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Husband and wife team Gabsang Lee and Hyesoo Kim on the potential of stem cell research for novel therapies:
Tell me about your research.
LEE: My major focus is in using stem cells to research pain. It used to only be possible to make stem cells from embryonic cells, but new techniques allow us to create them from adult skin cells. We use these stem cells, taken from patients with pain disorders, to create pain-sensing neurons in order to understand where the patients’ symptoms are coming from and to search for new therapies. We search for specific protein markers and “signatures” from the systems we create to verify how the cells react to pain-inducing elements, such as capsaicin, a chemical derived from hot peppers. We could only use animal models before, but having the ability to create human stem cells gives us better tools to begin to understand genetic disorders, and to find drugs that cure them.
I study two diseases. CMT1A, Charcot-Marie-Tooth-1A, is one of the most common genetic diseases and has a severe impact on the quality of human life by leading to muscle and joint deterioration, as well as often causing intense pain. The other disease is CIPA, congenital insensitivity to pain with anhidrosis, which is a rare disease where the patients have absolutely no pain perception due to the lack of pain-sensing neurons. The disease is often fatal due to the potential for serious injury. So far, we still don't understand why CMT1A and CIPA patients have symptoms, and there is no effective cure for either disease. By creating CIPA- and CMT1A-specific stem cells, we can understand the diseases better and, we hope, find drugs for the patients that would be impossible to find without stem cell studies.
KIM: I focus on creating pluripotent stem cell lines—that is, cells that can grow into any kind of cell—so we can use skin cells to make stem cells from patients with interesting diseases for study.
I am director and manager of the Stem Cell Core in the Institute for Cell Engineering, a laboratory which will facilitate stem cell research within Johns Hopkins. My first tasks are to set up the laboratory and support the community by supplying cell lines to researchers. Dr. Lee’s study will use stem cells supported by the Stem Cell Core, but our research goals are slightly different. While his projects are mostly neuron development and disease modeling, the Stem Cell Core will focus on the maintenance and development of stem cell lines, genetic modification of stem cells, and creating and isolating specific cell types of stem cells. All the projects in the Stem Cell Core will be available to all of Hopkins’ labs through collaborations.
How did you become involved in stem cell research?
LEE: I went to college at the Seoul National University to get a degree as a doctor of veterinary medicine. In the last year of my training as a vet, we all went to the clinical department to try actually caring for patients—usually dogs and cats. My first patient, a brown poodle, was very sick with canine parvovirus and died despite all of my care. The medicines available at the time were unable to cure it. I felt that there should be an effort to develop methods other than just pharmacological approaches for curing diseases in animals as well as humans. Because of this experience, I switched my career from clinical work to research and began to investigate stem cells, which I believe to be the most promising way to cope with diseases with no known cures.
KIM: I was studying animal reproductive science in the graduate program at Seoul National University, which mostly involved in vitro fertilization and cloning, although I also extracted embryonic stem cells to study embryo development. Dr. Lee and I were in the same lab for our Ph.D.’s, as well as our postdoc training at the Memorial Sloan Kettering Cancer Center. I moved to studying human embryonic stem cells when we came to the U.S. because it’s one of the most fascinating areas of contemporary biology. In grad school and the lab at the Sloan Kettering Institute, we had separate projects but shared lots of materials and techniques, so we were able to help one another with the projects.
Were you excited to move to Johns Hopkins?
KIM: Of course, I was so excited to join Johns Hopkins University. As everyone knows, Hopkins is a great institute and is famous for the highest level of research. Also, with the launching of the Stem Cell Core, I get to work with many excellent stem cell scientists and to contribute to stem cell research here.
LEE: We had several choices for where we could pursue our research, but ultimately we chose Johns Hopkins because of its strong Basic Sciences research programs, and because of all the resources available for both clinical and basic research. Johns Hopkins is the top school in the U.S., as well as on this planet, for many reasons—a major one of which is its researchers. Scientific collaboration and the “neighborhood” structure of the laboratories are very important for improving research quality, and every day I benefit from the knowledge and expertise of the other researchers there.
--Interviewed by Sarah Lewin
On using a patient's stem cells to study peripheral nervous system diseases:
Video transcription: "Neural crest cells are a very transient cell population in early development. We are very interested in how neural crest cells become peripheral neurons or Swann cells or melanocytes or other cell types.
"Now, our lab has developed a new way to acquire human neural crest cells from human pluripotent stem (iPS) cells. Once we take out the patient’s fibroblasts, we add several genes that will turn those fibroblasts into pluripotent status.
"Using those stem cells, we can understand human genetic disorders and how those symptoms are presenting. And, we can also use those cells for high-throughput screening in an individualized manner and after genetic intervention, we can correct those neural crest cells and we can consider a possible transplantation back to the patient.
"One example is, there are patients who cannot feel any pain. So we think there is some sort of abnormality in pain sensory neuron development as well as the maintenance of their function. So we can make the iPS cells from those patient’s fibroblasts and we can induce those iPS cells into peripheral sensory neurons. Then we can understand why patients cannot feel any pain and from that source we may be able to find a new cure for the disease, as well as new pain killer drugs."