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Principal Investigator:
Schwob, James, M.D., Ph.D.
George A. Bates Professor of Histology and Chair Department of Anatomy
and Cellular Biology
Department
of Anatomy & Cellular Biology
Tufts University
School of Medicine
136 Harrison Avenue
Boston, Massachusetts 02111
Office Phone:
(617)636-6626
Lab Phone:
(617)636-2418
FAX:
(617)636-0823
EMail
Address:
jim.schwob@tufts.edu
Program
in Cellular and Molecular Biology
Sackler School
Medical
School
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Neurogenesis:
| Progenitor
cells in the olfactory epithelium of normal animals are fated to make
neurons. In contrast, following forms of injury that destroy both
neurons and non-neuronal cells, progenitor
cells become multipotent and capable of reconstituting all of
the cell types found in the epithelium. We are using cell sorting
techniques based on antibodies to cell surface antigens that we developed
to identify, isolate, culture and transplant
epithelial stem cells (see below). Remarkably, the stem cells
engraft, proliferate, make neurons and non-neuronal cells. Even more
remarkably, the neurons generated by the transplanted stem cells send
axons that innervate the appropriate part of the olfactory bulb. A
further strategy used to attack the problem of progenitor cell regulation
is the use of cell lines to define the growth
factors that participate in that regulation and the mechanisms responsible
for their transduction (see below). Finally, we are using retroviral
vectors to deliver dominant-negative and constitutively-active components
of cell signalling pathways to assess their participation in the regulation
of progenitor cell behavior. Among these are the Notch signalling
system, its downstream effectors including Hes1 (for Hairy-Enhancer
of Split homologue 1), and their targets among the family of bHLH
transcription factors that direct neuronal differentiation. These
experiments will let us define how olfactory neurogenesis is regulated
at a molecular level, and whether olfactory stem cell-derived neurons
will help the brain recover after injury.
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| Program
in Cell, Molecular, and Developmental Biology
136 Harrison Avenue, 5th Floor
Boston, MA 02111 617-636-6685
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