The National Blood Foundation (NBF) Board of Trustees recently announced the recipients of the 2010 NBF Scientific Research Grants. Each grant recipient will receive up to $75,000 to pursue either a one- or two-year research project in the field transfusion medicine and cellular therapy. To date, NBF has awarded more than $6.6 million in grants since 1985 to 165 early-career researchers. This year's recipients are: Julie Audet, PhD; Rachel Bercovitz, MD; Jonathan Finn, PhD; Peter Ghoroghchian, MD, PhD; Mariluz Mojica Henshaw, PhD; Jill Johnsen, MD; Bartolomeu Nascimento, MD and Sergey Shevkopyas, PhD.
"The funding from NBF's research grant program is key to supporting early career researchers as they explore diverse, cutting edge topics that will contribute to the further advancement of transfusion medicine and cellular therapy worldwide," said Connie Westhoff, PhD, chair of NBF's Grants Review Committee. "This program serves an important role in support of research and is the only grant program that directly focuses on professionals in the transfusion medicine and cellular therapy community. We are very pleased by the quality of research that will be performed, and applaud the awardees for their innovative research approaches to advancing transfusion medicine."
Proposals for NBF grants are evaluated on the basis of their scientific merit; relevance to and impact on transfusion medicine and cellular therapy field. NBF scientific research grants are made possible by contributions from NBF's Council on Research and Development (CORD) members along with gifts from individuals, institutions and foundations.
The following are synopses of the funded proposals:
Julie Audet, PhD, University of Toronto
Directed Expansion and Differentiation of Blood Progenitor Cells using TAT-Conjugated Transcription Factors
With the demand for blood frequently changing, one possible alternative is the production of red blood cells in culture in the laboratory. To achieve this goal, however, methods must be found to increase the yield of hematopoietic stem and progenitor cells and to ensure their differentiation into Red blood cells. Audet and her colleagues will investigate the possibility of using transcription factors to accomplish these goals.
Rachel Bercovitz, MD, The University of Colorado Denver, Dept. of Pediatrics
Transfusion-related Acute Lung Injury (TRALI) from Plasma Products: Understanding the Pathogenesis of Immune- and Non-Immune-Mediated TRALI and Determining Methods to Mitigate TRALI Risk
Contamination of fresh frozen plasma with platelets may lead to transfusion-related acute lung injury in patients. Most risk-reduction efforts to date have concentrated on deferring certain blood donors to minimize the risk of immune-mediated TRALI. Bercovitz and her colleagues hope to expand these mitigation efforts to include nonimmune-mediated TRALI using manufacturing techniques.
Under the NBF grant, the researchers will quantify the platelet and platelet-derived contaminants in plasma units licensed by the FDA, document their accumulation during storage, attempt to determine the roles these contaminants play in TRALI and identify screening protocols for donor blood products to reduce the risk. The ultimate goals are to get a better idea of the pathophysiology of TRALI and to find inexpensive and easy processing steps that could mitigate TRALI risk.
Jonathan Finn, PhD, Children's Hospital of Philadelphia
The Development and Safety Characterization of Novel Hyper-functional Factor IX Variants for the Treatment of Hemophilia B
Hemophilia B is a bleeding disorder caused by decreased activity of coagulation factor IX, or FIX. The treatment of hemophilia B currently depends on infusion of FIX from plasma-derived or recombinant sources; the expense of these therapies prohibits their prophylactic use.
Finn and his colleagues recently described a mutation in a patient's factor IX gene that resulted in an eightfold increase in FIX activity levels. With their NBF grant, the researchers will characterize the activity and the safety of variants in the factor IX gene with the ultimate aim of finding more effective therapies for hemophilia B.
Peter Ghoroghchian, MD, PhD, University of Pennsylvania
Fundamental Design and Characterization of Nanoscale Polymersomes as Advanced Hemoglobin-based Oxygen Carriers
Another alternative blood product is proposed by Ghoroghchian and co-workers - the development of an oxygen carrying blood substitute. The major goal of this project is to develop polymersomes as an artificial blood substitute that could be administered to any patient, especially under emergency conditions, to help circumvent the need for blood typing and matching. This new blood substitute, called 'NanoHeme,' has the potential for long storage times, would be available in the field and could immediately be infused into the trauma patient to provide oxygen-carrying capacity for 24 to 36 hours.
Mariluz Mojica Henshaw, PhD, University of Utah, Cell Therapy Facility
Development of a Xeno-free Microcarrier-based Human Mesenchymal Stem Cell Expansion System
Human bone marrow-derived mesenchymal stem cells, or MSCs, have shown potential utility in clinical trials in several areas of regenerative medicine. However, their production in culture, traditionally using media supplemented with fetal bovine serum, or FBS, carries with it the risk of exposure to foreign proteins and the possible contamination with infectious agents inherent in prolonged exposure to animal-sourced media. Recent studies suggest that a potentially comparable or superior substitute to FBS may be platelet lysate, which is rich in growth factors known to enhance MSC expansion. With the support of an NBF grant, Mojica Henshaw and colleagues propose to optimize the process for preparation of platelet lysate. Currently there is no standardized protocol for preparing platelet lysate or characterization of the resulting product. An optimized expansion culture protocol using a three-dimensional microcarrier-based scaffold to increase yield of MSCs would benefit clinical researchers.
Jill Johnsen, MD, Puget Sound Blood Center and University of Washington
The Role of Blood Group Antigens in Von Willebrand Factor Homeostasis
Levels of the coagulation protein von Willebrand factor, or VWF, are widely variable in humans. The glycoprotein plays an important role in hemostasis: deficiencies in VWF result in von Willebrand disease, an inherited bleeding disorder, and high levels are associated with increased risk of thrombosis. About one-third of the variability of VWF levels can be attributed to environmental or acquired causes; the rest stem from genetic factors. Blood group antigens are the only inherited factors identified so far that influence VWF levels. Johnsen and co-workers propose to study two mouse knockout models of human blood groups known to have an effect on VWF levels in humans.
Bartolomeu Nascimento, MD, Sunnybrook Health Sciences Centre, Toronto
Trauma Resuscitation Formula-driven versus Laboratory-guided Transfusion Study (TRFL): Coagulopathy Substudy
The main causes of hospital death among patients in the early hours after trauma are bleeding and coagulopathy. The mechanisms leading to coagulopathy are poorly understood, but it follows major blood loss and replacement with crystalloid and red blood cell transfusion. The goal of this research is to understand coagulation in the early stages of bleeding in trauma patients. Nascimento and colleagues propose to assess the coagulation status of patients enrolled in an ongoing clinical trial. Using sophisticated tests to measure all the clotting factors and biological markers of coagulation, Nascimento wants to determine what is happening in the physiology of trauma patients: Besides blood loss, what is causing the coagulopathy? Does the injured tissue release biomarkers that cause it?
A better understanding of coagulopathy could lead to the development of improved management strategies for patients arriving at the emergency room.
Sergey Shevkopyas, PhD, Tulane University, Biomedical Engineering
The Relationship between the Ability of Stored Red Blood Cells to Perfuse Microvascular Networks and their 24-hr Post-Transfusion Recovery in Vivo
The quality of red blood cells in storage can deteriorate as the cells lose certain functional abilities and accumulate oxidative damage over time. This "storage lesion" decreases the ability of red blood cells to deliver oxygen effectively in the transfusion recipient.
With the NBF grant, Shevkoplyas and colleagues will assess the ability of artificial microvasculature networks, or AMVNs, to detect the deterioration in red blood cells that takes place over time. They plan to compare the behavior of stored red blood cells in AMVNs with the 24-hour in vivo recovery of transfused blood in human subjects.
About 2011 Scientific Research Grant Applications
NBF is currently accepting scientific research grant applications. Grant applications are available on the NBF Web page. Applications must be received by December 30, 2010. Grant awards will be announced in June 2011. NBF, a program of AABB that was established in 1983, is dedicated to advancing transfusion medicine, cellular therapies, and blood banking by funding scientific research that benefits patients and donors.
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