Awardee Profile - George Daley

George Q. Daley, M.D., Ph.D.

2006 - Dr. George Q. Daley believes that when it comes to utilizing stem cells for research, 20 years from now people will look at our current time as a historical curiosity.

“There’s always a certain amount of hesitation when new technologies are introduced,” Dr. Daley said. “Especially when that technology challenges the way we look at ourselves.”

He cites organ transplants and in vitro fertilization, which at one time were controversial, but now are a part of the fabric of medical research and clinical care.

“There is a lot of controversy around stem cells, but as people learn about the profound medical applications of stem cells are and realize we are not cloning people, an increasing percentage of the population is accepting this work,” he said. “More and more people have endorsed stem cells as an important avenue of biomedical research.”

Dr. Daley is the associate director of the Stem Cell Program at Children’s Hospital in Boston and serves on the executive committee of the Harvard Stem Cell Institute. He received a 2003 Clinical Scientist Award in Translational Research and a 1996 Career Award in Biomedical Science from the Burroughs Wellcome Fund. He is heavily involved in public policy regarding stem cell research and is the president-elect of the International Society for Stem Cell Research.

His involvement with stem cell research emanated from his research on blood stem cells in leukemia, primarily human chronic myeloid leukemia (CML). He was interested in how the cells develop related to the disease—pathologically—compared to how they develop normally.

CML is caused by an activated mutant version of the human ABL gene called BCR/ABL. As a graduate student at the Massachusetts Institute of Technology, Dr. Daley proved BCR/ABL caused the leukemia by genetically modifying mice to express the gene. The mice eventually developed leukemia.

Inspired in part by this validation, Dr. Brian Drucker, also a BWF awardee, helped the pharmaceutical company Novartis, created Imatinib (Gleevec TM), a drug that blocks the action of BCR/ABL and sends the cancer into remission in 98 percent of the patients. However, if the patients have had the disease for a few years or if the disease is at an advanced stage when treatment is started, the drug is less effective. Patients become resistant to the drug when mutations occur in the BCR/ABL gene—the same way some bacteria develop antibiotic resistance.

Dr. Daley has been able to create mutations in BCR/ABL in vitro, and to identify which mutations cause drug-resistance. This approach has allowed him to anticipate many of the random mutations one might encounter in a patient, and to design drug treatment strategies to defeat CML.

By testing new combinations of drugs—including a class of drugs, called Farnesyl protein transferase inhibitors (FTIs), poised to become approved for leukemia treatment—Daley’s team has shown that the drugs work effectively in concert with Gleevec TM, but when used over time in leukemia patients, still may encounter resistance.

“We can monitor patients and follow their progression during a period of time,” he said. “If we detect a mutation that new drugs resist, we can tailor therapy specifically for the patient.”

The problem with most leukemias is that the exact problem allowing uncontrolled growth is generally unknown. General chemotherapy and/or a bone marrow transplant traditionally have been the only treatment options available, but these are heavy handed approaches. Bone marrow transplants have serious limitations related to the difficulty of finding perfect matches for patients. A close but imperfect match is considered suboptimal and can lead to a complication called graft-versus-host disease, in which the transplanted bone marrow attacks the patient's organs.

In other experiments, Dr. Daley is attempting to develop a way to create perfectly matched stem cells for a given patient by reprogramming their skin cells and differentiating them into hematopoietic stem cells--the "seeds" of a body's blood. These customized stem cells would then be transplanted back into the body after cancer cells have been eliminated by radiation, in hopes of curing the patient with a new complement of healthy blood.
 

By Russ Campbell, BWF communications officer.