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duboisDr. Debra C. DuBois

Research Associate Professor
Hochstetter 117
Phone: (716) 645-4907
E-mail: dubois@nsm.buffalo.edu
Further research info

Ph.D. University at Buffalo

Research Summary

Glucocorticoids are a class of steroid hormone which regulate systemic gluconeogenesis. In addition, glucocorticoids are potent suppressors of immune system function. Synthetic glucocorticoids are widely used clinically as immunosuppressant and anti-inflammatory drugs. However, many of the side-effects of these agents result from their gluconeogenic effects on muscle, liver, kidney, and adipose tissue. A primary mechanism of action of glucocorticoids involves modulation of gene expression. The goal of our work is to apply a pharmacodynamic approach to glucocorticoid modulation of gene expression at the transcriptional and translational levels. A primary focus concerns the role of receptor autoregulation in steroid response to various steroid dosing regimens.

Selected Publications

  • Yao, Z., DuBois, D.C.., Almon, R.R., and Jusko, W.J. Pharmacodynamic/ pharmacogenomic modeling of the insulin resistant genes in rat muscle after methylprednisolone treatment: Exploring regulatory signaling cascades. Gene Reg. Sys. Biol., 2: 141-161, 2008.
  • Hazra, A., DuBois, D.C., Almon, R.R., Snyder, G.H., and Jusko, W.J. Pharmacodynamic modeling of acute and chronic effects of methylprednisolone on hepatic urea cycle genes in rats. Gene Reg. Sys. Biol., 2: 1-19, 2008.
  • Yang, E., Almon, R.R., DuBois, D.C., Jusko, W.J., and Androulakis, I.P. Extracting global System dynamics of corticosteroid genomic effects in rat liver. J. Pharmacol. Exp. Therapeutics. 324: 1243-1254, 2008
  • Yao Z, DuBois DC, Almon RR, Jusko WJ. Pharmacokinetic/pharmacodynamic modeling of corticosterone suppression and lymphocytopenia by methylprednisolone in rats. J Pharm Sci. 2008 Jul;97(7):2820-32.
  • Hazra A, Pyszczynski NA, DuBois DC, Almon RR, Jusko WJ. Modeling of corticosteroid effects on hepatic low-density lipoprotein receptors and plasma lipid dynamics in rats. Pharm Res. 2008 Apr;25(4):769-80.
  • Yao, Z., Hoffman, E.P., Ghimbovschi, S., DuBois, D.C., Almon, R.R., and Jusko, W.J. Mathematical modeling of corticosteroid pharmacogenomics in rat muscle following acute and chronic methylprednisolone dosing. Mol. Pharm., 5: 328-339, 2008.
  • Hazra A, Pyszczynski N, DuBois DC, Almon RR, Jusko WJ. Modeling receptor/gene-mediated effects of corticosteroids on hepatic tyrosine aminotransferase dynamics in rats: dual regulation by endogenous and exogenous corticosteroids. J Pharmacokinet Pharmacodyn.: 34(5):643-67, 2007
  • Hazra A, Pyszczynski N, DuBois DC, Almon RR, Jusko WJ. Pharmacokinetics of methylprednisolone after intravenous and intramuscular administration in rats. Biopharm Drug Dispos: 28(6):263-73, 2007
  • Almon RR, DuBois DC, Yao Z, Hoffman EP, Ghimbovschi S, Jusko WJ. Microarray analysis of the temporal response of skeletal muscle to methylprednisolone: comparative analysis of two dosing regimens. Physiol Genomics. 30(3):282-99, 2007
  • Yang E, Simcha D, Almon RR, Dubois DC, Jusko WJ, Androulakis IP. Context specific transcription factor prediction. Ann Biomed Eng. 35(6):1053-67, 2007
  • Androulakis IP, Yang E, Almon RR. Analysis of time-series gene expression data: methods, challenges, and opportunities. Annu Rev Biomed Eng. 9:205-28, 2007
  • Yao Z, Zhao B, Hoffman EP, Ghimbovschi S, DuBois DC, Almon RR, Jusko WJ. Application of scaling factors in simultaneous modeling of microarray data from diverse chips. Pharm Res. 24(4):643-9, 2007
  • Almon RR, DuBois DC, Jusko WJ. A microarray analysis of the temporal response of liver to methylprednisolone: a comparative analysis of two dosing regimens. Endocrinology. 148(5):2209-25, 2007
  • Hazra A, DuBois DC, Almon RR, Jusko WJ. Assessing the dynamics of nuclear glucocorticoid-receptor complex: adding flexibility to gene expression modeling. J Pharmacokinet Pharmacodyn. 34(3):333-54, 2007