Kevin Bunting, Ph.D. studies a single molecule in the hopes of solving a multitude of childhood diseases.
Bunting, a researcher at the Aflac Cancer Center and Blood Disorders Service of Children’s Healthcare of Atlanta and an Associate Professor of Pediatrics at Emory University, is a master of patience, realizing that his discoveries might take as long as a decade to see in clinical practice.
That said, Bunting’s study of the molecule, STAT5, is showing great promise—perhaps allowing grafts of healthy cells to replace existing tissue without the harshness of radiation. And that could dramatically affect the cure rates of several diseases, from hemophilia to sickle cell to leukemia.
STAT5, known as a “transcription factor” regulates dozens of molecules. These molecules determine how well stem cells reside in bone marrow and how rapidly they duplicate themselves, and by eliminating STAT5, it might be possible to replace sick stem cells with healthy ones or to kill leukemic stem cells “I study how you get existing stem cells to leave and die and allow the new ones to take their place—basically it’s musical chairs,” he said.
Right now, “radiation wipes out everything,” he said. But if STAT5 molecules can be reduced or eliminated in bone marrow, it would allow a physician to essentially prune out bad stem cells like a gardener, instead of bulldozing through all the other supporting cells like a landscaper.
And that ability would be a revolutionary change in treatment options, providing physicians a less-toxic solution that does not damage the DNA. The application could also be stretched beyond treating cancer and blood disorders and could be extremely effective in solid organ transplants, again making rejection a far smaller risk.
So how does the ideal become reality? Through a series of small incremental steps—and the help of hundreds of mice, he said.
First, there was the ah-hah moment: Bunting, with colleagues, discovered that STAT5-deficient cells still could maintain blood counts and survival, but didn’t have the ability to keep reproducing “bad” cells after transplantation. Then there was awareness: this discovery had widespread potential to actually cure hematology and oncology ailments.
And finally, there was—and is—the work: scouring through readily available drugs to see what off-label effects might achieve the STAT5-deficient effect; keeping in touch with the two or three other labs in the nation studying the role of STAT5 in blood stem cells, and conducting painstakingly precise research—done with a few humans, and again, those hundreds of mice.
Most of the journey has been at the Department of Medicine’s Division of Hematology/Oncology at Case Western University. However, Bunting moved his operation to the Aflac Cancer Center.
“There’s several benefits to being here,” Bunting said. “But one of the best is that the Aflac Cancer Center offers a full-spectrum program—from basic science to the clinical applications. It’s a great opportunity.”
Also, the Aflac Cancer Center treats such a “volume of patients,” it provides the perfect environment for robust basic research, he said. The center treats more than 350 new cancer patients each year and follows more than 2,500 patients with sickle cell disease, hemophilia and other blood disorders.
Bunting says he is busy “establishing connections with Children's physicians.” Todd Cooper, D.O., Director of the Aflac Cancer Center's Leukemia/Lymphoma Innovative Therapy Program, is his main contact for new drug treatment strategies, and for the transplantation area, he’s working with both the Hemophilia and Gene Therapy Programs.
And, he hopes within a year to be able to present proof that he—armed with his knowledge of STAT5 function—can cure a mouse with leukemia or hemophila, by taking advantage of the critical role of STAT5 in blood stem cells.
But it will take more patience in the lab.
“Science is a long-term process with the end result often taking years if it works out well,” Bunting said.