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Chou (CHOP) Research Hub 02

Stella Chou, MD

U01 Principal Investigator, 1-U01HL134696-01

Improving Transfusion Therapy for Patients With Sickle Cell Disease With Pluripotent Stem Cell-Derived Red Cells

Red blood cell transfusion remains a life-saving therapy for patients with sickle cell disease (SCD). A major problem is the high rate of alloimmunization (antibody formation against transfused red cells) that occurs in transfused patients with SCD. Genetic diversity in blood group antigens in patients of African descent compared to the primarily European-based donor pool contributes to this high incidence and complexity of antibodies found in patients with SCD. Finding compatible red blood cell (RBC) units is often complicated by a lack of rare reagent RBCs to properly identify these complex antibody specificities. This complication delays care, increases costs, and makes transfusion therapy impossible for some patients. The ultimate goal of this proposal is to use human induced pluripotent stem cells (iPSCs) to produce standard and reliable red blood cell (RBC) reagents to resolve this major problem. We have designed a panel of iPSCs genetically engineered to express unique combinations of blood group antigens (customized iPSCs) that are difficult or virtually impossible to find in donor RBCs. RBC reagents produced from these customized iPSCs will provide the means to streamline and standardize antibody identification in alloimmunized patients, and ultimately can be used as “universal” donor cells for future therapeutic applications. Our efforts will address several existing challenges that include: i. insufficient or no living blood donors expressing the combinations of blood group antigens needed to resolve the complex antibody specificities in patients with SCD, ii. lack of iPSC differentiation protocols to produce definitive, adult-type RBCs without the use of serum or stromal cells, and iii. the prohibitively expensive manufacturing costs of iPSC-derived RBCs. In this U01 application, we propose three integrated Projects from a group of highly collaborative investigators with expertise in areas that can address all three challenges and will drive the field forward by providing innovative solutions to these current obstacles.

members: 
Lead Principal Investigator
User Name Full Name Institute Affiliation Topic tags People tags
schou's picture
schou Stella Chou, M.D. The Children's Hospital of Philadelphia
Co-PI/Co-Investigator
User Name Full Name Institute Affiliation Topic tags People tags
dfrench's picture
dfrench Deborah French, Ph.D. Children's Hospital of Philadelphia
pgadue's picture
pgadue Paul Gadue, Ph.D. Children's Hospital of Philadelphia
gkeller's picture
gkeller Gordon Keller, PhD Toronto Medical Discovery Tower
jpalis's picture
jpalis Jim Palis, MD University of Rochester Medical Center School of Medicine and Dentistry
cwesthoff's picture
cwesthoff Connie Westhoff, SBB, PhD National Center for Blood Group Genomics
Post-Doctoral Fellow/Trainee
User Name Full Name Institute Affiliation Topic tags People tags
HAan's picture
HAan Hyun Hyung An The Children's Hospital of Philadelphia
Sborst's picture
Sborst Sara Borst University of Pennsylvania
JAolsen's picture
JAolsen Jayme L Olsen M.Sc. University of Rochester Medical Center
soroushf13's picture
soroushf13 Fariborz Soroush, Ph.D. Children's Hospital of Philadelphia
kstewart's picture
kstewart Kathleen Stewart UPENN
Affiliated Investigator
User Name Full Name Institute Affiliation Topic tags People tags
jaeschlimann's picture
jaeschlimann Judith Aeschlimann New York Blood Center
flake.aw's picture
flake.aw Alan Flake, MD CHOP
khigh's picture
khigh Kathy High CHOP
kemcgrath's picture
kemcgrath Kathleen McGrath Ph.D. University of Rochester Medical Center
NAmruta's picture
NAmruta Dr. Amruta Naik CHOP
gpavani's picture
gpavani Giulia Pavani CHOP
SSengupta's picture
SSengupta Shaon Sengupta CHOP
Publication: 
Author(s) Title Link
Uter S, An HH, Linder GE, Kadauke S, Sesok-Pizzini D, Kim HC et al Measures to Reduce Red Cell Use in Patients with Sickle Cell Disease Requiring Red Cell Exchange During a Blood Shortage view
Zhang Z, An HH, Vege S, Hu T, Zhang S, Mosbruger T et al. Accurate Long-read Sequencing Allows Assembly of the Duplicated RHD and RHCE Genes Harboring Variants Relevant to Blood Transfusion view
Seu KG, Trump LR, Emberesh S, Lorsbach RB, Johnson C, Meznarich J et al VPS4A Mutations in Humans Cause Syndromic Congenital Dyserythropoietic Anemia due to Cytokinesis and Trafficking Defects view
Zheng Y, Chou ST Transfusion and Cellular Therapy in Pediatric Sickle Cell Disease view
Chia-Min Liao,1,2 Somdutta Mukherjee,2 Amita Tiyaboonchai,2 Jean Ann Maguire,1,2 Fabian L. Cardenas-Diaz,1,2 Deborah L. French,1,2 and Paul Gadue1,2 GATA6 Suppression Enhances Lung Specification from Human Pluripotent Stem Cells view
Sarah K. Tasian, Jessica A. Casas, Stella Chou Mutation-Specific Signaling Profiles and Kinase Inhibitor Sensitivities of Juvenile Myelomonocytic Leukemia Revealed by Induced Pluripotent Stem Cells view
Highly Efficient CRISPR-Cas9-Mediated Genome Editing in Human Pluripotent Stem Cells view
Cure P, Bembea M, Chou S, Doctor A, Eder A, Hendrickson J, Josephson CD, Mast AE, Savage W, Sola-Visner M, Spinella P, Stanworth S, Steiner M, Mondoro T, Zou S, Levy C, Waclawiw M, El Kassar N, Glynn S, Luban NL. 2016 proceedings of the National Heart, Lung, and Blood Institute's scientific priorities in pediatric transfusion medicine. view

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