2018 Grant Recipients
Arunoday K. Bhan, PhD
Postdoctoral Fellow, Pediatrics
Department of Hematology and Oncology
Boston Children’s Hospital
Identifying megakaryocyte maturation pathways critical for platelet generation
Immortalized hiPSC-derived MK progenitor cell lines (imMKCLs) can expand and produce platelets (plts) possess clinical plt production potential. However, it is functionally and phenotypically heterogeneous that limits its capability to generate plts. The proposed project would not only delineate maturation specific signaling pathways and associated genes that govern endomitosis and trigger plt release but also would generate a 2nd generation imMKCLs with better functionality and HLA I null plts.
Vijay G. Bhoj, MD, PhD
Postdoctoral Fellow, Pathology and Laboratory Medicine
University of Pennsylvania
Dissecting the Humoral Response to FVIII for Therapeutic Applications
Patients with Hemophilia A (HA), caused by a genetic deficiency of coagulation factor VIII (FVIII), suffer from life-threatening bleeding. Following FVIII replacement, the optimal treatment, 30% of patients develop anti-FVIII antibodies, which nullifies the therapy. This proposal is centered on (1) understanding fundamental features of the antibody response to FVIII in patients and (2) evaluating novel therapies aimed at eradicating such antibodies.
Avital Mendelson, PhD
Lindsley F. Kimball Research Institute
New York Blood Center
New York, NY
A biomimetic niche for platelet formation in vitro
Platelet transfusion can be life-saving for patients with severe thrombocytopenia but clinical demands are difficult to meet due to insufficient donor sources and limited shelf life. The development of new methods to promote platelet formation ex-vivo could significantly impact the prognosis of patients with blood disorders. Our goal is to develop a novel artificial niche that harbors the innate ability of co-existing niche cells and applied fluidic forces to promote platelet formation in vitro.
Antonella Nai, PhD
Regulation of Iron Metabolism Unit
Division of Genetics and Cell Biology
San Raffaele Scientific Institute
Targeting the second transferrin receptor for amelioration of severe malarial anemia
Our project is aimed at establishing the role of TFR2 on erythroid precursors in a murine model of malaria, in order to provide a new potential therapeutic intervention.
Robert S. Nickel, MD, MSc
Assistant Professor, Hematology
Children's Research Institute
Hydroxyurea and Transfusion (HAT): Pilot Study of Combination Therapy for Patients with Sickle Cell Anemia
Chronic red cell transfusions decrease stroke in sickle cell anemia (SCA) but may fail to prevent worsening cerebrovascular disease. Hydroxyurea, a disease-modifying medication for SCA, is not traditionally used with chronic transfusion. Combination hydroxyurea and transfusion may provide clinical benefits and decrease transfusion needs. We plan to investigate the feasibility, safety, and effect on transfusion requirements of combining hydroxyurea with simple chronic transfusion in SCA.
Hideyuki Oguro, PhD, MSc, BSc
Associate Director of Cellular Engineering
The Jackson Laboratory
Induction of hematopoietic stem cell proliferation and mobilization by estrogen receptor signaling
The demand for donor HSCs outreaches the supply in clinical transplantation. We have shown that treating mice with different estrogen receptor α (ERα) ligands induced HSC proliferation and mobilization. Here we propose to determine the impact of ERα ligands on improving mobilized HSC collection and regeneration after transplantation. We also seek to identify target genes of ERα that regulates HSC function. This study is anticipated to develop improved strategies for clinical HSC transplantation.
Moritz Stolla, MD, PhD
Director, Platelet Transfusion Research
Assistant Member, Bloodworks Northwest Research Institute
Assistant Professor, University of Wash. School of Med., Dpt. of Medicine, Div. of Hematology
Associate Medical Director, Swedish Medical Center
Cold-stored Platelets for the Reversal of Dual Antiplatelet Therapy
Cold-stored platelet (CSP, 4ºC) transfusions are approved by the FDA for the management of actively bleeding patients, but CSP transfusions have never been investigated for the reversal of dual antiplatelet therapy (DAPT). We propose to conduct a study in healthy human subjects receiving DAPT to test if autologous CSP transfusions are more effective than autologous room temperature-stored transfusions. We will assess platelet activation tests before, and serially after transfusion.