CAF Awards $227,500 Funding in Medical Research Fellowships

CAF is pleased to announce that five new Cooley’s Anemia Foundation Medical Research Fellowships and two renewal Fellowships have been awarded for the 2018-2019 grant cycle. The total amount of funding for the 7 research Fellowships is $227,500.

These Fellowship recipients were assessed on the basis of the quality of the scientific content, the academic accomplishments and future promise of the investigator, the quality of the mentor in the case of postdoctoral fellowships, and, of particular importance, the relevance of the project to the understanding and treatment of Cooley’s anemia. The CAF Grant Review Committee reviewed all applications carefully while adhering to the highest standard for scientifically un-biased reviews and made its recommendations for funding to the CAF Board of Directors, who approved those recommendations at its annual Board meeting.

We thank Dr. Janet Kwiatkowski, Chair of the CAF Grant Review Committee and Medical Advisory Board, and the other members of the Grant Review Committee for carefully reviewing the grant applications and making these important recommendations. We are excited to see what the investigators learn in these important and cutting-edge experiments.

First-Year Fellows

Annamaria Aprile, PhD, of the Fondazione Centro in San Raffaele, Italy will examine hematopoietic stem cells (HSC) and their vascular niches in mice that exhibit properties typical of human beta-thalassemia. Her preliminary studies indicate that HSC in these thalassemic mice fail to self-renew and that this might be the result of a defect in the progenitors in the niche. Competitive transplants, including serial transplants, using thalassemic vs wild type HSC will reveal whether or not HSC exhaustion is autonomous or is due to the signals they are receiving from their surrounding damaged environment in the niche. These experiments have the potential to be extremely revealing of the underlying mechanisms that influence HSC and early progenitor activity in thalassemia, and why this altered marrow leads to ineffective red cell production.

Chia-Yu Wang, PhD, of Massachusetts General Hospital will continue her work to identify the exact mechanism by which erythroferrone exerts its effect on iron regulation. When iron overload is present in patients with thalassemia, the increased red cell production in the bone marrow triggers the release of erythroferrone, which signals the cells in the bowel and elsewhere to absorb and release even more iron. Identification of the mechanism by which erythroferrone signals its effect has the potential to lead to a new therapeutic approach to the management of iron overload in thalassemia.

Divya Vinjamur, PhD, of Boston Children’s Hospital will investigate the role of the microtargetome, in particular the let-7 family of microRNAs (miRNAs), in fetal hemoglobin repression in adult erythroid cells. Identification of let-7 target genes that are effectors of HbF repression is a new approach that will likely identify a new set of proteins whose globin-regulating activities can be therapeutically modified. Elevation of fetal hemoglobin in adult erythrocytes as a therapeutic strategy for beta-thalassemia is a promising area of research.

Raman Bahal, PhD, of the University of Connecticut, will test an innovative approach to gene therapy by injecting thalassemic mice with nano-particles containing advanced molecules which allow short segments of DNA to enter and fix thalassemia mutations. Dr. Bahal previously injected such nano-particles into thalassemic mice, resulting in improved anemia and smaller spleens. In continuation of this work, Dr. Bahal will test an improved set of molecules in order to have an even greater impact. If successful, this could lead to thalassemia being cured by a series of injections without any intense chemotherapy to wipe out a patient’s marrow.

Yvette Yien., PhD, of University of Delaware will be leading a study to better define key pathways leading the heme synthesis in red blood cell development. Dr. Yien’s research group will utilize an innovative combination of iron/heme biochemistry, erythroid and yeast culture and mouse and zebrafish animal models to identify the detailed mechanisms of iron transport. Knowledge gained through this study will be especially important in cases when red blood cell development is abnormal, as is the case with thalassemia.

Second-Year Renewal Fellows

Antonella Nai, PhD, of San Raffaele University in Milan, Italy will continue her study focused on understanding the role of TfR2 in red cell production and control of iron in thalassemia. Dr. Nai has shown that inhibiting TfR2 activity in thalassemic mice significantly improves anemia, ineffective red cell production, and iron-overload in a mouse model of thalassemia intermedia. This year, she will test the effect of TfR2-antisense oligonucleotides as selective inhibitors of TfR2 to propose as a novel therapeutic agent for beta-thalassemia intermedia. She will also generate and analyze a model of thalassemia major with red-cell specific deletion of TfR2 in order to verify whether inactivation of TfR2 may be beneficial in the most severe form of the disorder.

Lei Yu, PhD, of University of Michigan Medical School will be continuing his study focusing on development of a small molecule analog to inhibit the activity of a repressor complex of fetal globin expression. Over the past year. Dr. Yu has made substantial progress by identifying a promising molecule. This year, he will modify the molecule to further improve efficacy and will continue to investigate the mechanism of gamma globin induction. This study will bring this molecule closer to clinical application and thus merits the efforts to optimize its properties. Appropriate, in-house collaborations on pharmacology and efficacy have also been set up and thus increase confidence in the ultimate success of the approach.

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