2008 Faculty Researchers

Gary F. Clark, Ph.D.

Regulation of potential immune responses directed against human and murine gametes

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Department

Obstetrics, Gynecology and Women’s Health

Office Location

N625 and M667 MSC

Phone #:

Office: (573) 884-3134
Fax: (573) 882-9010

Summary

Protection of the gametes and the developing fetus from potential immune responses is essential for reproduction. What is particularly interesting about both male and female gametes is that some of their proteins are foreign to the immune system. This finding suggests that a very powerful system for inducing tolerance to these glycoproteins exists in both the male and female reproductive tracts.

The major hypothesis in our laboratory is that specific carbohydrate sequences linked to many glycoproteins are responsible for mediating immune tolerance in the reproductive system. Unfortunately, our data also indicate that aggressive tumor cells and many human pathogens including HIV-1, Helicobacter pylori, and schistosomes are also either mimicking or acquiring these carbohydrate sequences, enabling them to resist the human immune response. In essence, these pathogens and tumor cells have coupled their survival to our survival by integrating themselves into this protective system that facilitates sexual reproduction.

We have identified specific oligosaccharide sequences that we believe are mediating this effect in humans and mice. We are currently coupling these oligosaccharides to inert protein backbones to form “neoglycoproteins”. Our major goals include: (i) to determine if these neoglycoproteins can manifest immunosuppressive effects in vitro; and (ii) to define the signal transduction pathway(s) that promote the protection of the gametes. If some method can be developed to block this system temporarily, it may be possible to attack and destroy persistent pathogens and tumor cells that currently cannot be addressed using conventional immunotherapeutic strategies due to this protective effect.

There are some other rather important implications of this research effort. They can be found at the following links:

• http://www.eurekalert.org/pub_releases/2007-12/uom-nss121307.php
• http://www.residentandstaff.com/reuters_article.asp?id=20071231scie001.html
• http://molehr.oxfordjournals.org/cgi/reprint/3/1/5.pdf

Students will actively participate with our enthusiastic research team to perform in vitro assays on specific immune cell subsets in collaboration with Dr. David Lee of the Department of Molecular Microbiology and Immunology These studies will expose the student to cell culture techniques, methods of immune cell isolation and the current thinking about the immunological aspects of reproduction, pathogenesis and tumorigenesis. Students are expected to present their work at the School of Medicine Research Day as required.