Biomedical Sciences Graduate Program |
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Charles
J.
Flickinger
Degree(s): M.D. Graduate School: Harvard Medical School Primary Appointment: Professor Emeritus of Cell Biology Research Interests: Male reproductive cell biology: testis, epididymis, sperm, antigens. Email Address: cjf@virginia.edu |
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Research Description My laboratory is investigating the secretion of proteins in the epididymis and
the male sex accessory glands. Proteins secreted by the epididymal epithelium,
for example, are believed to play an important role in the post-testicular maturation
of sperm, including acquisition of fertilizing ability. Currently we are studying
natural antimicrobial proteins, part of the innate immune system, that are secreted
by the epididymis and other parts of the male reproductive system. My laboratory
cloned and characterized a novel sperm-associated isoantigen, E-3, which has defensin-
and lectin-like motifs and is expressed in the epididymis, and we have determined
that several defensins and a cathelicidin are expressed in different parts of
the male reproductive tract in rats. One aim of our present work is to identify
novel antimicrobial proteins in fluids of the epididymis and sex accessory glands.
In addition, we are studying changes in the repertoire of defensins and cathelicidins
during development of the male reproductive system, and we are investigating how
the expression patterns of various antimicrobial proteins are regulated.
We are also involved in characterizing and cloning sperm antigens, in collaboration
with Dr. John Herr. We are using immunocytochemistry to localize antigens in
spermatozoa and in the testis, and make use of both northern analysis and immunocytochemistry
to perform tissue specificity studies of putative gamete-specific antigens.
We have also studied testicular gene expression with in situ hybridization methods
to detect specific germ cell mRNAs. A long-standing research interest in my laboratory is study of the morphologic,
immunologic, and physiologic effects of obstruction of the male reproductive
tract. Vasectomy is a common means of contraception in men, but questions remain
about its reversal, because an individual may remain infertile despite successful
surgical reconnection of the vas deferens. Aims of this research are to determine
the nature of changes after obstruction of the male tract and to determine the
extent to which these are reversible by subsequent repair. We have concentrated
on post-obstruction antibody responses in a rat model system assessed by ELISA,
identification of specific sperm autoantigens using gel electrophoresis and
western blotting techniques, and morphological studies of the testis and epididymis
using light and electron microscopy. Emphasis has been on analysis of sperm
autoantigens by two dimensional gel electrophoresis and blotting, microsequencing,
and cloning of dominant autoantigens. A long term aim is to discern the relation
between the immunologic response to specific antigens and testicular alterations
and/or infertility. |