1. Systems Biology Richard R. Almon Ph.D, Professor Dept of Biological Sciences, College of Arts and Sciences Dept. of Pharmaceutical Sciences, School of Pharmacy Center of Excellence in Bioinformatics and Life Sciences physiology, pharmacology, biochemistry, mathematics

2. In collaboration with Debra C. DuBois Ph.D: Dept of Biological Sciences, College of Arts and Sciences Dept. of Pharmaceutical Sciences, School of Pharmacy genetics, molecular biology, physiology William J. Jusko Ph.D: Dept. of Pharmaceutical Sciences, School of Pharmacy Center of Excellence in Bioinformatics and Life Sciences pharmacokinetics, pharmacodynamics, mathematical modeling

3. What is systems Biology? The study of phenomena that impact the intact organism Multiple levels from Molecular Biology to Systems Physiology Multiple Tissues (liver, muscle, kidney, abdominal fat, lung) Time dynamics Quantitative hypotheses

4. Giant Rat Time Series Time Dynamic Response The Approach:

5. Rotation Projects Cloning a gene by PCR and developing a quantitative assay for that gene (cRNA standards) Isolating total RNA from a set of tissues and quantifying the expression of a gene by real time RTPCR

6. Current Projects Arthritis Anti-inflammatory Pharmacology Circadian Rhythms Diabetes Bioinformatics Asthma

7. Recent Publications Pharmacokinetics, pharmacodynamics and toxicities of methotrexate in healthy and collagen- induced arthritic rats. Liu DY, Lon HK, Wang YL, DuBois DC, Almon RR, Jusko WJ. Biopharm Drug Dispos. 2013 May;34(4):203-14. PMID:23456770 Pharmacokinetics, pharmacodynamics and toxicities of methotrexate in healthy and collagen- induced arthritic rats. Evidence for a glucocorticoid receptor beta splice variant in the rat and its physiological regulation in liver. DuBois DC, Sukumaran S, Jusko WJ, Almon RR.Steroids. 2013 Feb;78(2):312-20. PMID:23257260 Evidence for a glucocorticoid receptor beta splice variant in the rat and its physiological regulation in liver. Effects of high fat feeding on liver gene expression in diabetic goto-kakizaki rats. Almon RR, Dubois DC, Sukumaran S, Wang X, Xue B, Nie J, Jusko WJ. Gene Regul Syst Bio. 2012;6:151-68. PMID:23236253 Effects of high fat feeding on liver gene expression in diabetic goto-kakizaki rats. Glucocorticoid effects on adiponectin expression. Sukumaran S, Dubois DC, Jusko WJ, Almon RR. Vitam Horm. 2012;90:163-86. PMID:23017716 Glucocorticoid effects on adiponectin expression. Pharmacokinetics of salsalate and salicylic acid in normal and diabetic rats. Cao Y, Dubois DC, Almon RR, Jusko WJ. Biopharm Drug Dispos. 2012 Jul 10. doi: 10.1002/bdd.1797.PMID: 22782506 Pharmacokinetic/Pharmacodynamic Modeling of Methylprednisolone Effects on iNOS mRNA Expression and Nitric Oxide During LPS-Induced Inflammation in Rats. Pharmacokinetic/Pharmacodynamic Modeling of Methylprednisolone Effects on iNOS mRNA Expression and Nitric Oxide During LPS-Induced Inflammation in Rats. Sukumaran S, Lepist EI, Dubois DC, Almon RR, Jusko WJ. Pharm Res. 2012 Aug;29(8):2060-9. PMID: 22422321

8. Recent Publications cont. Population pharmacokinetic-pharmacodynamic-disease progression model for effects of anakinra in Lewis rats with collagen-induced arthritis. Liu D, Lon HK, Dubois DC, Almon RR, Jusko WJ. J Pharmacokinet Pharmacodyn. 2011 Dec;38(6):769-86. PMID: 22002845 Modeling diabetes disease progression and salsalate intervention in goto-kakizaki rats. Cao Y, Dubois DC, Sun H, Almon RR, Jusko WJ. J Pharmacol Exp Ther. 2011 Dec;339(3):896-904. PMID: 21903749 Light-dark oscillations in the lung transcriptome: implications for lung homeostasis, repair, metabolism, disease, and drug action..Light-dark oscillations in the lung transcriptome: implications for lung homeostasis, repair, metabolism, disease, and drug action.. Sukumaran S, Jusko WJ, Dubois DC, Almon RR, J Appl Physiol. 2011 Jun;110(6):1732-47. PMID: 21436464 Mechanistic modeling of the effects of glucocorticoids and circadian rhythms on adipokine expression. Sukumaran S, Jusko WJ, Dubois DC, Almon RR. J Pharmacol Exp Ther. 2011 Jun;337(3):734-46.. PMID: 21398515 Mechanistic modeling of the effects of glucocorticoids and circadian rhythms on adipokine expression. Dynamic modeling of methylprednisolone effects on body weight and glucose regulation in rats. Fang J, Dubois DC, He Y, Almon RR, Jusko WJ. J Pharmacokinet Pharmacodyn. 2011 Jun;38(3):293-316. PMID: 21394487 Dynamic modeling of methylprednisolone effects on body weight and glucose regulation in rats. Adipose tissue deficiency and chronic inflammation in diabetic Goto-Kakizaki rats.Adipose tissue deficiency and chronic inflammation in diabetic Goto-Kakizaki rats. Xue B, Sukumaran S, Nie J, Jusko WJ, Dubois DC, Almon RR. PLoS One. 2011 Feb 25;6(2):e17386. PMID: 21364767

13. Modeling Diabetes Disease Progression and Salsalate Intervention in Goto-Kakizaki Rats