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: 2024
Brian Ball, MD
Hadi Abdur Rasheed Research Fund
Aplastic anemia (AA) is a type of bone marrow failure arising from autoimmune destruction of bone marrow stem cells. AA can occur at any age, however, the peak incidence is between 15-24 years. Among pediatric and adolescent/ young adult patients (aged < 40 years) with AA, somatic mutations are common, detected in ~20% of patients at diagnosis. The presence of high-risk somatic mutations in these patients have been associated with decreased responses to immunosuppressive therapy (IST), development of hematologic malignancies, and decreased overall survival (OS). Allogeneic hematopoietic cell transplantation (AlloHCT) is a potential curative approach for pediatric and AYA patients with AA; however, its use is limited by transplant-related complications, in particular graft vs. host...
Gloria Gerber, MD
Paroxysmal nocturnal hemoglobinuria (PNH) results from a mutation in the blood-forming stem cells. PNH blood cells are more susceptible to destruction by a part of the immune system known as complement. This can result in severe anemia, blood clotting, and many other symptoms that interfere with quality of life and can even be life threatening. Recently, there has been an expansion of different therapies to treat PNH. In addition to their various modes of administration (e.g., oral, intravenous, injection), these therapies target different proteins in the complement pathway. There is no available test to measure therapeutic levels of all these drugs and assess whether complement is fully blocked. This proposal will validate a test, called the bioluminescent modified Ham, that can monitor...
Parveen Shiraz, MD
Aplastic anemia and myelodysplastic syndrome are diseases that affect the bone marrow stem cells leading to failure of the bone marrow to produce normal blood and immune cells. These diseases are fatal if untreated. Donor bone marrow stem cell transplant (BMT) is the only cure for such bone marrow failure (BMF) conditions. However, graft versus host disease (GVHD) is a frequent side effect of BMT and can cause significant suffering and death. GVHD commonly affects skin, intestines, lungs, liver, eyes, and mouth. Success of BMT depends on successful treatment of GVHD. Treatment for GVHD involves immune suppressive medications which can also cause significant side effects. Early prediction of the severity of GVHD can be extremely helpful to adjust the doses of immune suppressive medications...
Ganesh Kumar Viswanathan, DM
Immune aplastic anemia (IAA) is a condition where the bone marrow doesn’t make enough blood cells, which can lead to low levels of red blood cells, white blood cells, and platelets. Although IAA is often seen as an immune problem, recent research shows that genetics might also be important, especially in certain groups of people, like those from Southeast Asia. Most studies on genetics have focused on small changes in genes, but they often miss larger genetic differences, especially in parts of the DNA that don’t directly code for proteins. Traditional methods for studying genetics might not catch these bigger changes. Newer technologies, like long-read sequencing from Oxford Nanopore, are better at finding these large variations. There is a pressing need to understand the genetic factors...
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...