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Highlighted Project:
Pharmacodynamics and Pharmacogenomics of Corticosteroids.

    Corticosteroids and numerous other drugs are known to act by altering gene expression with many tissues. Both the beneficial and adverse effects of these agents are the consequence of complex genomic and systemic processes. To study one such model system, the researchers working on one of our funded projects (Jusko, Almon, et al, 2004-2005) have developed an extensive database on the response of experimental animals to the synthetic glucocorticoid, methylprednisolone. The database is derived from adrenalectomized rats treated with different dosing regimens, bolus doses and chronic infusions of the drug. Gene array analysis has or will be carried out on the liver, skeletal muscle, and kidney from these animals with additional tissues available for future analysis. In addition, they have maintained data on animal and organ weights as well as an expanding analysis of blood samples (e.g. glucose, lipid, and amino acid profiles). Similar analyses of intact animals with control of circadian time is ongoing.


Some Publications from this research:
  • Almon RR, DuBois DC, Piel WH, Jusko WJ. The Genomic Response of Skeletal Muscle to Methylprednisolone using Microarrays: Tailoring Data Mining to the Structure of the Pharmacogenomic Time Series, Pharmacogenomics, 5: 525-552 (2004) (Click here for pdf version of paper)

  • Almon RR, DuBois DC, Jin JY, Jusko WJ. Temporal Profiling of the Transcriptional Basis for the Development of Corticosteroid- Induced Insulin Resistance in Rat Muscle, Journal of Endocrinology (2005) 184, 219-232 (Click here for pdf version of paper)

  • Almon RR, DuBois DC, Jin JY, Jusko WJ. The Response of Liver to Methylprednisolone: An Approach to Mining a Rich Microarray Time Series, Journal of American Association of Pharmaceutical Sciences, in press (2005) (Click here for pdf version of paper)

  • Almon RR, DuBois DC, Jin JY, Yao Z, Hazra A, Samtani M, Snyder G, Piel W, Jusko WJ. Development, Analysis, and Use of Pharmacogenomic Time Series for Pharmacokinetic/Pharmacodynamic Modeling of Multi-tissue Polygenic Responses to Corticosteroids, Progress in Pharmacogenetics Research, Nova Science, in press (2005)

  • Almon RR, Lai W, DuBois DC, Jusko WJ. Corticosteroid Regulated Genes in Rat Kidney: Mining Time Series Array Data, Am J Physiol Endocrinol Metab, in press (2005) (Click here for pdf version of paper)