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Tim Brazelton
Assistant professor, Surgery
Developmental
Biology Program
Address
CHOP
3615 Civic Center Blvd
ARC 1116H
Philadelphia, PA 19335
Office Tel.:267-426-0201
Lab Tel.:267-426-5838
Fax: 215-590-3324
E-mail: brazelton@email.chop.edu
Link(s)
Dr.
Brazelton's Stokes page
Education
Saint Olaf College, Northfield, MN:
B.A. (Biology, Chemistry, Marine Ecology), 1991
Stanford University: Ph.D. (Plasticity of adult bone marrow cells), 2002.
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Research
Interests
- adult stem cells, plasticity, satellite cells,
skeletal muscle development, skeletal muscle regeneration, neuronal
regeneration, mesenchymal stem cells, bone marrow-derived stem cells,
muscular dystrophy, organ transplantation, chronic rejection, and
tissue remodeling.
Key
words: adult stem cells, stem cell plasticity,
muscle development, muscle regeneration, neuronal regeneration, hematopoietic
stem cells, neural stem cells, CNS regeneration, satellite cells, mesenchymal
stem cells, bone marrow-derived cells, muscular dystrophy, GFP, green fluorescent
protein, bone marrow transplantation, organ transplantation, chronic rejection,
tissue remodeling, xenotransplantation, in utero gene therapy, in utero cell
therapy
Search PubMed for articles
Description
of Research
Our initial findings that bone marrow-derived stem cells could
contribute to skeletal muscle and CNS neurons were quite unexpected.
Since these initial observations, we've learned a great deal about these
regenerative pathways. These pathways exist in both adult mice and humans,
are responsive to various types of damage, and can be regulated with proteins
or small molecules. We've demonstrated that this myogenic and neurogenic capacity
resides within single hematopoietic stem cells (SPKLS), which following
intravascular transplantation generate Purkinje neurons and skeletal muscle
(satellite) cells. Considerable experimentation has revealed that the
mechanism(s) of reprogramming (fusion versus transdifferentiation versus ?)
are unexpectedly complex and ongoing projects in my lab continue to explore
the basic biology of these cell fate transitions.
We are also continuing to study the contribution of circulating
cells to mesenchymal tissue remodeling in transplanted cardiac and lung grafts.
These transplanted organs serve not only as robust model systems for tissue
remodeling but also provide a means to better understand the etiology of chronic
rejection and dysfunction in clinically transplanted organs.
Other ongoing research involves novel strategies to treat muscle
or CNS disorders. Novel techniques for in utero delivery of cell or viral
vectors are being tested to treat murine models of muscular dystrophy and
neurodegenerative disorders. In addition, we've succeeded in getting robust
expression of exogenous proteins in the CNS of mice treated as adults.
Current work is focusing on the regulation of CNS protein expression and the
treatment of CNS disorders.
Because much of the controversy regarding stem cell fate
transitions is the result of inadequate methods to document these events,
several projects are aimed at creating improved experimental systems to track
cell fate transitions in vivo. These involve novel fluorescent proteins with
desirable characteristics, genetic reporter constructs, and the creation of
novel strains of transgenic mice.
Recent
Publications
Blau, H.M Brazelton, T.R., F.V.M. Rossi, G. Keshet, H.M. Blau.
From bone marrow to brain:Adult bone marrow-derived cells give rise to
neuronal phenotypes in mice. Science, 290:1775-9, 2000.
T.R. Brazelton, J.M. Weimann. The evolving concept of a
stem cell: Entity or function? Cell, 105:829-41, 2001.
Brazelton, T.R., M. Nystrom, H.M. Blau. Significant differences
among skeletal muscles in the incorporation of bone marrow-derived cells.
Developmental Biology, 262(1):64-74, 2003.
Corbel, S.Y., A. Lee, L. Yi, J. Duenas, T.R. Brazelton,
H.M. Blau, F.M.V. Rossi. Contribution of hematopoietic stem cells to
skeletal muscle. Nature Medicine, 9:1528-32, 2003.
Brazelton, T.R., and H.M. Blau. Optimizing techniques
for tracking transplanted stem cells in vivo. Stem Cells, 23(9):1251-65,
2005.
Lab
Rotation
Projects
- Adult stem cells:
- Identification of key regulators of pathway by which circulating
cells contribute to skeletal muscle by microarray and qPCR.
- The mechanism(s) by which bone marrow-derived cells contribute
to skeletal muscle satellite cells, myofibers, and CNS neurons.
- Isolation of the sub-population of pericytes with the capacity to
generate multiple cell fates.
- Characterization of novel genetically-based markers to track the
fate of transplanted cells in vivo.
- Gene and cell therapy:
- In utero cell therapy to treat murine models of muscular dystrophy.
- In utero lentiviral or AAV gene therapy to treat murine models of
muscular dystropy.
- In utero cell and gene therapy for robust delivery of therapeutic
proteins to the CNS.
- Organ transplantation:
- Origin of graft-remodeling mesenchymal cells following cardiac
or airway transplantation in mice.
- Lab
personnel:
- Jeremey Traas, Ph.D. Post-doctoral fellow
Anthony Tsai, M.D., Research fellow
Adam, Kaye, M.D., Research fellow
Archana Bora, Research assistant
Christina Hughes, Research assistant
*The Brazelton laboratory is one of five labs which make up the Center
for Fetal Research. In addition, to the above personnel, the CFFR maintains
it's own viral vector core, immunohistochemistry core, and imaging core.
last updated 9/2006
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