Mechanisms of erythroid maturation arrest in Diamond-Blackfan anemia

Diamond-Blackfan anemia (DBA) is a bone marrow failure syndrome that is characterized by impaired red blood cell production leading to severe anemia. The only available treatment options are chronic red blood cell transfusions, corticosteroids, or hematopoietic stem cell transplantation (HSCT). More effective, safer, and permanent cures for DBA are lacking, but few drugs are in active development. To develop novel therapies for DBA, a deeper mechanistic insight into physiological erythroid differentiation is essential. More than 30 mutations are known cause DBA or DBA-like syndrome through impaired ribosome function, but almost a quarter of DBA patients have no identifiable genetic cause. We have established unbiased, high-throughput systems to uncover factors that impair erythroid differentiation, and are using them to identify novel regulators of this process. Using primary patient samples and whole genome sequencing of genetically undefined DBA patients, we aim to elucidate novel DBA genes that will deepen our understanding of physiologic erythroid differentiation.

Selected Publications

Regulated GATA1 expression as a gene therapy for Diamond-Blackfan anemia
Voit RA., Liao X, Caulier A, Cohen B, Armant M, Antoszewski M, Lu HY, Fleming TJ, Kamal E, Wahlster L, Roche AM, Everett JK, Petrichenko A, Huang M, Clarke W, Myers KC, Forester C, Perez-Atayde A, Bushman FD, Pellin D, Shimamura A, William DA, Sankaran VG. (2024) Cell Stem Cell DOI: 10.1016/j.stem.2024.10.012. [DOI]

Pathogenic BCL11A variants provide insights into the mechanisms of human fetal hemoglobin silencing
Shen, Y., Li, R., Teichert, K., Montbleau, K. E., Verboon, J. M., Voit, RA., & Sankaran, V. (2021) PLoS Genetics 17(10), e1009835. [DOI]

A unified model of human hemoglobin switching through single-cell genome editing
Shen, Y., Verboon, J. M., Zhang, Y., Liu, N., Kim, Y. J., Marglous, S., Nandakumar, S. K., Voit, RA., Fiorini, C., Ejaz, A., Basak, A., Orkin, S. H., Xu, J., & Sankaran, V. (2021) Nature Communications 12(1), 4991. [DOI]