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Kathleen L. McCoy, Ph.D.
Professor

Phone: (804) 828-2305
Dept. Fax: (804) 828-9946
e-mail: kmccoy@vcu.edu
Address:
Department of Microbiology & Immunology
Virginia Commonwealth University
P.O. Box 980678
1217 E. Marshall St., 229 Medical Sciences Building
Richmond, VA 23298-0678
Professional Experience
- B.S.,
1976, St. John Fisher College
- M.S.,
1979, University of Washington
- Ph.D.,
1983, University of Washington
-
Postdoctoral: 1983-1985, L.M.I., National Institutes of Health;
1985-1988, L.C.M.I., National Institutes of Health
Research Interests:
The activation of helper T cells occurs following the
recognition of foreign protein antigens bound to the appropriate Major
Histocompatibility Complex molecules on the cell surface of antigen
presenting cells. Peptide fragments are generated inside antigen-presenting
cells by a mechanism termed processing. In my laboratory, both genetic and
biochemical approaches are being utilized to investigate the regulation and
mechanism of antigen processing. Various aspects of antigen processing,
including a lysosomal cysteine pump, thiols, and proteases, are being
studied in B cells, macrophages, and mutant cell lines. In addition, the
step at which the drug, THC, and the chemical, gallium arsenide, interfere
with antigen processing is being analyzed. Besides antigen processing,
antigen-presenting cells perform other function that are critical for a T
cell response. Occupancy of the T cell antigen receptor alone is usually not
sufficient to stimulate maximally the proliferation and cytokine secretion
by T cells. A second signal, termed co-stimulatory activity, provided by
antigen-presenting cells is also essential. The co-stimulatory signal in
many systems is delivered by plasma membrane proteins expressed by the
antigen presenting cells. Recently, we reported that THC selectively
down-regulates the expression of heat- stable antigen, a co-stimulatory
molecule, on macrophages. The mechanism by which THC decreases the
expression of heat-stable antigen is currently being investigated.
Selected Publications:
McCoy KL. Programmed B and T cell development. Nutr Rev.
1998 Jan;56(1 Pt 2):S19-26. Review.
Lewis TA, Hartmann CB, McCoy KL. Gallium arsenide
differentially affects processing of phagolysosomal targeted antigen by
macrophages. J Leukoc Biol. 1998 Mar;63(3):321-30.
Caffrey-Nolan RE, McCoy KL. Direct exposure to gallium
arsenide upregulates costimulatory activity of murine macrophages. Toxicol
Appl Pharmacol. 1998 Aug;151(2):330-9.
Lewis TA, Hartmann CB, McCoy KL. Gallium arsenide
modulates proteolytic cathepsin activities and antigen processing by
macrophages. J Immunol. 1998 Sep 1;161(5):2151-7.
Clements DJ, Matveyeva M, McCoy KL.
Delta9-tetrahydrocannabinol suppresses macrophage costimulation by
decreasing heat-stable antigen expression. Int J Immunopharmacol. 1998
Aug;20(8):415-28.
McCoy, K.L., M. Matveyeva, S.J.. Carlisle and G.A. Cabral.
Cannabinoid
inhibition of the processing of intact lysozyme by macrophages: Evidence for
CB2 receptor participation. J. Pharmacol. Exp. Ther. 289:1620-1625 (1999).
Matveyeva, M., C.B. Hartmann, M.T. Harrison, G.A. Cabral
and K.L. McCoy.
Delta9-tetrahydrocannabinol selectively increases aspartyl cathepsin D
proteolytic activity and impairs lysozyme processing by macrophages. Int. J.
Immunopharmacol. 22: 373-381 (2000).
Buckley, N.E., K.L. McCoy, E. Mezey, T. Bonner, A. Zimmer,
C.C. Felder, M. Glass and A. Zimmer. Immunomodulation by cannabinoids is
absent in mice deficient for the CB2 cannabinoid receptor. Eur. J. Pharmacol.
396:141-149 (2000).
Harrison, M.T. and K.L. McCoy. Immunosuppression by
arsenic: A comparison of cathepsin L inhibition and apoptosis. Int.
Immunopharmacol. 1:647-656 (2001).
Harrison, M.T., C.B. Hartmann and K.L. McCoy. Impact of in
vitro gallium arsenide exposure on macrophages. Toxicol. Appl. Pharmacol.
186:18-27 (2003).
Gondre-Lewis, T.A., C.B. Hartmann, R.E. Caffrey and K.L.
McCoy. Gallium arsenide exposure impairs splenic B cell accessory function.
Int. Immunopharmacol. 3:403-415 (2003).
Becker, S.M. and K.L. McCoy. Gallium
arsenide selectively upregulates inflammatory cytokine expression at
exposure site. J. Pharmacol. Exp. Ther. 307:1045-1053 (2003).
Chuchawankul, S., M. Shima, N.E.
Buckley, C.B. Hartmann and K.L. McCoy. Role of cannabinoid receptors in
inhibiting macrophage costimulatory activity. Int. Immunopharmacol.
4:265-278 (2004).
Hartmann, C.B. and K.L. McCoy. Gallium
arsenide exposure impairs processing of particulate antigen by macrophages:
Modification of the antigen reverses the functional defect. Life Sci.
75:485-498 (2004).
Hartmann, C.B., M.T. Harrison and K.L.
McCoy. Immunotoxicity of gallium arsenide on antigen presentation:
Comparative study of intratracheal and intraperitoneal exposure routes. J.
Immunotoxicol. 2:1-9 (2005).
Creasy, B.M., C.B. Hartmann, F.K.
Higgins White and K.L. McCoy. New assay using fluorogenic substrates and
immunofluorescence staining to measure cysteine cathepsin activity in live
cell subpopulations. Cytometry Part A. 71A:114-123 (2007). |