Grant Recipients

For nearly 30 years, AAMDSIF has provided research grants totaling in excess of $5 million to an international group of more than 90 researchers to help advance the understanding and treatment of aplastic anemia, myelodysplastic syndromes (MDS), and paroxysmal nocturnal hemoglobinuria (PNH).

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.

Research Fund

Grant Year: 2019

Christin DeStefano, MD

The National Academy of Sciences Engineering and Medicine’s (NASEM) Veterans and Agent Orange (AO) Committees have been performing biennial reviews of the literature examining the relationship between AO exposure and the risk for adverse health outcomes since 1996. In 2018, the committee concluded there are sufficient data to associate AO exposure with an increased risk of Hodgkin and non-Hodgkin lymphoma, chronic lymphocytic leukemia, monoclonal gammopathy of unknown significance, and hypertension. In 22 years of follow up, there is only one paper addressing myelodysplastic syndrome (MDS) and none addressing aplastic anemia (AA) or myeloproliferative neoplasms (MPNs). The under representation is likely multifactorial, but low incidence is likely a major factor. This conundrum, lack of...

Elissa Furutani, MD

Julia Malsin Research Fund

Aplastic anemia is a rare but serious blood disorder that occurs when the body’s bone marrow cannot produce enough healthy blood cells to function properly. Aplastic anemia can be classified as moderate, severe or very severe, depending on stability of blood cell count and other symptoms. Most cases of aplastic anemia are idiopathic, meaning the underlying cause is unknown. Aplastic anemia can be due to inherited (genetic) causes in a minority of cases. Although many patients with genetic causes of aplastic anemia will present with more moderate blood counts initially and may have a family history of blood disorders and other physical findings associated with these genetic disorders, some patients may not have any of these findings. It is not currently known how many patients who present...

Grant Year: 2018

Eunice Sindhuvi Edison, PhD

Liviya Anderson Research Fund

Androgens have been used alone or in combination with other immunosuppressive therapy in aplastic anemia with inconsistent responses being reported. However, the exact mechanism of action of androgens is not known. Recent studies have shown that it tends to protect from telomere shortening in haematopoietic tissues by increasing telomerase activity. In addition, androgens exert various biological effects on both haematopoietic cells and stromal cells. Androgen receptors are found to be expressed on stromal cells, macrophages, endothelial cells, myeloblasts, myelocytes, neutrophils, and megakaryocytes. Androgens also have a suppressive effect on the immune system. Shortened telomeres in aplastic anemia were initially attributed to stress factors but was later recognized that telomere...

Valeria Visconte, PhD

Patricia and Vincent Geczik Legacy Fund

Paroxysmal nocturnal hemoglobinuria (PNH) is a stem cell disorder caused by a mutation in a gene called phosphatidylinositol glycan anchor biosynthesis class A gene (PIGA). PIGA produces a protein important in the formation of a group of proteins called glycophosphatidylinositol anchored proteins (GPI-AP). GPI-AP are attached to the cell membrane via a small anchor. Among them CD59 and CD55 are major targets for therapy. Due to PIGA mutation, PNH cells fail to synthesize a correct anchor and thereby lack of proper GPI-AP. To date, the drug developments for PNH have focused on supportive therapies to improve hemoglobin levels due to hemolysis or prevent thrombotic complications. Most successful to date were complement blockers designed for alleviation of hemolysis due to deficiency in...

Sydney Lu, MD, PhD

Harold Spielberg Research Fund

Recurrent change-of-function mutations in RNA splicing factors are frequent in patients with myelodysplastic syndromes (MDS) and related myeloid neoplasms. Splicing factor mutations most typically occur as heterozygous mutations at recurrent ‘hotspots’ along the amino acid sequence and in a mutually exclusive manner with one another. Although much remains to be learned about how these mutations promote MDS development, recent results from our lab and others have demonstrated that cells expressing these mutations are preferentially sensitive to further alterations to the RNA splicing process. Exploiting the selective vulnerability of splicing factor mutated myeloid neoplasms to further splicing inhibition has led to clinical development of drugs targeting...

Isabel Mérida, PhD

Mary Pat Madden

Aplastic anemia is a disease in which the bone marrow gradually stops producing red and white blood cells and platelets. As a result, people with aplastic anemia feel tired, may bleed more easily and are at higher risk of having infections. Aplastic anemia can strike at any age but is more often diagnosed in children, young adults and older people. In a few cases aplastic anemia is passed from parents to their child, but most often this disease results from destruction of the cells in the bone marrow by overactive immune system blood cells called T-cells. Healthy T cells are "trained" to recognize and destroy exclusively foreign invaders of the body, such as viruses. But in some cases, T cells attack the cells from the body, causing autoimmune diseases like lupus or rheumatoid arthritis...

Grant Year: 2017

Coleman Lindsley, MD, PhD

Harold Spielberg Research Fund

Myelodysplastic syndrome (MDS) is a diverse group of bone marrow diseases, unified by poor blood counts and a propensity for development of acute leukemia. MDS is most often diagnosed in older adults, arising as part of aging and without a toxic exposure or predisposing medical condition. In rare cases, however, MDS develops as a complication of an inherited bone marrow disease, such as dyskeratosis congenita, which causes a defect in telomere maintenance and have an increased risk of developing MDS and leukemia. Telomeres are caps that protects the ends of chromosomes from deterioration, and are important for preventing premature cellular aging. In preliminary studies in a large international cohort of MDS patients, we found that an unexpectedly high number of MDS patients have inherited...

Joseph Oved, MD

James D. Moreland Research Fund, Mary Pat Madden

Aplastic Anemia is a disease that results in the destruction of hematopoietic stem cells in the bone marrow by the immune system. Although the exact mechanism of this pathology is not fully understood, the prevailing model proposes that the immune system and specifically T cells are responsible for this destruction. Pediatric and adult aplastic anemia, while clinically similar in their presentation may in fact be representative of different subsets of a spectrum of aplastic anemia. Our group and others have shown that adult patients with aplastic anemia have a tendency to develop cell populations that are predisposed to myelodysplastic syndrome and leukemia. In the pediatric population however, we found that patients tend to develop cell populations that have mutations in certain genes (i...

Sergei Vatolin, PhD

Patricia and Vincent Geczik Legacy Fund

Medicines available to the patients with severe blood diseases like aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH) are very limited. The idea of improvement the quality of blood cells with small molecules may give a new opportunity to cure AA and hope to reverse PNH. Our proposal is based on discovery of drugs (TCC1 and TCC2) which improve performance of blood stem cells by increasing their life span. We hypothesize that the unique biological activity of these agents can already be used in clinic to treat AA and PNH by restoration the function of damaged/exhausted blood stem cells. Such effects may help to alleviate diseases and accelerate recovery of normal blood in patients with AA or PNH. The objective of this study is preclinical testing of the identified drugs to...

Grant Year: 2016

Akihide Yoshimi, MD, PhD

Shirley and James O’Brian Research Fund

Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders characterized by inefficient blood production. MDS represents the most common cause of acquired bone marrow failure in adults and there are few effective therapies for the majority of MDS patients. In 2011, it was discovered that mutations in proteins encoding RNA splicing factors (SFs) are the most common class of mutations in patients with MDS and chronic myelomonocytic leukemia (CMML). Despite these discoveries, however, we do not yet fully understand why abnormal RNA splicing results in MDS nor do we have therapies that specifically target MDS cells bearing this common class of mutations. The goals of this proposal are two-fold: (1) to determine the efficacy of clinical-grade novel spliceosome inhibitors in...

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