CINRG: Systems Biology of Glucocorticoids in Muscle Disease
Final rept. 21 Sep 2009-20 Sep 2013
CHILDREN'S RESEARCH INST WASHINGTON DC CENTER FOR GENETIC MEDICINE
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We developed two computational network reconstruction methods, linear state space model and dynamic Bayesian network, to infer transcriptional networks using the rat acute transcriptional time series of bolus administration of glucocorticoids. This time series was re-profiled using Illumina gene expression BeadChip for a much broader coverage. We have successfully used staged injection models to induce asynchronous regenerations in normal mouse muscles. Using laser capture microscopy and gene expression microarray profiling, we extensively analyzed muscle tissues dissected from the injection sites and in between regions in the 4 day and 10 day reinjury series. The results showed inappropriate crosstalk in the muscles from in between areas due to neighboring asynchronous regenerations in both injection series. We showed that daily administration of Prednisolone suppressed inappropriate crosstalk in the muscle regions between asynchronously remodeling areas. We have been awarded several new grants focusing on studying glucocorticoid mechanism in treating DMD and asthma. Two doctoral students graduated or are graduating under partial support from this grant.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research
- Numerical Mathematics