Grants and Grant Recipients
For over 30 years, AAMDSIF has provided research grants totaling in excess of $5.5 million to an international group of more than 100 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.
Grant Year: 2023
Carlos Bravo-Perez, MD, PhD
Patricia and Vincent Geczik Legacy Fund
Autoimmunity and immunodeficiency can coexist. Inborn errors of immunity are a heterogeneous group of genetic disorders in which the immune system is disturbed, not only affecting its ability to combat pathogens, but also to trigger autoimmunity. Despite early-onset and severe disease being expected for these disorders with the advent of modern DNA sequencing technologies, an increasing number of adult-onset errors of immunity has been identified. With this proposal, we aim to assess the presence of inherited gene variants predisposing to immunodeficiency as determinants of PNH and AA. First, to increase the power of our pilot study and validate our results, we will additionally perform genome sequencing to analyze an overall cohort of 250 PNH/AA patients (100 with PNH and 150 with AA)....
Kohei Hosokawa, MD, PhD
Acquired aplastic anemia (AA), the prototypical bone marrow (BM) failure syndrome, is caused by immune-mediated destruction of hematopoietic stem/progenitor cells (HSPCs). An immune mechanism was inferred decades ago from the recovery of hematopoiesis in patients who failed to engraft after stem cell transplantation, when renewal of autologous blood-cell production was credited to the conditioning regimen. The responsiveness of AA to immunosuppressive therapy (IST) in most patients is the best evidence of an underlying immune pathophysiology: the majority of patients show hematologic improvement after transient T-cell depletion by ATGs. The key goal of this project is to identify autoantigens presented by HLA molecules in AA patients using induced pluripotent stem cells (iPSCs)...
Simone Feurstein, MD
Harold Spielberg Research Fund
This research project aims to understand the biology and genetics of the disease myelodysplastic syndrome (MDS) in young patients. MDS is normally a disease of older persons (70+), and this study aims to determine the genetics and biology of MDS in patients diagnosed between the ages of 18 and 40 years old. MDS in young people is a distinct population with a lot of different genetic problems causing illness, most being related to the cell's repair of DNA and parts of the chromosomes. Autoimmune and inflammatory conditions are common in MDS patients and are associated with failures in the bone marrow - a part of the body responsible for making blood cells. However, how common, and how seriously these mutated genes affect patients is unknown. This study will look at the entire genetic...
Grant Year: 2022
David Beck, MD, PhD
Harold Spielberg Research Fund
Acquired bone marrow failure syndromes, such as myelodysplastic syndrome (MDS), are frequently caused by genetic mutations. Both the underlying mechanism and prognosis of MDS have been attributed to specific driver gene mutations, and genetic classification systems have led to improved clinical outcomes. Bone marrow failure, and MDS have been linked to autoimmune diseases although the clinical relevance of these associations has not been well defined. We identified an acquired mutation in the gene UBA1 that occurs in the earliest progenitors in the bone marrow, and leads to common inflammatory rheumatic and hematologic diseases such as rheumatoid arthritis and myelodysplastic syndrome. Patients with mutations in UBA1 have VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic)...
Sushant Kumar, PhD
PNH Research and Support Foundation
Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare blood disease in which blood cells are destroyed, leading to anemia, fatigue, and increased risk of blood clots. While several effective therapies can prevent the destruction of PNH red blood cells by blocking abnormal activation of a part of the immune system called “complement”, these treatments are life-long, extremely costly and do not lead to cure. In many places around the world, access to PNH treatments is limited. The main barrier to developing curative therapies for PNH has been a poor understanding of why PNH patients develop large outgrowths (“clones”) of PNH cells. Interestingly, most healthy individuals also harbor a few, very rare, isolated PNH cells, but these do not outgrow normal cells and do not turn into PNH clones,...
Grant Year: 2021
Salima Benbarche, PhD
Harold Spielberg Research Fund
We discovered a way to express a gene or protein of interest in cancer cells, but not healthy normal cells. Specifically, we created synthetic (not occurring in nature) introns that we can introduce into any gene of interest, such as a “killer gene,” such that the encoded protein is produced in cancer cells carrying a defined, cancer-causing mutation, but not produced in healthy normal cells that do not carry that specific mutation. These types of cancer-causing mutations are mainly identified in patients with myelodysplastic syndromes, a group of cancers in which immature blood cells in the bone marrow do not mature or become healthy blood cells. We believe that these synthetic introns will enable the development of new cancer therapeutics that are highly specific to cancer cells while...
Sushree Sahoo, PhD
Emily Kass Research Fund
Myelodysplastic syndrome (MDS) in children is a rare group of disorders in which blood-making stem cells in the bone marrow (BM) fail to work properly. As a result, patients develop low blood counts and have increased risk to develop leukemia with cancerous cells, referred to as blasts, also called refractory cytopenia of childhood (RCC). Although RCC is the most common category, we do not fully understand its molecular basis (gene and chromosome changes associated with the disease). Some patients with RCC have empty BM which might be mistaken for aplastic anemia, while others have acquired changes that predispose them to more advanced MDS and leukemia. Therefore, it is often difficult to tell apart RCC from other blood disorders such as inherited marrow failure or acquired aplastic...
Grant Year: 2020
Valentina Giudice, MD
Amy Gaynor Research Fund
Circulating low-density granulocytes (LDGs) are a subgroup of neutrophils with immunoregulatory functions which can spontaneously release extracellular web-like structures (NETs) and cytokines sustaining T cell responses and dendritic cell activation. We hypothesize that LDGs and NETs might be impaired in functions and frequency during myelodysplastic syndromes (MDS) and acquired aplastic anemia (AA) and might contribute to the suppression of hematopoietic stem cell proliferation and differentiation. We aim at investigating over a 12 month period the frequency and functions of LDGs and NET formation and composition in MDS and AA at diagnosis and during treatments. Moreover, the number of LDGs and NET levels will be correlate to other markers of inflammation and genomic alterations. This...
Audrey Lasry, PhD
Harold Spielberg Research Fund
Myelodysplastic syndrome (MDS) is a pre-cancerous disease of the blood, which progresses to the more aggressive acute myeloid leukemia (AML) in approximately 30% of cases. MDS currently affects about 60,000 people in the US, and about 10,000 new cases are diagnosed each year. Life expectancy for MDS patients ranges from 5 months to 3 years, yet therapeutic options for MDS patients are limited.
In recent years, advances in understanding of the immune system have led to a major breakthrough in cancer therapy, with the development of immunotherapy drugs that target the immune system rather than the cancer cells. These drugs are effective in many types of cancer, and have revolutionized treatment for cancers that were often considered untreatable in the past. The effectiveness of...
Grant Year: 2019
Jill de Jong, MD, PhD
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...