Jing Zhang is a recent PhD graduate from Carleton University under Dr. Kenneth Storey’s supervision and joined Dr. Valerie Langlois’ group as a Post-doctoral fellow in the fall of 2013. His field is molecular physiology and previous work includes investigating molecular mechanisms behind survival adaptions under extreme environmental conditions in various stress tolerant animal models. Currently, he is focusing on exploring the potential of hair follicle as a diagnostic tool for military activity-related medical conditions including traumatic brain injury (TBI) and operational stress disorders using transcriptomic approaches.
Military personnel commonly exposed to operational stressors (example, intense physical exertion, sleep deprivation and fatigue) during both training activities and combat operations, which are often, associated with mental health disorders including depression and post-traumatic stress disorder. As psycho-physiological changes driven by molecular mechanisms, it is useful to assess corresponding adaptations in gene expression profiles for a better understanding of such responses. Thus, we explored human hair follicles as a robust and accessible biomarker system for both characterization and diagnostic purposes. Four healthy male volunteers performed a 2-week period of high-intensity interval training (HIIT) as an easily quantifiable and reproducible physical stress model. RNA-sequencing was conducted on an Illumina MiSeq platform using the total RNA libraries prepared from the hair follicles collected from the vertex area of the scalp pre- and post-HIIT. The resulting RNA sequences aligned to the human genome. Differential expression (DE) analyzed for protein coding RNA (mRNA), miRNA and long non-coding RNA (lncRNA). Gene ontology (GO) term analysis also conducted. Based on the DE mRNA results, the GO term enrichment showed 192 positively affected terms (example, hormonal control), while 387 (example, immune system process) were negatively enriched upon HIIT. Regarding to miRNA, 48 related GO terms (example, antioxidant response) enriched. We also identified 249 differentially expressed lncRNAs including those involved in RNA processing (example, RMRP). Overall, this study demonstrates that human hair follicles are a valuable resource inproviding molecular signatures linked to operational stress disorders.
The incidence of allergy/immunotoxicity-related post-market adverse events associated with medical devices is increasing. Biomarkers are commonly used in toxicology for risk assessment and clinically as diagnostic and monitoring tests. We developed a new in vitro model where human peripheral blood mononuclear cells (PBMC) isolated from four healthy donors were used to identify biomarkers that specifically respond to metallic allergens. Cells were exposed to well-known human metallic allergens and non-allergens for 24 hours. The cell surface markers were measured by employing flow cytometry. A primary goal was to determine whether the two cell types are transferable from the dendritic cell (DC) to the PBMC due to the clinical relevance of the PBMC. Of the 12 cell surface markers following the first tier selection, the expression of CD1X and CD86 on PBMC was confirmed and 3 other novel biomarkers were discovered (CD2X, CD3X and CD4X). The expression of CD1X on PBMCs was down-regulated significantly following exposure to three metallic allergens (cobalt (II) chloride, nickel (II) sulfate, potassium dichromate (VI)) while the expression remained the same when exposed to two metallic non-allergens (lead (IV) acetate, magnesium (II) chloride) compared to untreated PBMCs. Data from the all four donors showed the same pattern and the statistical value of CD1X alone yielded a p value<0.0001 and an accuracy greater than 95% based on receiver operating characteristic (ROC) analysis. We found the consistency of CD1X performance in PBMC even greater compared to that in DC. Data indicate that CD1X shows promise for use as a pre-clinical biomarker for screening potential allergenic responses to metal-containing devices. Further validation studies are planned.