Grants and Grant Recipients
Since 1989, AAMDSIF has provided research grants totaling in excess of $5.9 million to an international group of 107 researchers
The two-year grants have helped bring forth new insights into the causes and therapeutic approaches for these diseases. These grantee profiles present the grantees by year the awards were granted, and a summary of their grant-funded research projects.
Grant Year: 2015
Sicheng Wen, MD, PhD
Amy Gaynor Research Fund
Aplastic anemia is a potentially life-threatening bone marrow failure in which the body stops producing enough new blood cells. Marrow transplantation, antithymocyte globulin (ATG) treatment and other approaches can vary in effectiveness in approaching marrow aplasia. Extracellular vesicles are small particles released from cells that were initially thought to present cell “junk”, and later evaluated to be involved in cell-to-cell communication and affect the phenotype of target cells. In this study, we will evaluate the capacity of mesenchymal stem cell derived-extracellular vesicles (MSC-EV) to reverse aplasia in a murine model of aplastic anemia and identify the MSC-EV associated miRNA responsible for the reversal of aplastic anemia. This AA&MDSIF research grant will give us an...
Britta Will, PhD
Harold Spielberg Research Fund
Myelodysplastic syndromes (MDS) are the most common hematologic malignancies in the elderly, presenting as bone marrow failure and characterized by disorderly growth and differentiation of aberrant hematopoietic stem and progenitor cells. Bone marrow transplantation is currently the only curative option for MDS. Even though 5-azacitidine (5-aza) has resulted in clinical responses and improvements in overall survival, relapse and refractory disease continue to occur in some patients.
Recent findings show that cancer-initiating cells (CIC) can exist as pools of relatively quiescent cells that do not respond well to common cell-toxic agents and contribute to treatment failure. In fact, we and others have shown that karyotypically abnormal hematopoietic stem cells (HSCs) can survive during...
Grant Year: 2014
Daria Babushok, MD, PhD
Sam Jordan Research Fund, Stephen and Joanna Janowiak Research Fund, Torry Yahn Research Fund
Aplastic anemia (AA) is a devastating blood disorder, affecting children and adults, caused by immune attack on the bone marrow. Factors that determine recovery, relapse, and transformation to myelodysplasia in aAA remain poorly defined, and there is a dearth of studies in pediatric patients. Emerging data suggest that mutations in the bone marrow and in the pathogenic immune cells contribute to disease evolution and relapse. To study this, I will employ cutting-edge genomic techniques to characterize pathogenic mutations in aAA. These studies will improve treatment of patients with pediatric AA by allowing early detection of clonal evolution and disease progression.
Luis Batista, PhD
Bradley Richard Research Fund, Research is Hope Fund
Bone marrow failure is a serious condition that occurs when the bone marrow stops making enough healthy blood cells. A risk for bone marrow failure is genetic instability, including exacerbated shortening of telomeres (repetitive DNA sequences that cap chromosome ends). Using different genetic and biochemical approaches, this proposal will use cells derived from bone marrow failure patients that have telomere attrition as a platform for the development of clinical therapies against this disease. These experiments will increase our knowledge on stem cell function and regulation in bone marrow failure syndromes.
Rosannah Cameron, PhD
Lindsay Minelli Research Fund, Research is Hope Fund
We do not yet fully understand the process of disease progression in MDS. We know certain genes are involved because mutations in those genes have been found in MDS patients. We need to understand which genes are important early in the disease and which ones act later. Our goal is to identify the genes that act early in MDS, so that ultimately, our research will lead to new treatment options that are more specific and effective.
Youmna Kfoury, PhD
Lisa Lancaster Research Fund
Myelodysplastic Syndromes (MDS) are a group of diverse and incurable pre-leukemic disorders. Even though a deregulated bone marrow microenvironment is thought to participate in the disease, its role remains elusive. Since the microenvironment is better understood in mice, we have identified a subset of cells in the human bone marrow that is equivalent to those cells in mice which, when perturbed, lead to MDS. We propose to characterize these cells in patient samples at the cellular and molecular level. This will provide a better understanding of the abnormal signaling pathways involved in MDS, and eventually identify therapeutic approaches.
Patrizia Ricci, PhD
PNH Research and Support Foundation
PNH is a rare hematological disease characterized by spontaneous destruction of red blood cells (intravascular hemolysis), poor functioning of bone marrow, and thrombosis. Recently, the availability of the complement inhibitor eculizumab has dramatically improved the treatment of PNH. Nevertheless, about half of the patients treated with eculizumab shows a persistence of clinical signs of the disease. We have recently described the reasons underlying the limited efficacy of current anti-complement treatment for PNH. With this proposal we aim to complete the pre-clinical development of a novel complement inhibitor which targets early events in complement activation, the component-3 of the complement cascade.
Chao-Yie Yang, MD, PhD
PNH Research and Support Foundation
Uncontrolled complement activation caused by a gene (PIG-A) mutation in hematopoietic stem cells has been characterized in PNH. Patients suffer from hemolysis, thrombosis and bone marrow failure. Current FDA-approved only treatment for PNH is eculizumab which is expensive, unable to eradicate PNH clone, not orally available, requires clinic-bound infusions via iv access and lifelong therapy. In this proposed work, we will discover and make rational designs to small molecules guided by protein structures to develop complement inhibitors. The promising small molecule inhibitors identified from this work will be evaluated and used to develop orally-available therapeutics to treat PNH patients.
Grant Year: 2013
Andrew Dancis, MD
Research is Hope Fund
Myelodysplasia is a bone marrow failure syndrome with a
tendency to progress to leukemia. A characteristic finding in blood cell
precursors of some individuals with myelodysplasia is the ringed sideroblast, a
cell that accumulates large amounts of toxic iron in mitochondria. Recently, the
presence of these abnormal mitochondria has been correlated with mutations of
the splice factor SF3B1. We plan to investigate the mitochondria of these cells
with perturbed SF3B1, aiming to gain insight into mitochondrial causes of
myelodysplasia. This may point to new therapies.
Hideki Makishima, MD, PhD
PNH Research and Support Foundation
PNH is a disease in which a mutation
in the gene called PIG-A is acquired in the stem cells (mother cells of all
blood cells) in the bone marrow of patients.
As a result the blood cells produced by this stem cell are
defective. While previous discover of
the PIG-A gene mutation has helped to explain the symptoms in the disease, it
remains unclear how PIG-A mutation makes the PNH stem cells outcompete healthy
stem cells. In this project we propose
to apply a very efficient sequencing technology to examine all genes in PNH
stem cells to see whether additional mutations will explain how PNH
develops. In the initial experiments we
have identified such additional mutations.
They may help to devise treatments to eradicate PNH stem cells from the...