, earning a medical degree in 1990, a master’s of science degree in hematology in 1993, and a doctorate in molecular biology in 1998. Shi was an attending physician in hematology at the Fujian Institute of Hematology in Fujian, China, from 1995 until 2000, before becoming a postdoctoral fellow at the Medical College of Wisconsin, Department of Pediatrics-MFRC, Hematology/Oncology. In 2003, Shi won first place at the Childrens Hospital of Wisconsin Resident and Fellow Research Days for work performed on GPIbα, Tissue-specific expression of GPIbα in human megakarayocytes.

X. Long Zheng, MD, PhD
Characterization of Autoantibodies Directed Against ADAMTS13 Metalloprotease Underlying Thrombotic Thrombocytopenic Purpura

Zheng is a tenure-track assistant professor and medical director of the Coagulation Laboratory in the Department of Pathology and Laboratory Medicine at the Children’s Hospital of Philadelphia and the University of Pennsylvania School of Medicine in Philadelphia, Pa. Zheng and his team, including Julie Ai, MD, PhD, and Ning Li, BS, will use this one-year grant to examine the immunologic basis for Thrombotic Thrombocytopenic Purpura (TTP) in patients who have low ADAMTS13 levels, but who do not have an obvious inhibitor. Zheng’s hypothesis is that such patients develop non-inhibitory antibodies against ADAMTS13 that cause disease by enhancing clearance of ADAMTS13, rather than inhibition of ADAMTS13 enzymatic function per se. He has developed a panel of epitope-tagged C-terminal deletion mutants of the ADAMTS13 protein, as well as a novel ELISA assay with which to detect anti-ADAMTS13 antibodies. The study will determine the prevalence of both inhibitory and non-inhibitory antibodies in TTP patients; the relevant ADAMTS13 target domains for said antibodies; and compare the clinical course of patients with inhibitory and non-inhibitory antibodies.

Zheng earned his medical degree from the Jiangxi Medical College in China and his doctorate in molecular and cellular biology from the University of Vienna in Vienna, Austria. In 1999, Zheng went to the Washington University School of Medicine in St. Louis, Mo., to complete a residency in clinical pathology and then a fellowship in blood banking/transfusion medicine. Zheng also was awarded the Paul E. Strandjord Young Investigator Award from the Academy of Clinical Laboratory Physicians and Scientists in 2001 and 2002.

James C. Zimring, MD, PhD
Selective Induction of Allotolerance in Bone Marrow Transplantation

Zimring, assistant professor at Emory University School of Medicine’s Department of Pathology and Laboratory Medicine in Atlanta, Ga., plans to use the grant for a two-year study to develop methods to address a central problem of bone marrow transplantation (BMT). Unlike solid organ transplants in which the transplanted organ can be rejected by the recipient's immune system, in BMT the transplant itself has the capacity to attack the recipient tissues resulting in graft versus host disease (GvHD). Current methodologies for preventing GvHD result in a severe immunocompromised state of the transplant recipient that leads to significant morbidity and mortality from infections. Previous studies have shown that recipient blood contains CD8⁺

“veto” cells that are capable of preventing GVHD by donor T-cells. Such veto cells are theoretically capable of preventing GvHD without resulting in immunosuppression and thus represent a potential means to overcome a significant hurdle in human BMT. Using a murine (mouse) model of BMT and post-transplant infection with murine cytomegalovirus (mCMV), the current studies will address both mechanistic issues of veto cell function and practical issues of feasibility of utilizing this approach in clinical BMT in humans.

Zimring earned his bachelor’s degree, doctorate in immunology and medical degree from Emory University in Atlanta, Ga. He also completed his residency with a focus on clinical pathology and postdoctoral work in immunology while at Emory University. Zimring was appointed as a member of the Transfusion Medicine Program at Emory University School of Medicine in 2003, and as an assistant director in the Emory University Special Hemostasis Laboratory in the Department of Pathology and Laboratory Medicine in 2002. Zimring was awarded Best Medical Student Research Project by Emory University School of Medicine in 1994.

NBF scientific research grants are made possible by contributions from NBF’s Council on Research and Development (CORD) members and its NBF Partners, along with gifts from individuals, institutions and foundations. CORD members include Abbott Laboratories; Baxter Healthcare Corporation; Blood Systems/United Blood Services; Cerus Corporation; Chiron Corporation; Gambro BCT; Haemonetics Corporation; Ortho-Clinical Diagnostic’s, Inc.; Pall Corporation; Roche Diagnostic Corporation; and V.I. Technologies, Inc. (Vitex). NBF Partners include Blood Bank Computer Systems; Blood Centers of the Pacific; Bonfils Blood Center; Florida Georgia Blood Alliance; Global Med Technologies, Inc.; MacoPharma/United Pharma; Olympus America, Inc.; SEBRA; and The Blood Center of Southeastern Wisconsin, Inc.

About the National Blood Foundation
The National Blood Foundation (NBF), established in 1983, has a history of supporting research and education that advances transfusion medicine and blood banking to benefit both patients and donors.

About AABB
Established in 1947, the American Association of Blood Banks is an international association of blood banks, including hospital and community blood centers, transfusion and transplantation services and individuals involved in activities related to transfusion and transplantation medicine. AABB supports high standards of medical, technical and administrative performance, scientific investigation, clinical application and education. It is dedicated to encouraging the voluntary donation of blood and other tissues and organs through education, public information and research. AABB member facilities are responsible for collecting virtually all of the nation’s blood supply and transfusing more than 80 percent. Approximately 2,000 institutions (community and hospital blood banks, hospital transfusion services and laboratories) and 8,000 individuals are members of AABB, including physicians, scientists, administrators, medical technologists, blood donor recruiters and public relations personnel. Members are located in all 50 states and 80 countries.

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