MAR 20, 2014 02:00 PM PDT

Cross-talk & Developmental Programs A Key to Translational Stem Cell Biology

Presented At Neuroscience
Speakers
  • Director Stem Cell Research Center & Core Facility, Professor, Sanford-Burnham Medical Research Inst, Faculty Physician, Department of Pediatrics, University of California, San Diego
    Biography
      Evan Y. Snyder earned his M.D. and Ph.D. (in neuroscience) from the University of Pennsylvania in 1980 as a member of NIH's Medical Scientist Training Program (MSTP). He had also studied psychology and linguistics at the University of Oxford. After moving to Boston in 1980, he completed residencies in pediatrics and neurology as well as a clinical fellowship in Neonatal-Perinatal Medicine at Children's Hospital-Boston, Harvard Medical School. He also served as Chief Resident in Medicine (1984-85) and Chief Resident in Neurology (1987) at Children's Hospital-Boston. In 1989, he became an attending physician in the Department of Pediatrics (Division of Newborn Medicine) and Department of Neurology at Children's Hospital-Boston, Harvard Medical School. From 1985-91, concurrent with his clinical activities, he conducted postdoctoral research as a fellow in the Department of Genetics, Harvard Medical School. In 1992, Dr. Snyder was appointed an instructor in neurology (neonatology) at Harvard Medical School and was promoted to assistant professor in 1996. He maintained lab spaces in both Children's Hospital-Boston and at Harvard Institutes of Medicine/Beth-Israel Deaconess Medical Center. In 2003, Dr. Snyder was recruited to Sanford-Burnham Medical Research Institute as Professor and Director of the Program in Stem Cell and Regenerative Biology. He then inaugurated the Stem Cell Research Center (serving as its founding director) and initiated the Southern California Stem Cell Consortium. Dr. Snyder is a Fellow of the American Academy of Pediatrics (FAAP). He also received training in Philosophy and Linguistics at Oxford University.

    Abstract:

    The therapeutic utility of stem cells is rooted in an understanding -- and exploitation -- of their natural role from earliest development to lifes end. Their job is first to participate in organogenesis and then to maintain homeostasis of that organ (e.g., the nervous system) in the face of perturbations. Accomplishment of these goals requires numerous actions, cell replacement representing but one. The tasks, in fact, require extensive cross-talk between multiple cell types (including stem cell-derived progeny themselves) and the unfolding of complex developmental programs. This complexity actually enriches the therapeutic potential of the stem cell.
    We study the behavior of neural stem cells (NSCs) in various models of injury and degeneration. During neurodegeneration and inflammation, factors are transiently elaborated which draw NSCs (even over great distances) to engage the niche and attempt restoration of equipoise by a variety of mechanisms. These actions include differentiating towards the replacement of impaired neural cells, both neurons and non-neuronal chaperone cells, all of which are essential for restitution of function. NSCs elaborate factors that promote neuroprotection, trophic support, differentiation, neuritogenesis, connectivity, angiogenesis, inhibition of inflammation and scarring. In addition to producing diffusible factors, NSCs communicate via gap junctions to re-equilibrate the intracellular metabolism of endangered neurons. NSCs may serve as vehicles for protein delivery enabling simultaneous cell and gene therapy. NSCs synergize with biomaterials to "re-engineer" damaged regions. Multimodal approaches are likely required for most neurological conditions; NSCs may serve as the glue. When studied in vitro (development- or disease-in-a-dish), NSCs may help identify novel mechanisms, drug targets, and the drugs themselves.
    While repair may entail recapitulating developmental programs, pathology (e.g., cancer) may represent the perversion of such programs. Thwarting such pathology, may involve the pharmacological re-establishment of the proper program.
    These various themes will be discussed.


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