• Biomarker Discovery and Toxicogenomics
• Environmental Sentinel Biomonitor (ESB) Systems
• Reproductive Health and Toxicology

Biomarkers and Toxicogenomics

The Force Health Protection program enhances the Army’s ability to protect military personnel, veterans, and their families from deployment-related illness and injury. An increasingly important aspect of Force Health Protection is operational risk management of toxic and hazardous chemical exposure during deployments. Troops may be exposed to harmful chemicals as a result of accidents, sabotage, hostile military action or environmental pollution. New tools for evaluating the impact of chemical exposures on military personnel during deployments and for monitoring their health afterward are needed.

Biological markers, or biomarkers, are measurable molecular, biochemical or cellular alterations in biological matrices, such as fluids, cells, or tissues that occur in response to hazardous chemical exposure. Since biomarkers can indicate the degree of exposure, biological effects, and susceptibility to disease from hazards that personnel may encounter, they have many potential applications in Force Health Protection and health surveillance (see Table).

Exposure to different toxicants causes distinct patterns of gene expression in the nematode worm, C. elegans. Many of these genes are also found in humans. (Enlarge Image 141 KB)

Despite intensive research over the past decade or so, only a few biomarkers have been identified and validated for use in humans. Part of the reason for this disappointing result is that analytical methods and computational power were inadequate for the task. However, the field of genomics, which deals with discovering and understanding how the totality of genetic information is transformed into a living organism, has produced a number of highly sensitive, high throughput screening technologies that can be used for biomarker discovery. Furthermore, the genomics revolution laid the groundwork for proteomics, a complementary approach which deals with the large scale investigation of protein expression. Coupled with bioinformatics which uses computational methods to analyze the rapidly growing gene and protein databases, these approaches enable the rapid identification of biomolecules and discovery of previously unknown pathways in metabolism and disease processes. Collectively, these approaches are called toxicogenomics. Over the next decade, many biomarkers of exposure, effect, and susceptibility to chemical hazards could be identified using these new technologies.

The USACEHR has an aggressive research program to identify key biomarkers associated with hazardous chemicals encountered by military personnel. Taking advantage of genomics, proteomics and bioinformatics, the USACEHR will conduct experiments on its genome-sequenced animal models to identify novel biomarkers that are also highly conserved (homologous) in humans.

For toxicogenomic biomarkers to be useful and valid, their role in the exposure-disease continuum must be understood. To this end, the research at the USACEHR links common toxicologic endpoints (e.g., pathology), doses, and times to genomic and proteomic responses. Such "phenotypic anchoring" of responses is necessary before a biomarker can be transitioned to human studies and eventually validated for use.

This experimental MEMs can perform several clinical tests using a single drop of blood from a finger stick.

The biomarkers discovered and validated in this research effort will be used in the construction of a prototype microelectromechanical system (MEMS) to measure relevant biomarkers in a cross-sectional study of an exposed human population. Such a device would open the door to rapid and precise monitoring of the exposure of deployed forces to environmental toxicants.