Molecular toxicology of trace metals, metal effects on heme and porphyrin metabolism, biological markers of metal exposure, gene-metal interactions
Molecular Mechanisms of Metal Toxicity
Students in our laboratory use animal models and cultured cells from kidney, brain or other tissues to define signaling pathways involved in metal toxicity. Particular interest focuses on cellular mechanisms by which metals cause cell injury by promoting oxidative stress, causing inflammation, or by increasing the susceptibility of cells to apoptosis, an underlying event in chronic degenerative diseases. Cell culture techniques, gene expression assays, autoradiography, and microarray-based assays are principal techniques used in these studies.
Biomarkers of Metal Exposures
Biomarkers are metabolites in the blood or urine that are altered by toxicant exposure. Toxic metals such as mercury, arsenic and lead alter the concentrations of metabolites called porphyrins in the urine. Changes in the urinary porphyrin excretion pattern can be used as specific biomarkers of exposure and ensuing toxicity to these metals. Students in our laboratory participate in studies to validate porphyrin excretion patterns as a predictive biomarker of mercury-related neurotoxicity in both adult and children human populations with mercury exposure from different sources. Students involved in these studies utilize column chromatography, atomic absorption spectrofluormetry and HPLC techniques for metal and porphyrin analyses.
Genotoxicity of Metal-related Disorders
A major research focus for students in our laboratory is identifying genetic polymorphisms that underlie increased susceptibility to metal toxicity. Particular interest focuses on mercury-related neurological and behavioral disorders in children and the elderly, including autism, ADHD and age-related dementia. Students participating in these studies identify candidate genes that are likely to be involved in these disorders, perform DNA genotyping assays using real time PCR or SNP-chip techniques to evaluate gene polymorphisms and gene frequencies, and employ biostatistical and bioinformatics procedures to determine if specific polymorphisms underlie increased sensitivity to mercury or other metal(s) in behavioral, cognitive or motor function deficits associated with these disorders.