Systems Biology

Richard R. Almon Ph.D, ProfessorDept 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

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 Sciencespharmacokinetics, pharmacodynamics, mathematical modeling

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

Giant Rat Time Series

Time

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The Approach:

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

Current Projects

• Arthritis• Anti-inflammatory Pharmacology• Circadian Rhythms• Diabetes• Bioinformatics• Asthma

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

• 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

• 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

• Glucocorticoid effects on adiponectin expression. Sukumaran S, Dubois DC, Jusko WJ, Almon RR. Vitam Horm. 2012;90:163-86. PMID:23017716

• 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.• Sukumaran S, Lepist EI, Dubois DC, Almon RR, Jusko WJ.• Pharm Res. 2012 Aug;29(8):2060-9. PMID: 22422321

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.. 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

• 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: 21394487Adipose 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

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