Orkin Wins Canada Gairdner International Award | Harvard Medical School

Stuart OrkinDavid G. Nathan, a prominent professor of pediatrics at Harvard Medical School and Dana-Farber Cancer Institute, received the 2022 Canada Gairdner International Award. The award is for his research into the discovery of molecular mechanisms involved in the switching of hemoglobin gene expression from fetal to adult and for transforming this discovery into a new treatment for sickle cell disease and beta-thalassemia. It will be given.

AwardsRecognizes important biomedicine and global health research and discoveries, announced on April 5 in Toronto.

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Much of what is known about the regulation of gene expression during blood cell development can be traced directly to Orkin’s pioneering work. His latest research has led to the discovery of molecular mechanisms involved in the switch from fetal (HbF) to adult (HbA) hemoglobin gene expression during human development.

Using genetic clues from demographic studies, Orkin et al. Established that the protein BCL11A functions as an important silencer for adult HbF expression.

Recognizing that reversing HbF expression may reduce the severity of sickle cell disease and beta-thalassemia, a hereditary disease that affects HbA production, downregulation of BCL11A as a therapeutic approach Proposed.

Dialing down the amount of BCL11A reactivates HbF expression and is effectively used in place of mutant or deficient HbA in these diseases.

Orkin’s group first showed that downregulation of BCL11A expression corrects sickle cell disease in manipulated mice, a key principle demonstration of therapeutic translation.

He and colleagues have identified a site within the BCL11A gene that, when deleted by CRISPR gene editing in blood stem cells, impairs BCL11A expression in developing erythrocytes and safely reactivates HbF expression.

This study laid the foundation for promising and ongoing clinical trials in patients with sickle cell disease and beta-thalassemia, which affect more than 5 million people worldwide.

The results of these trials will have a significant impact on patients with hemoglobin disorders around the world, facilitating the future development of cheaper and easier-to-use therapies for global application.

The Gardner Foundation An annual award is given to scientists whose discoveries have had a major impact on scientific progress and human health. Since 1959, 402 scientists have been awarded the Canada Gairdner Award, and to date 96 have been awarded the Nobel Prize.

Quoted from the Gairdner Foundation news release.

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