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Laboratory of Neurophysiology
Jeffery L. Barker, M.D., Senior Investigator
Dr. Barker received his B.A. from Harvard College in 1964, and his M.D. from Boston University School of Medicine in 1968. After a surgical internship he became a PHS Commissioned Officer in 1969 to pursue a career in neuroscience at the NIH and trained primarily with Drs. Roger Nicoll (NIMH), Hal Gainer (NICHHD) and Tom Smith (NINDS). He became Chief of the NINDS Laboratory of Neurophysiology in 1981. Dr. Barker has received three PHS awards (1981, 1984, 1989) and the first Distinguished Alumnus Award from the Boston University School of Medicine (1993) given for achievement in research. Dr. Barker's lab has become focused on the physiology of CNS development and the roles of transmitters in this process using complementary strategies, including flow cytometry, imaging and electrophysiology.
Staff:
Research Interests:
The Laboratory of Neurophysiology studies the seminal biology of neural stem cells (NSCs) whose progeny subsequently compose the CNS. Immunophenotyping involving eight surface lineage and one apoptotic marker have been combined with flow cytometry to provide a comprehensive account of all lineages composing the embryonic CNS. Indicator dyes have been used in conjunction with flow cytometry to reveal cellular properties emerging in vivo as NSCs differentiate into lineage-restricted progenitors. The sort capability permits isolation of identified NSCs and progenitor populations for cellular and molecular studies in vitro.
New results include: 1) expansion of the phenotyping strategy to include all neural and non-neural lineages; 2) FACS analyses of embryonic cortical neuroepithelial cells reveals anatomical gradients in neurogenesis, apoptosis and angiogenesis; 3) isolation of nontuple-negative, vital NSCs followed by clonal analyses in medium with basic fibroblast growth factor (bFGF, FGF-2) discloses four stereotypical fates in vitro; 4) antisense knockdown of different fibroblast growth factor receptors (FGFRs) shows critical roles played by them in determining NSC fate; 5) complementary results are obtained in cortical explants treated with antisense constructs targeting different FGFRs followed by quantitative FACS analyses; 6) cellular and molecular studies of NSCs show that they express canonical transient receptor potential (TRPC) cation (Ca2+/Na+) channels; 7) TRPC1 co-localizes with FGFR-1; 8) antisense knockdown of TRPC1 attenuates both NSC proliferation and bFGF-mediated Ca2+ influx; 9) specific neurotransmitter receptor-regulated Ca2+ signaling emerges among NSC-derived progeny in a lineage-restricted manner as bFGF-mediated Ca2+ signaling becomes attenuated; 10) pharmacological activation in vitro and inhibition in vivo demonstrates developmental roles for specific neurotransmitters in different fates.
For previous publications relating to research in the Laboratory of Neurophysiology (1981-1999) see http://www.isihighlycited.com
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Selected Publications:
- Maric D, Barker JL (InPress) FACS sorting of neural stem cells and progenitors, Current Protocols in Neuroscience.
- Fiorio Pla A, Maric D, Giacobini P, Brazer SC, Liu X, Chang YH, Ambudkar IS, Barker JL (2005) TRPC1 plays a role in bFGF/FGFR-1-induced Ca2+ entry and rat neural stem cell proliferation, J. Neuroscience 25, 2687-2701.
- Maric D, Barker JL (2004) Neural stem cells redefined: a FACS perspective, Molecular Neurobiology 30, 49-76.
- Ma W, Fitzgerald W, Liu QY, O'Shaughnessy TJ, Maric D, Lin HJ, Alkon DL, Barker JL (2004) CNS stem and progenitor cell differentiation into functional neuronal circuits in three-dimensional collagen gels, Experimental Neurology 190, 276-288.
- Maric D, Maric I, Chang YH and Barker JL (2003) Prospective cell sorting of neural stem cells and neuronal and glial progenitors reveals selective effects of bFGF and EGF on self-renewal and lineage progression., J Neuroscience 23, 240-251. Full Text/Abstract
All Selected Publications
Contact Information:
Dr. Jeffery L. Barker
Laboratory of Neurophysiology, NINDS
Building 49, Room 2A20
MSC4479
Bethesda, MD 20892-4123
Telephone: 301-496-2414 office,
301-496-2414 laboratory,
301-402-1565 fax
Email: barkerj@ninds.nih.gov
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