HHMI Investigator Stuart Orkin honored for research that paved the way for new treatments for sickle cell disease and debilitating blood disorders affecting millions of people worldwide.
Investigator, Boston Children's Hospital

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HHMI Investigator Stuart Orkin honored for research that paved the way for new treatments for sickle cell disease and debilitating blood disorders affecting millions of people worldwide.
KEY TAKEAWAYS
  • HHMI Investigator Stuart Orkin received the 2026 Breakthrough Prize in Life Sciences for pioneering research on hemoglobin regulation that led to revolutionary new treatments for blood disorders. He shares the prize with Swee Lay Thein of the National Institutes of Health.
  • Sickle cell disease and beta-thalassemia are caused by mutations in the adult form of hemoglobin. Orkin’s lab discovered that the gene BCL11A acts as the master switch that shuts off fetal hemoglobin production after birth — and that silencing BCL11A can reactivate production of healthy fetal hemoglobin, offering a path to treating sickle cell disease and beta-thalassemia. 
  • This research directly enabled development of the first FDA-approved therapy using CRISPR gene editing, which is now used to treat both diseases. 

HHMI Investigator Stuart Orkin was awarded the 2026 Breakthrough Prize in Life Sciencesexternal link, opens in a new tab for research on hemoglobin that led to transformational new treatments for sickle cell disease and beta-thalassemia, blood disorders that together affect millions worldwide. He shares the prize with Swee Lay Thein of the National Heart, Lung, and Blood Institute of the National Institutes of Health. 

“Stu Orkin’s career-spanning journey to uncover the biological mechanisms behind devastating blood disorders is a testament to the long-term impact of curiosity-driven science,” said HHMI President Erin O’Shea. “His research has opened the door for new treatments for sickle cell disease, profoundly transforming the lives of people around the globe. All of us at HHMI congratulate him on this well-deserved recognition.”  

Finding the Hemoglobin Switch 

Hemoglobin is the protein in red blood cells that carries oxygen. Shortly after birth, the body stops making fetal hemoglobin and switches to an adult form. Sickle cell disease and beta-thalassemia are both caused by genetic mutations in adult hemoglobin, leading to abnormal blood cells and reduced oxygen that can cause anemia, fatigue, pain, increased risk of infection, and potential organ damage. Since fetal hemoglobin does not have genetic mutations in these patients, scientists had long sought to find a way to turn it back on as a way to restore normal hemoglobin to the body.  

In 2007, Thein and her collaborators were the first to identify a link between the gene BCL11A and fetal hemoglobin. Independently, Orkin identified the same gene with collaborators in Sardinia.  

Orkin and his team at Boston Children’s Hospitalexternal link, opens in a new tab then went on to show that BCL11A controls the switch from fetal to adult hemoglobin. By modeling sickle cell disease in mice, they found that reducing the expression of BCL11A reactivates the production of fetal hemoglobin and cures the disease.  

CRISPR-based Treatments for Sickle Cell Disease

Orkin and his colleagues subsequently identified an enhancer region within the BCL11A gene that specifically controls production of the protein in red blood cells. They then showed that CRISPR gene editing could be used to edit a precise site within this enhancer to reduce BCL11A expression in red blood cells and reactivate fetal hemoglobin production.  

The research laid the groundwork for the development of Casgevy, a treatment for patients with sickle cell disease and beta-thalassemia that is also the first FDA-approved therapy using CRISPR/Cas9 genome editing. 

“When I began my career, the notion of using gene modification to treat a disease was fantasy,” said Orkin. 

Casgevy provides a functional cure for patients, but it is expensive and takes months of hospitalization to complete treatment. Orkin and his team are now working to better understand the structure of the BCL11A protein with a goal of developing small molecule therapeutics – inexpensive pills that are just as effective in treating hemoglobin disorders.  

“I hope that this recognition will bring more attention and investment in research that will ultimately lead to clinical benefit for all patients with hemoglobin disorders, wherever they live. Then, the true promise of molecular therapy will be realized,” Orkin said. 

Orkin has been an HHMI Investigator for more than 40 years and trained generations of scientists, including other HHMI Investigators who have gone on to lead their own research programs. 

“Stu Orkin’s groundbreaking discoveries into hemoglobin regulation over many decades represent just one piece of his extraordinary scientific impact,” said HHMI Chief Scientific Officer Leslie Vosshall. “His dedicated mentorship of future generations of scientists ensures that pioneering research in this field will continue for decades to come.” 

“I am thrilled that the Breakthrough Foundation chose to recognize our work, which is the product of dedicated and brilliant trainees I have been fortunate to mentor,” Orkin said. 

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About HHMI  
The Howard Hughes Medical Institute (HHMI) is a private scientific research institution advancing the discovery and sharing of scientific knowledge for the benefit of humanity. For more than 70 years, HHMI has invested in scientists who make discoveries that further human health and our fundamental understanding of biology. HHMI also supports innovative approaches to science education and public engagement to energize and support future generations of scientists and foster public appreciation for science.  

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