Laboratory
of Chemokine Research
Welcome to the Karpus
Lab
Scroll down to read
about our research program
William J. Karpus, Ph.D.
Professor
Departments of Pathology and
Microbiology Immunology
Northwestern University
Feinberg School of Medicine
Lab Members:
Seated: Rashida Lathan and Will DePaolo;
Standing: Adam
Elhofy , Jami Bennett, and Rukiye-Nazan
Dogan
Current Research Program:
The central theme of my research program is the role of chemokines and chemokine
receptors in the regulation of autoimmune disease, chronic viral diseases,
mucosal immunity and tolerance to gut pathogens. The three major research projects are listed below.
1.
We study the pathogenesis and regulation of experimental
autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis
(MS).
EAE follows a relapsing-remitting course of paralysis and is characterized
by lymphocyte and monocyte infiltrates of the central nervous system (CNS) with
areas of demyelination. It is clear that
similarities exist in both clinical course and histopathology between relapsing
forms of EAE and MS and this allows us to develop new therapeutic strategies
for human disease. As a result of this
autoimmunity, T lymphocytes migrate from the peripheral lymphoid tissue and
blood to the brain and spinal cord. This
is a central feature in the pathogenesis of both MS and EAE. A number of factors, including
cell-associated integrins and soluble chemokines, regulate the migration or
trafficking of T cells to tissue sites.
We have identified a number of chemokines and chemokine receptors
responsible for paralytic disease induction and progression. Current projects include:
a.
Chemokine regulation of dendritic cell trafficking in EAE
development, remission and relapse.
b.
Chemokine regulation of T cell effector function.
c.
Chemokine regulation of T cell trafficking during remission
and disease relapses.
d.
Targeting of chemokines for novel therapeutic intervention.
e.
Epitope spreading and lymphocyte trafficking.
Funded
by NIH R01 NS034510
2.
Theiler’s murine encephalomyelitis virus (TMEV)
chronically infects mice and induces a progressive paralytic disease resembling
MS. In contrast to EAE, the disease
course is chronic progressive and un-remitting.
However, lymphocytes and monocytes infiltrate the brain and spinal cord
and induce demyelination. We have
identified chemokines, MCP-1 in particular, responsible for the induction of
paralytic disease. Current projects
include:
a.
Chemokine receptor regulation of chronic disease
progression.
b.
Chemokine regulation of resultant autoimmune responses.
c.
Chemokine regulation of viral persistence.
Funded by NIH P01
NS023349
3.
There is a growing body of evidence that indicates aberrant
chemokine receptor expression by both human B cell and T cell lymphomas and
leukemias. Similarly, chemokine ligand
expression as been noted in human B cell, T cell, and Hodgkin’s
lymphoma. These findings raise the
possibility that chemokines and their receptors may be involved in lymphoma
cell movement between lymphoid as well as non-lymphoid sites. The idea that chemokines and their receptors
functionally direct the migration of lymphoma cells to lymphoid and
extra-lymphoid tissues has not been formally tested either clinically or
preclinically. Using a mouse model of B cell lymphoma we propose to test the
hypothesis that chemokine expression in lymphoid and non-lymphoid tissue
regulates the migration of lymphoma cells expressing specific chemokine
receptors to those particular tissues.
Funded by the Mazza
Foundation
Selected Publications:
DePaolo, R.W., R. Lathan,
B.J. Rollins, and W.J. Karpus. The
Chemokine CCL2 Is Required for Control of Murine Gastric Salmonella enterica
Infection. Infection and Immunity 73:
6514-6522, 2005.[Reprint]
Karpus, W.J. Chemokines and central nervous system
disorders. In Current Clinical
Neurology: Inflammatory Disorders of the
Nervous System: Pathogenesis,
Immunology, and Clinical Management, A. Minagar and J.S. Alexander (eds.). Humana Press, 2005.[Reprint]
Elhofy, A., J. Wang, M. Tani, B.T. Fife, K.J. Kennedy, J.
Bennett, D. Huang, R.M. Ransohoff, and W.J. Karpus. Transgenic expression of CCL2 in the central
nervous system prevents experimental autoimmune encephalomyelitis. J. Leukoc. Biol. 77: 229–237,
2005.[Reprint]
Carpentier, P.A., W.S.
Begolka, J.K. Olson, A. Elhofy, W.J. Karpus, and S.D. Miller. Differential Activation of Astrocytes by
Innate and Adaptive Immune Stimuli. Glia 49:360–374, 2005.[Reprint]
DePaolo, R.W., R. Lathan,
and W.J. Karpus. CCR5 Regulates High
Dose Oral Tolerance by Modulating CC Chemokine Ligand 2 Levels in the
GALT. J. Immunol. 173: 314–320, 2004.[Reprint]
Dogan, R.E. and W.J.
Karpus. Chemokines and chemokine
receptors in autoimmune encephalomyelitis as a model for central nervous system
inflammatory disease regulation. Frontiers in Bioscience 9: 1500-1505,
2004.[Reprint]
DePaolo, R.W., B.J.
Rollins, W. Kuziel, and W.J. Karpus. High dose oral tolerance is dependent on the
chemokine CCL2 and its receptor CCR2. J.
Immunol. 171: 3560-3567, 2003.[Reprint]
Monaghan SA, Peterson LC,
James C, Marszalek L, Khoong A, Bachta DJ, Karpus WJ, Goolsby CL. Pan B-cell markers are not redundant in
analysis of chronic lymphocytic leukemia (CLL).
Clinical Cytometry 56B:30-42,
2003.[Reprint]
Bennett, J.L., A. Elhofy,
M.C. Dal Canto, M. Tani, R.M. Ransohoff, and W.J. Karpus. CCL2 transgene expression in the central
nervous system directs diffuse infiltration of CD45highCD11b+
monocytes and enhanced Theiler’s murine encephalomyelitis virus-induced
demyelinating disease. J. NeuroVirol. 9:623-636, 2003.[Reprint]
Karpus, W.J., B.T. Fife
and K.J. Kennedy. Immunoneutralization
of chemokines for the prevention and treatment of central nervous system
autoimmune disease. Methods 29: 362-368, 2003.[Reprint]
Elhofy, A., K.J. Kennedy,
B.T. Fife and W.J. Karpus. Regulation of
experimental autoimmune encephalomyelitis by chemokines and chemokine
receptors. Immunol. Res. 25: 167-175,
2002.[Reprint]
Karpus, W.J. Chemokines in central nervous system
disorders. J. Neurovirol. 7:493-500,
2001.[Reprint]
Karpus, W.J. and R.M.
Ransohoff. Cutting Edge Commentary:
Chemokine Regulation of Experimental Autoimmune Encephalomyelitis: Temporal and
Spatial Expression Patterns Govern Disease Pathogenesis. J. Immunol. 161: 2667-2671, 1998.[Reprint]
Kennedy, K.J., R.M.
Strieter, S.L. Kunkel, N.W. Lukacs, and W.J. Karpus. Acute and relapsing experimental autoimmune
encephalomyelitis are regulated by differential expression of the CC chemokine
macrophage inflammatory protein-1alpha and monocyte chemotactic protein-1. J.
Neuroimmunol. 92. 98-108 1998.[Reprint]
Karpus WJ, Kennedy KJ,
Kunkel SL, Lukacs NW Monocyte Chemotactic Protein 1 Regulates Oral
Tolerance Induction by Inhibition of T Helper Cell 1-related Cytokines. J. Exp.
Med. 187:733-741,1998.[Reprint]
Karpus, W.J. and Kennedy,
K.J. MIP-1a and MCP-1 differentially regulate acute and relapsing
autoimmune encephalomyelitis as well as Th1/Th2 lymphocyte differentiation. J. Leukoc. Biol. 62:
681-687, 1997.[Abstract]
[2001 Dolph Adams Award]
Kennedy, K.J., Smith,
W.S., Miller, S.D., and Karpus, W.J. Induction of antigen-specific
tolerance for the treatment of ongoing, relapsing autoimmune encephalomyelitis:
a comparison between oral and peripheral tolerance. J. Immunol. 159: 1036-1044, 1997.[Reprint]
Karpus, W.J., Lukacs,
N.W., Kennedy, K.J., Smith, W.S.,
Pope, J.G., Karpus, W.J.,
VanderLugt, C., and Miller, S.D. Flow cytometric and functional analyses
of central nervous system-infiltrating cells in SJL/J mice with Theiler's
virus-induced demyelinating disease. Evidence for a CD4+ T
cell-mediated pathology. J. Immunol.
156: 4050-4058, 1996.[Reprint]
Karpus, W.J., Lukacs,
N.W., McRae, B.L., Strieter, R.M., Kunkel, S.L., and Miller, S.D. An
important role for the chemokine macrophage inflammatory protein-1 alpha in the
pathogenesis of the T cell-mediated autoimmune disease, experimental autoimmune
encephalomyelitis. J. Immunol. 155:
5003-5010, 1995.[Reprint]
Karpus, W.J., Pope, J.G.,
Peterson, J.D., Dal Canto, M.C., and Miller, S.D. Inhibition of Theiler's
virus-mediated demyelination by peripheral immune tolerance induction. J. Immunol. 155: 947-957, 1995.[Reprint]
McRae, B.L., Nikcevich,
K.M., Karpus, W.J.,
Northwestern Links:
