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Participant Profiles

ORISE Intern Gains Chemical Warfare Insights through Molecular Toxicology Research

ORISE intern Kriston McGary arrived at the U.S. Army Medical Research Institute of Chemical Defense (MRICD) shortly after receiving his bachelor's degree in biology from Bryan College in Dayton, Tenn., in the spring of 2000. While at MRICD, he was mentored by Dr. John Schlager, head of the Molecular Toxicology Team, and worked with Dr. James Dillman, III, who was a National Research Council Postdoctorate fellow also under Schlager’s mentorship and who is now a permanent MRICD principal investigator.

MRICD is the Department of Defense lead laboratory for medical chemical defense research and, as such, develops prophylactics, pretreatments, and antidotes, and provides instruction to protect and treat the warfighter on a chemical battlefield. To accomplish this mission, scientists at the MRICD conduct research to define the biological systems affected by the agent, identify any short- and mid-term consequences of exposure, and explore methods of medical intervention.

MRICD is the Department of Defense lead laboratory for medical chemical defense research and, as such, develops prophylactics, pretreatments, and antidotes, and provides instruction to protect and treat the warfighter on a chemical battlefield. To accomplish this mission, scientists at the MRICD conduct research to define the biological systems affected by the agent, identify any short- and mid-term consequences of exposure, and explore methods of medical intervention.

The focus of Dillman’s research has been to identify potential prophylactic and therapeutic targets for further research and development through the use of proteomics to define the molecular and cellular consequences of chemical warfare agent exposure.

McGary helped in the molecular characterization of the p38 signaling pathway. This pathway is a known cellular stress-response pathway that the team discovered is activated by exposure of keratinocytes to vesicating doses of sulfur mustard (HD). This pathway is activated in a dose- and time-dependent manner in response to HD. Pharmacologic inhibition of p38 activity decreased cytokine production, as measured by a new multiplex assay, by 70%. The cytokines IL-8, IL-6, IL-1Beta, and TNF-alpha were measured in the assay. Thus, inhibition of this pathway significantly decreases the production of inflammatory cytokines in response to sulfur mustard exposure.  Identification of this pathway as a key player in HD-induced inflammation provides a new series of potential drug targets in the development of medical countermeasures against HD exposure.

This research garnered Dillman and his coauthors, including McGary, best poster honors at this year’s Society of Toxicology national meeting. Their winning poster presentation "Upregulation of Cytokine Release by Sulfur Mustard Exposure is Mediated by the p38 MAP Kinase Signaling Pathway" was one of over thirty presented in the session.

According to MRICD’s commander, Col. James Romano, “Jim and Kris's application of proteomics to the problem of poisoning by mustard gas has led to remarkable new insights into how to potentially treat mustard. It also adds to the basic body of knowledge of skin inflammation.”  

Schlager echoes Romano’s sentiments. “This research on the activation of cellular inflammation pathways in culture skin cells after sulfur mustard exposure is one example of the work of Dr. Dillman and his research group that has advanced both the basic and applied research in the treatment approaches to human skin sulfur mustard exposure.” 

McGary left MRICD in July of 2002 to pursue a graduate degree at the University of Texas at Austin, where he has found his experience as an MRICD ORISE participant to be invaluable.

“The ORISE program placed me in a laboratory where I learned how to approach scientific and medical questions using techniques from molecular biology, genomics, and proteomics. This experience accelerated my preparation for future studies and has significantly improved my perspective as a first year graduate student,” said McGary.

“I have been able to go straight into a lab and make progress toward my research goals from the first day. I feel much better prepared than many of the students who have come straight from an undergraduate program. The congenial atmosphere at MRICD allowed me to develop research skills in a non-threatening environment, which gave me the confidence I need to take on new projects here at the University of Texas at Austin."