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Rene E. Harrison
Ph.D. (University of
Toronto)
Associate Professor in Zoology
Phone: 416-287-7377
Fax: 416-287-7676
e-mail: harrison@utsc.utoronto.ca
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My research interests are in the area of cell polarity. Reorganization
of cytoplasm and creation of unique plasma membrane domains is a shared phenomenon
amongst various cell types to carry out their specialized functions. Such dramatic
cell shape changes are orchestrated by the cytoskeleton, principally microtubules
which extend throughout the cytosol. This proteinaceous network serves as a
conduit for the delivery of key signaling proteins and membrane elements required
for the consequent cell surface morphological changes.
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Current Research Projects
I
am currently studying the cytoskeleton in cell polarization in several
cell
types: macrophages, osteoclasts and
neurons. Macrophages are crucial
front-line cells in the body’s defense against infection. Macrophages
destroy pathogens by phagocytosis, a process whereby pathogens are
engulfed by extensive plasma membrane extensions, called pseudopods.
Pseudopods develop
at the site of plasma membrane attachment to the pathogen and polarized
fusion of intracellular membrane stores at this site allow the pseudopods
to surround
and internalize the target pathogen.
Osteoclasts are bone cells function to focally target acidic organelles
to the bone apposed plasma membrane region. Fusion of these acidic organelles
with the basal plasma membrane creates a highly asymmetric cell surface,
termed the ruffled border, which serves as the bone-resorbing organelle.
While osteoclasts are crucial for calcium store release and normal bone remodeling,
these cells are also the highly destructive instigators of bone degeneration
in diseases including osteoporosis, rheumatoid arthritis, multiple myeloma
and metastatic cancers.
Neurons are one of the most polarized cell types in the body: with
cell processes extending up to metres away from the cell body. Neuronal function
depends on trafficking of secretory vesicles containing neurotransmitters
to the ends of the extensive cell processes. Understanding the molecular
regulation of secretory vesicle trafficking is key to understanding neuronal
disorders where neurotransmitter release is impaired.
Microtubules are implicated in the trafficking of organelles to the
active plasma membrane region of all of these cells. We are studying microtubule-associated
proteins, microtubule motors and signaling elements responsible for this
translocation.
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Research Opportunities
I am taking CV’s
from interested graduate students and postdoctoral fellows.
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Research Group
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Arian Khandani, M.Sc.
Edward Eng
David Douda
Salma Rawof
Payman Tehrani
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Research Assistant
Ph.D. Student
M.Sc. student
4th Year Project Student
4th Year Project Student |
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Recent Publications
- Nabavi N., Urukova Y., Cardelli M., Aubin J.E. & Harrison R.E. (2008) Lysosome dispersion in osteoblasts accommodates enhanced collagen production during differentiation. J Biol Chem, 283, 19678.
- Patel P.C. & Harrison R.E. (2008) Membrane ruffles capture C3bi-opsonized particles in activated macrophages. Mol Biol Cell, 19, 4628.
- Binker M.G., Zhao D.Y., Pang S.J. & Harrison R.E. (2007) Cytoplasmic linker protein-170 enhances spreading and phagocytosis in activated macrophages by stabilizing microtubules. J Immunol, 179, 3780.
- Eng E.W., Bettio A., Ibrahim J. & Harrison R.E. (2007) MTOC reorientation occurs during FcgammaR-mediated phagocytosis in macrophages. Mol Biol Cell, 18, 2389.
- Khandani A., Eng E., Jongstra-Bilen J., Schreiber A.D., Douda D., Samavarchi-Tehrani P. & Harrison R.E. (2007) Microtubules regulate PI-3K activity and recruitment to the phagocytic cup during Fcgamma receptor-mediated phagocytosis in nonelicited macrophages. J Leukoc Biol, 82, 417.
- Touret N., Paroutis P., Terebiznik M., Harrison R.E., Trombetta S., Pypaert M., Chow A., Jiang A., Shaw J., Yip C., Moore H.P., van der Wel N., Houben D., Peters P.J., de Chastellier C., Mellman I. & Grinstein S. (2005) Quantitative and dynamic assessment of the contribution of the ER to phagosome formation. Cell, 123, 157.
- Harrison R.E., Brumell J.H., Khandani A., Bucci C., Scott C.C., Jiang X., Finlay B.B. & Grinstein S. (2004) Salmonella impairs RILP recruitment to Rab7 during maturation of invasion vacuoles. Mol Biol Cell, 15, 3146.
- Vieira O.V., Harrison R.E., Scott C.C., Stenmark H., Alexander D., Liu J., Gruenberg J., Schreiber A.D. & Grinstein S. (2004) Acquisition of Hrs, an essential component of phagosomal maturation, is impaired by mycobacteria. Mol Cell Biol, 24, 4593.
- Harrison R.E., Bucci C., Vieira O.V., Schroer T.A. & Grinstein S. (2003) Phagosomes fuse with late endosomes and/or lysosomes by extension of membrane protrusions along microtubules: role of Rab7 and RILP. Mol Cell Biol, 23, 6494.
- Jongstra-Bilen J., Harrison R. & Grinstein S. (2003) Fcgamma-receptors induce Mac-1 (CD11b/CD18) mobilization and accumulation in the phagocytic cup for optimal phagocytosis. J Biol Chem, 278, 45720.
- Harrison R.E., Touret N. & Grinstein S. (2002) Microbial killing: oxidants, proteases and ions. Curr Biol, 12, R357.
- Harrison R.E. & Grinstein S. (2002) Phagocytosis and the microtubule cytoskeleton. Biochem Cell Biol, 80, 509.
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Teaching
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