George Daley, M.D., Ph.D.
George Daley, M.D., Ph.D.
Samuel E. Lux, IV Chair in Hematology; Director, Stem Cell Transplantation Program, Childrens Hospital Boston, Boston, Massachusetts
Comparative Phenotypic, Functional, and Molecular Analysis for ESC and iPSC
Administered by the NHLBI Division of Blood Diseases and Resources, Transfusion Medicine and Cellular Therapeutics Branch
FY 2009 Recovery Act Funding: $1,748,199
George Q. Daley, M.D., Ph. D., is a pioneer in stem cell biology - a field he describes as a "magnet" for physician-scientists like himself who see patients and also work in the lab. Dr. Daley is on a quest to unravel the mysteries of how cells "decide" to become any of the more than 200 different cell types in the human body. Within the next few years, he predicts, stem cells will offer a precise tool for screening new medicines as well as an accurate model for studying a range of human diseases.
Research Focus: There are two basic types of human stem cells: embryonic stem (ES) cells and non-embryonic, or "adult" stem cells. ES cells have a truly "clean slate," and as such can become any cell type. Adult stem cells, on the other hand, are already partially and irreversibly specialized toward a particular cell type.
In 2007, researchers came up with a third type by inventing a breakthrough technique that transforms, or re-programs, cells that have already "grown up" back to those that look and act like cells from an embryo. Making these induced pluripotent stem, or iPS, cells involves supplementing ordinary skin cells with four specific molecules that somehow "turn back the clock," restoring the cells to their original, clean-slate state.
Dr. Daley's lab was the first to generate multiple, patient-specific iPS cells from the skin of people who have a genetic disease. He has used these cells to study what are mostly rare diseases in a way that has not been possible before.
Grant Close-Up: Dr. Daley and other researchers are now discovering that iPS cells and ES cells aren't exactly the same. With support from the Recovery Act, Dr. Daley and his team aim to map out the differences between the two types of cells, an essential task if the cells will ever be used as therapies in people.
Recent experiments hint that the re-programming process leaves an imprint on iPS cell DNA, a chemical change called methylation, which is different from that on ES cells. Are those markings reversible? Do they affect the cell's function? Can scientists alter the re-programming process to eliminate these differences? These are questions Dr. Daley will answer with his Recovery Act grant by thoroughly comparing the molecular properties of ES and iPS cells.
"The whole field of stem cell biology is asking these questions," Dr. Daley said, "and I'm confident we can get the answers in two years."
Economic Impact: Recovery Act funding came at an "unbelievably good time," said Dr. Daley, noting that the flagging economy had forced him to reduce his lab staff. Since September 2009 when he received the new NIH funding, he has hired several new employees.
In particular, Dr. Daley thrives on the energy, enthusiasm and creativity inspired by junior scientists in his lab. He considers himself lucky to have several young physician-scientists who share his excitement about the ability of stem cell research to revolutionize medicine.
One trainee is creating iPS cells from a patient with a genetic disease that leads to severe bone marrow failure. Another is tracing the steps in which ES cells mature into blood cells. Still another is studying the role of adult stem cells in leukemia.
Tomorrow's Scientists: As hematologists who treat disorders of the blood, Dr. Daley and other physicians at Children's Hospital Boston sometimes treat kids and teens with sickle cell disease. In this inherited condition, red blood cells become deformed and cannot carry oxygen like they should. Left untreated, the disease can be very painful and can cause severe organ damage or death. Researchers continue to study the origin and progression of this disease, hoping to learn how to prevent it.
Last summer, one such patient approached Dr. Daley about doing research in his lab.
"He's a very engaging, thoughtful guy," said Dr. Daley, of his 16-year old protègè who also plays the cello. The student participated in a Recovery Act-funded project in which he helped create iPS cells from mice. The hope is that these cells would serve as a useful tool to better understand how to treat various blood diseases.
Dr. Daley said he hopes to hire the student again this coming summer and ultimately, to help him to discover his own passion for research.
"I think I have the best job on earth!" Dr. Daley said.
By Alison Davis, Ph.D.