? ? Caldera Pharmaceutical's will use their unique, R&D100-award-winning Reagentless Pharmacoproteomic Measurement (RPM) high-throughput technology to identify biomarkers of response to environmental stressors (BRES). Caldera developed RPM in collaboration with Los Alamos National Laboratory. RPM allows the identification and measurement of BRES consisting of protein-metal adducts and metabolites. We propose to develop BRES to define patterns of response to benefit the Gene Environment Initiative, focusing on xenobiotic biotransformation in human disease like Autism. Our BRES will lead to reliable measurements of exposures, which can be correlated with variable susceptibility to metal toxicity in the human population. This provides valuable information involving metabolic pathways for the Gene Environment Initiative (GEI). We will measure exposure to metal stressors in biospecimens by developing BRES that can identify exposure to particular chemical forms of toxic metals. Protein:metal adducts formed in individual patients may be correlated to genetic differences regulating metallothionein or other metallome proteins thought to be related to autism. RPM can monitor simultaneous exposure to toxins, such as arsenic, cadmium, lead, and mercury (thimerasol), as well as exposure to essential metals (zinc, iron, selenium, etc.). Individuals with autism may have varying genes that biotransform and detoxify metals differently, leading to varying accumulation and disease susceptibility. ? ? ? ?
