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Faculty
Joel Pachter
Professor of Cell Biology
pachter@nso1.uchc.edu
Areas of Interest:
The major focus in this laboratory is to elucidate the mechanisms by
which leukocytes and pathogens invade the central nervous system (CNS).
Movement of both soluble and cellular elements into the CNS is regulated
by microvessel endothelial cells comprising the blood-brain barrier
(BBB). It is thus believed that alterations in the BBB contribute to the
pathogenesis of various neuroinflammatory, neuroinfectious and
neurodegenerative diseases such as multiple sclerosis, AIDS dementia
complex and Alzheimer disease. To evaluate the role played by the BBB in
these disorders, we are employing an in vitro culture model of the human
BBB recently developed in this laboratory. Studies in progress in this
laboratory include the following: 1) regulation of leukocyte migration
across the BBB; 2) viral interactions with the BBB; 3) estrogen effects
on the BBB; 4) cannabinoid regulation of CNS inflammation; and 5.)
genomic and proteomic analysis of brain microvascular endothelial cell
heterogeneity.
Lab Rotation Projects:
My laboratory is currently performing gene profiling of the cells
comprising the neurovascular unit in the central nervous system
(endothelial cells, astrocytes, and perivascular microglia/pericytes.
Specifically, laser capture microdissection of these cells in situ is
being coupled to quantitative, real-time PCR and DNA microarray
platforms. The objective is to determine molecular finger prints of the
neurovascular unit throughout the CNS microvascular tree. As different
vascular beds exhibit unique phenotypes, such an approach will be
critical in identifying why particular CNS regions are prone to diseases
with vascular involvement, such as MS, stroke and Alzheimer's disease.
Selected Publications:
Song L, and Pachter JS. 2004. Monocyte chemoattractant protein-1
alters expression of tight junction-associated proteins in brain
microvascular endothelial cells. Microvasc Res. Jan;67(1):78-89.
Ge S, and Pachter JS. 2004. Caveolin-1 knockdown by small interfering
RNA suppresses responses to the chemokine monocyte chemoattractant
protein-1 by human astrocytes. J Biol Chem. Feb 20;279(8):6688-95.
Song L, and Pachter JS. 2003. Culture of murine brain microvascular
endothelial cells that maintain expression and cytoskeletal association
of tight junction-associated proteins. In Vitro Cell Dev Biol Anim.
Jul;39(7):313-320.
Pachter JS, de Vries HE, and Fabry Z. 2003. The blood-brain barrier
and its role in immune privilege in the central nervous system. J
Neuropathol Exp Neurol. Jun;62(6):593-604. Review.
Andjelkovic AV, Song L, Dzenko KA, Cong H, and Pachter JS. 2002.
Functional expression of CCR2 by human fetal astrocytes. J Neurosci Res.
Oct 15;70(2):219-31.
Dzenko, K.A., Andjelkovic, A.V. and Pachter, J.S. 2001. The chemokine
receptor CCR2 mediates the binding and internalization of monocyte
chemoattractant protein-1 along brain microvessels. J. Neurosci.
21:9214-9223.
Andjelkovic, A.V., Zochowski, M.R., Morgan, F. and Pachter, J.S.
2001. Qualitative and quantitative analysis of monocyte transendothelial
migration by confocal microscopy and three-dimensional image
reconstruction. In Vitro Cell. Devel. Biol. 37:111-120. |
