This week, we profile a recent publication in Cell Stem Cell by Dr. Vijay Sankaran from Boston Children’s Hospital, Dana-Farber Cancer Institute, and Harvard Medical School. The Sankaran Lab (pictured) studies how human genetic variation impacts blood cell production or hematopoiesis in health and disease. Learn about their findings in our Q&A.
Can you provide a brief overview of your lab’s current research focus?
We are broadly interested in how human genetic variation can impact the process of blood and immune cell production, or hematopoiesis, in health and disease. Related to this, we seek to develop improved methods for studying hematopoiesis.
What is the significance of the findings in this publication?
We have shown that over 30 distinct mutations that cause Diamond-Blackfan anemia, a rare blood disorder due to impairments in ribosome production, converge on impaired translation of the erythroid master transcription factor GATA1 to cause this disease. Increasing GATA1 expression can rescue the impaired red blood cell production in Diamond-Blackfan anemia. However, GATA1 can also cause blood stem cells to differentiate. So we needed to design an approach to allow GATA1 to be expressed appropriately to enable therapy for all patients with Diamond-Blackfan anemia. In this paper, we describe the approach we took to design a gene therapy that can achieve regulated GATA1 expression, while also enabling the vector to integrate into blood stem cells.
What are the next steps for this research?
Based on these results and some additional safety data we have now obtained, we seek to file an FDA Investigational New Drug application soon, which would allow us to initiate a clinical trial at Boston Children’s Hospital of this gene therapy approach for Diamond-Blackfan anemia.
This work was supported by the Blavatnik Therapeutics Challenge Award from Harvard Medical School, Boston Children’s Hospital, the NIDDK, the NHLBI, and the Howard Hughes Medical Institute.
