Stuart Orkin, MD, whose studies of blood cell production and hemoglobin regulation led to a gene therapy for sickle cell disease and beta-thalassemia, will deliver the next Discovery Lecture Thursday, March 27.
His presentation, “Turning Back the Hemoglobin Clock: Mechanism to Therapy and Beyond,” begins at 4 p.m. in 208 Light Hall.
Orkin is the David G. Nathan Distinguished Professor of Pediatrics at Harvard Medical School and a Howard Hughes Medical Institute investigator at Boston Children’s Hospital.
During human development, red blood cells produce a fetal form of the oxygen-carrying protein hemoglobin. Around the time of birth, fetal hemoglobin production is progressively silenced, and adult hemoglobin is expressed.
Turning fetal hemoglobin back “on” as a treatment for blood disorders caused by genetic mutations in adult hemoglobin (sickle cell disease and beta-thalassemia) was a long-sought goal, but the on-off “switch” was not understood. Orkin will review how he and his colleagues used human genetics, biochemistry and gene editing to reveal the mechanisms of the fetal hemoglobin on-off switch.
They found that the protein BCL11A is the main controller of the switch, and they demonstrated that CRISPR-based gene editing of BCL11A elicits robust fetal hemoglobin production. Their findings led to a gene therapy for sickle cell disease and beta-thalassemia; it is the first Food and Drug Administration-approved CRISPR-based gene therapy. In current work, the group aims to develop small-molecule therapeutics that mimic the gene therapy and increase fetal hemoglobin at a lower cost.
Orkin received his MD from Harvard Medical School and completed postdoctoral training at the National Institutes of Health and clinical training in pediatrics and hematology/oncology at Children’s Hospital Boston and Dana-Farber Cancer Institute.
He is a member of the National Academy of Sciences, National Academy of Medicine and American Philosophical Society. His numerous honors include the Jessie Stevenson Kovalenko Medal, George M. Kober Medal, Harrington Prize for Innovation in Medicine, and most recently, the Shaw Prize in Life Science and Medicine (2024, shared with Swee Lay Thein, DSc) and the Ernest Beutler Lecture and Prize from the American Society of Hematology (2024).
Orkin’s Discovery Lecture is sponsored by the Vanderbilt Medical Scientist Training Program.
