Among the notable alumni of the Orkin lab is Vijay Sankaran, MD ’09, PhD ’10, the Jan Ellen Paradise, MD Professor of Pediatrics at Harvard Medical School—and first author of the Orkin lab’s landmark 2008 paper on the BCL11A gene, which he wrote as an MD-PhD student in the Orkin lab. Today, he is principal investigator in a groundbreaking lab of his own. The Sankaran lab’s research, with Hanna Gazda, MD, PhD, into ribosomal mutations promises therapies to treat Diamond-Blackfan anemia (DBA)—a rare, life-threatening disorder in which bone marrow cannot make mature, functioning red blood cells—and has led to a universal gene therapy that is about to enter clinical trials.

Mentored by Drs. Orkin and Altshuler during his own training, Dr. Sankaran now mentors a new generation of physician–scientists in his lab, including alumna Jessica Lacy Yasuda, MD ’14, now a gastroentereologist at Boston Children’s Hospital. Sankaran also advises HMS students through the Scholars in Medicine program.

How a genetic insight paired with gene editing technology led to a life-changing new therapy

Stuart H. Orkin, MD ’72, David G. Nathan Distinguished Professor of Pediatrics at HMS and HHMI Investigator at Boston Children’s Hospital, and his lab led the research that made CASGEVY—the world’s first FDA-approved CRISPR gene therapy for sickle cell disease—possible. They showed that sickle cell disease disrupts adult hemoglobin but leaves fetal hemoglobin, which the body normally stops producing when it begins producing adult hemoglobin, unaffected. Working with then MD-PhD student Vijay Sankaran, NIH patient samples, and collaborators in Italy, Orkin identified BCL11A, the gene that controls the body’s switch from fetal to adult hemoglobin production. The team’s 2008 paper in Science opened new directions in sickle cell research. Five years later, Orkin lab member Daniel Bauer, MD, PhD, found a key DNA sequence in BCL11A that controls its activity. From there, another of Sankaran’s professors, David Altshuler, MD ’94, PhD ’94, and his team at Vertex Pharmaceuticals transformed these discoveries into CASGEVY, marking a new era in gene therapy.