Profiles in Pluripotence: Systems Biology of Stem Cells
Posted May 18, 2009
A central biological research challenge is clarifying how cells that share the same DNA differentiate to form the various tissues in the body, and how this process goes amiss in diseases such as cancer. These issues are critical to both therapeutic and research use of stem cells.
On March 17, 2009, three stem cell researchers shared their explorations of the biochemical interactions that reinforce developmental pluripotence or differentiation, and how systems biology techniques help illuminate these interactions. Jeanne Loring and her colleagues are looking for a signature of pluripotence, using several high-throughput techniques to collect data on expression of both protein-coding and microRNAs, epigenetic modifications of DNA, and genome structure. Raju Chaganti and his colleagues are studying a type of pluripotent cell line that comes from embryonal carcinomas. Ihor Lemischka and his group are using mouse embryonic stem cells to probe the molecular events underlying differentiation, and how signaling events influence them.
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Books and Web Sites
Loring J. ed. 2007. Human Stem Cell Manual: A Laboratory Guide, Elsevier, New York, New York.
Loring's lab set up this wiki to share data and discuss results on their stem cell research.
Bibikova M, Chudin E, Wu B, et al. 2006. Human embryonic stem cells have a unique epigenetic signature. Genome Res. 16: 1075-1083. Full Text
Laurent LC, Chen J, Ulitsky I, et al. 2008. Comprehensive microRNA profiling reveals a unique human embryonic stem cell signature dominated by a single seed sequence. Stem Cells 26: 1506-1516. Full Text
Müller FJ, Laurent LC, Kostka D, et al. 2008. Regulatory networks define phenotypic classes of human stem cell lines. Nature 455: 401-405. Full Text
Chadalavada RS, Korkola JE, Houldsworth J, et al. 2007. Constitutive gene expression predisposes morphogen-mediated cell fate responses of NT2/D1 and 27X-1 human embryonal carcinoma cells. Stem Cells 25: 771-778. Full Text
Houldsworth J, Korkola JE, Bosl GJ, Chaganti RS. 2006. Biology and genetics of adult male germ cell tumors. J. Clin. Oncol. 24: 5512-5518.
Ivanova N, Dobrin R, Lu R, et al. 2006. Dissecting self-renewal in stem cells with RNA interference. Nature 442: 533-538.
Schaniel C, Li F, Schafer XL, et al. 2006. Delivery of short hairpin RNAs—triggers of gene silencing—into mouse embryonic stem cells. Nat. Methods 3: 397-400.
Whetton AD, Williamson AJ, Krijgsveld J, et al. 2008. The time is right: proteome biology of stem cells. Cell Stem Cell 2: 215-217.
Jeanne Loring, PhD
Jeanne Loring is professor of developmental neurobiology and founding director of the newly created Center for Regenerative Medicine at the Scripps Research Institute. Loring has held research and management positions at biotechnology companies including Hana Biologics, GenPharm International, Molecular Dynamics, and Incyte Genomics, and was most recently the co-director of one of the country's first NIH-funded stem cell centers, at the Burnham Institute for Medical Research.
Loring was chair of the Clinical Neuroscience review committee of the National Institutes of Health (NIH), was recently cochair of the NIH Neuroscience Blue Print and NIH Regenerative Medicine Roadmap Workshops, and currently serves as cochair for the Regulatory and Ethics Board for the Bill and Melinda Gates Foundation Global Challenge 4. She is a member of the Society for Neuroscience, Society for Developmental Biology, ASCB, ISSCR, American Society for Gene Therapy, and ISCI (International Stem Cell Initiative), a multinational group that is establishing scientific standards for human embryonic stem cell research.
Loring has been working with human embryonic stem cells for nearly a decade, and her current research focuses on discovering the molecular basis of their pluripotence and differentiation. A key goal of her research is to discover the key elements that control the unique human embryonic stem cell regulatory molecular network and use this knowledge for improved reprogramming methods for human somatic cells.
In addition to investigating the fundamental biology of human embryonic stem cells, Loring is developing practical applications for these cells for drug discovery, drug delivery, and cell therapy. A major interest of her laboratory is to use stem cells to discover novel therapies for Alzheimer's disease.
Loring is also training the next generation of stem cell scientists. She is director of Human Embryonic Stem Cell Training Courses for the NIH and CIRM (California Institute for Regenerative Medicine) and author of a popular laboratory manual for human stem cell research.
Raju Chaganti, PhD
Raju Chaganti received a PhD degree in biology and genetics from Harvard University. Following postdoctoral training in mammalian genetics at the Medical Research Council of Great Britain, and a brief stint as a lecturer in botany at the Andhra University, India, he returned to the United States to take up a research position in human genetics at the New York Blood Center and Cornell University Medical Center in New York City. In 1975, he was invited to join the faculty of Memorial Sloan-Kettering Cancer Center in New York City to develop a program of research in cancer genetics and develop a genetic diagnostic laboratory dedicated to cancer, the latter the first if its kind in the country.
Chaganti continues on the faculty of Memorial Sloan-Kettering Cancer Center as a member and incumbent of the William E. Snee Chair in the Department of Medicine and the Cell Biology Program. He is a professor of cell biology in the Gerstner Graduate School of Biomedical Sciences of the Sloan-Kettering Institute for Cancer Research and a professor of cell biology and genetics in the Weill-Cornell Graduate School of Medical Sciences. Chaganti authored, along with numerous colleagues in his group, over 350 publications reporting studies of plant, animal, and human genetics.
Ihor Lemischka, PhD
Ihor Lemischka is director of the Black Family Stem Cell Institute and professor of gene and cell medicine at Mount Sinai School of Medicine. An internationally renowned stem cell biologist, Lemischka has patented techniques to isolate stem cells and has significantly advanced the study of stem cell activity and behavior.
Stem cell research has clinical implications for many diseases. The first step is to understand what makes the stem cell "decide" what type of cell it will become and how it communicates with neighboring cells. Lemischka hopes to characterize the stem cell's decision-making process and regulatory network, which will then help scientists manipulate stem cell decisions and develop therapies that could treat diseases.
A vocal advocate of stem cell research, Lemischka believes the latest findings about stem cells are just the tip of the iceberg of all the medical advances that will come from stem cell research. Lemischka stands by the notion that scientific freedom is key to resolving some of the biggest mysteries in medicine.
A member of the International Society for Stem Cell Research, he has traveled the world to educate the public about stem cell behavior and has delivered countless lectures about stem cell differentiation.
Lemischka earned his PhD at Massachusetts Institute of Technology. There, he served as a postdoctoral research associate and also completed a fellowship at MIT's Center for Cancer Research. Lemischka then went to the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts where he completed another postdoctoral fellowship. In 1986, he joined the faculty at Princeton University where he rose from assistant professor to professor of molecular biology. He remained on the Princeton faculty for 21 years before moving to Mount Sinai.
Don Monroe is a science writer based in Murray Hill, New Jersey. After getting a PhD in physics from MIT, he spent more than fifteen years doing research in physics and electronics technology at Bell Labs. He writes on physics, technology, and biology.