Wenzhong Xiao
Stanford University School of Medicine, USA
Title: Of men and not mice: Comparative genomic analysis of human diseases and mouse models
Biography
Biography: Wenzhong Xiao
Abstract
A cornerstone of modern biomedical research is the use of mouse models to explore basic disease mechanisms, evaluate new therapeutic approaches and make decisions to carry new drug candidates forward into clinical trials. However, few of these human trials have shown success. Here, we systematically compared the genomic response from publically available datasets of patients of different acute inflammatory diseases and corresponding murine models; and showed that, although inflammation from different etiologies resulted in highly similar genomic responses in humans, the responses in mouse models correlated poorly with the human disease and also with one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts. Our findings suggest that a disease model shall be carefully (re) examined to see how well it reproduces the human disease at the molecular level because virtually every drug and drug candidate target gene product(s). In addition, our comparisons of trauma patients reveal genomic signature between complicated and uncomplicated outcomes, and specific mediators which serve as predictive biomarkers for the development of targeted treatments at the bedside.
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