PRIMARY FACULTY MEMBER
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Jefferey Harrison, Ph.D. Assoc. Professor Phone: 352-392-3227 Office: R5-254 Academic Research Bldg. Email: jharriso@ufl.edu Publications: Search PubMed |
Research Interests
Our laboratory has focused its studies on understanding the functional significance of chemokine networks in the central nervous system. Specific attention has been given to the unique chemokine fractalkine (FKN/CX3CL1). This neuronal-expressed molecule interacts with its receptor, CX3CR1, which is prominently expressed by microglia. We have and continue to study these genes in animal models of disease, including nerve injury and brain cancer, cellular signaling mechanisms, and structure-function relationships that include development and pharmacological characterization of CX3CR1 selective agents.
Selected publications:
Harrison, J.K., Y. Jiang, S. Chen, Y. Xia, D. Maciejewski, R.K.
McNamara, W.J. Streit, M.N. Salafranca, S. Adhiari, D.A. Thompson, P. Botti, K.B. Bacon, L. Feng. Role for neuronally-derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia. Proc Natl Acad Sci, USA 95:10896-10901, 1998.
Harrison, J.K., A. M. Fong, P.A.W. Swain, S. Chen. Y.-R.A.
Yu, M.N. Salafranca, W.B. Greenleaf, T. Imai, D. D. Patel. Mutational analysis of the fractalkine chemokine domain: Basic amino acid residues differenttially contribute to CX3CR1 binding, signaling, and cell adhesion. J Biol Chem 276:21632-21641, 2001.
Chen, S., D. Luo, W.J. Streit, J.K. Harrison. TGF-� upregulates
CX3CR1 expression and inhibits fractalkine stimulated signaling in rat microglia. J Neuroimmunol 133:46-55, 2002.
Davis, C.D., V. Zujovic, and J.K. Harrison. Viral macrophage
inflammatory protein-II and fractalkine (CX3CL1) chimeras identify molecular determinants of affinity, efficacy, and selectivity at CX3CR1. Mol Pharmacol 66:1431-1439, 2004.
Chen, S., D.L. Tuttle, J.T. Oshier, H.J. Knot, W.J. Streit, M.M. Goodenow, and J.K. Harrison. Transforming growth factor-�1 increases CXCR4 expression, stromal derived factor-1 α-stimulated signaling and human immunodeficiency virus-1 entry in human monocyte-derived macrophages. Immunology 114:565-574, 2005.
Davis, C.D. and J.K. Harrison. Pro326 in the C-terminus of
murine CX3CR1 prevents G-protein and PI3-Kinase dependent stimulation of Akt and ERK in CHO cells. J Pharmacol Exp Ther 316:356-367, 2006.
An additional area of investigation that is receiving considerable attention by our group resulted from a genomic expression analysis of the response to peripheral nerve injury. Hn1 (hemopoietic- and neurologic-expressed sequence 1) is a very unique molecule that is highly expressed during development and is strongly up-regulated in injured motoneurons that normally undergo efficient repair of their severed axons, and successfully reinnervate target skeletal muscle tissue. This gene is also highly expressed in a variety of cancer cell lines and in vivo tumor models. Experiments in the lab are directed toward understanding the function of this gene in development and disease, and include animal model, cellular, and structural biological approaches.
Zujovic, V., D. Luo, H.V. Baker, M.C. Lopez, K.R. Miller, W.J.
Streit, and J.K. Harrison. The facial motor nucleus transcriptional program in response to peripheral nerve injury identifies Hn1 as a regeneration associated gene. J Neurosci Res 82:581-591, 2005.
Location: http://www.med.ufl.edu/pharm/faculty/harrison.shtml