2019 Grant Recipients
Delfim Duarte, MD, PhD
Instituto de Biologia Molecular e Celular (IBMC)
"Targeting the Bone Marrow Vascular Microenvironment to Improve Hematopoietic Stem Cell Therapies in Acute Myeloid Leukemia"
Allogeneic hematopoietic stem cell (HSC) transplantation remains the only curative treatment for most cases of refractory/relapsed Acute Myeloid Leukemia (AML). Endosteal blood vessels maintain HSCs. We have recently described a specific remodeling/decay of endosteal blood vessels in AML. We aim to specifically target the BM vascular microenvironment in AML and in this way improve HSC engraftment, promote cell competition and eliminate AML cells, ultimately leading to improved disease outcomes.
Saba Ghassemi, PhD
Associate Research Scientist
Pathology and Lab Medicine
University of Pennsylvania
"Redirecting Quiescent T cells with Chimeric Antigen Receptors (CARs) for Adoptive Immunotherapy"
Chimeric antigen receptors (CARs) provide a promising approach to redirect T cell specificity against cancer. Activation of the T cell receptor (TCR) is a prerequisite for effective CAR transduction. TCR activation promotes progressive differentiation which limits CAR T cell engraftment and persistence. This proposal focuses on transducing quiescent T cells. I will determine how CAR co-stimulation and T cell composition influences efficacy when quiescent T cells are used as therapy.
Marie Hollenhorst, MD, PhD
Hematology Fellow and Chemistry Postdoctoral Fellow
"CMP-Neu5Ac: A Central Molecule in Bleeding Diseases and Mediator of a Novel Platelet Effector Function"
Platelets are critical to the pathogenesis of some of the most important causes of morbidity and mortality worldwide, including hemorrhage, heart attack, and stroke. The aim of the proposed research is to understand how a sugar molecule called CMP-Neu5Ac is made and how it is used to regulate platelet number and function. This work will illuminate fundamental aspects of platelet biology and will pave the way for development of effective therapies for bleeding and clotting disorders.
Tiffany Thomas, PhD
Department of Pathology and Cell Biology
Columbia University Medical Center
New York, NY
"The Effect of Dietary Lipids on Red Cell Lifespan and Recovery"
Our underlying hypothesis is that increasing dietary omega-3 PUFAs up to a threshold improves RBC lifespan and PTR; but, increasing omega-3 PUFAs above this threshold decreases quality. The inflection point will be a function of oxidative stress and antioxidant capacity. As such, conditions of elevated oxidative stress (e.g. SCD) will lower the observed fish oil dose associated with this inflection point due to increased lipid peroxidation, resulting in decreased endogenous RBC lifespan and PTR.
Francesca Vinchi, PhD
Iron Research Laboratory
New York Blood Center
New York, NY
"Role of Heme-Activated Macrophages in Acute Chest Syndrome"
Our project focuses on the role of heme-activated macrophages in the pathophysiology of acute chest syndrome (ACS), a major complication of SCD. We hypothesize that by mediating lung macrophage inflammatory phenotypic switching, heme promotes ACS and exacerbates symptoms in response to infections/fat emboli. Using SCD and ACS mouse models, we plan to investigate the cellular and molecular mechanisms underlying ACS and whether transfusion and novel cellular therapies can mitigate the syndrome.
Yan Zheng, MD, PhD
St. Jude Children's Hospital
"Comprehensive Characterization of RH Loci by Whole Genome Sequencing and Long-read Genome Sequencing"
RHD and RHCE genes exhibit extensive nucleotide polymorphism and genetic rearrangements, resulting in the formation of Rh variant antigens. Therefore, sickle cell patients harboring Rh variants are predisposed to Rh alloimmunization despite receiving serologic Rh antigen-matched blood. We aim to develop novel approaches to more accurately and comprehensively characterize the RH loci using whole genome sequencing and long-read sequencing data.