Tisdale's Working Group
John Fitzgerald Tisdale, M.D.
Dr. Tisdale’s working group is researching multiple strategies in the laboratory and the clinic to cure sickle cell disease (SCD) by repairing or replacing the precursor bone marrow cells that give rise to sickled red blood cells. Bone marrow transplants from healthy donors are used successfully to treat certain blood cancers for which the course of the disease is so severe that the destruction of the patient’s own immune system through high-dose chemotherapy and radiation seems an effective compromise. However, the therapeutic balance in the case of SCD is less clear; children tolerate transplants more successfully, but they are also less imminently threatened by the disease. The success of conventional transplants in adults, whose need is more immediate, is less clear.
The issue of immune tolerance is, of course, central to transplantation research. Dr. Tisdale has an active research program in trying to characterize tolerance and create conditions in which patients will more easily tolerate donor cells and tissues without the need for destroying the immune system or perpetual use of immunosuppressant drugs. The program is also working on gene addition strategies that will harness the machinery of viruses to act as delivery vectors to provide a correct copy of the normal or a therapeutic gene to the patient's own bone marrow cells. Finally, his group is working to develop the means to correct the genetic mutation by gene editing strategies among pluripotent stem cells.