Jayalakshmi Sridhar
Assistant Professor

Organic Chemistry Lecture, Drill, and Laboratory (CHEM 2210, 2210D, 2220, 2220D, 2230L, 2240L and 4320LB)

2012-present, Assistant Professor of Chemistry
2009-2012, Research Associate, Xavier University of Louisiana, New Orleans, LA,       USA.
2005-2008, Visiting Researcher, Department of Bioengineering, University of        California, Riverside, CA, USA
2002-2005, Postdoctoral position, Department of Neurosciences and Lombardi      Comprehensive Cancer Center, Georgetown University, Washington DC, USA.
1999-2001, Research Associate, Indian Institute of Technology, Chennai, India.
1998- Ph.D., Indian Institute of Chemical Technology, Osmania University, India.

Drug Discovery using Organic Synthesis based on Molecular Modeling

We are presently involved in two major areas of research, namely, development of new protein kinase inhibitors for cancer therapy and computationally analyze different aspects of inhibition of cytochrome P450 1A1, 1A2, 2A6, 2B1 and 1B1. We use molecular modeling and computational methods for structure based drug design, quantitative structure activity relationships (QSAR) of biologically active compounds, homology modeling of proteins and molecular dynamic studies. Organic synthetic methods are used to make the designed inhibitors.

When cell life cycle is not regulated, the cell continuously divides out of control leading to the formation of cancer. Nearly all aspects of cell life are controlled by the reversible phosphorylation of proteins which are mainly regulated by protein kinases.  There are 518 human protein kinases. Our group works on the development of small molecule inhibitors for protein kinases (Cyclin Dependent Kinase, CDK; ErbB2 (HER2) kinase; Pim1 kinase, Casein Kinase 1 delta) that can target specific disease conditions such as breast & prostrate cancer, Alzheimer’s, etc. Achieving good potency and selectivity profile for these potential drug candidates is the goal of this project.

1) Department of Defense     
Title: Drug Discovery Partnership for Personalized Breast Cancer Therapy.
Sept. 1, 2011 – Sept. 30, 2015.
Role: co-PI                  Amount: $ 1,284,020

2) Dr. Sridhar was awarded the LCRC Starup award for establishing her research laboratory.
Title: Structure based design of subtpe specific CDK inhibitors.
Sept. 5, 2012 – June 30, 2013.
Role: PI                       Amount: $25,000.

1. Insights on cytochrome P450 enzymes and inhibitors obtained through QSAR studies. Sridhar J, Liu J, Foroozesh M, Stevens CL. Molecules, 2012, 17(8), 9283-305.
2. 7-Ethynylcoumarins: selective inhibitors of human cytochrome P450s 1A1 and 1A2. Liu J, Nguyen TT, Dupart PS, Sridhar J, Zhang X, Zhu N, Stevens CL, Foroozesh M. Chem Res Toxicol., 2012, 25(5),1047-57.
3. Inhibition of Cytochrome P450 Enzymes by Quinones and Anthraquinones. Sridhar J, Foroozesh M, Stevens CL. Chem Res Toxicol., 2012, 25(2), 357-65.
4. QSAR Models of Cytochrome P450 Enzyme 1A2 Inhibitors using CoMFA, CoMSIA and HQSAR. Sridhar J, Foroozesh M, Stevens CL. SAR and QSAR in Environmental Research, 2011, 1-17, published online on October 17, 2011.
5. Effects of 7-O substitutions on estrogenic and anti-estrogenic activities of daidzein analogues in MCF-7 breast cancer cells. Jiang Q, Payton-Stewart F, Elliott S, Driver J, Rhodes LV, Zhang Q, Zheng S, Bhatnagar D, Boue SM, Collins-Burow BM, Sridhar J, Stevens C, McLachlan JA, Wiese TE, Burow ME, Wang G. J Med Chem., 2010, 53(16),6153-63.
6. In Silico Studies of Polyaromatic Hydrocarbon Inhibitors of Cytochrome P450 Enzymes 1A1, 1A2, 2A6, and 2B1. Sridhar J, Jin P, Liu J, Foroozesh M, Stevens CL. Chem. Res. Toxicol., 2010, 23(3), 600-7.
7. Highly potent and specific GSK-3beta inhibitors that block tau phosphorylation and decrease alpha-synuclein protein expression in a cellular model of Parkinson's disease. Kozikowski AP, Gaisina IN, Petukhov PA, Sridhar J, King LT, Blond SY, Duka T, Rusnak M, Sidhu A., ChemMedChem., 2006, 1(2), 256-66.
8. Identification of novel angiogenesis inhibitors. Sridhar J, Akula, N., Sivanesan, D., Narasimhan, M., Rathinavelu, A., Pattabiraman N., Bioorg. Med. Chem. Lett. 2005, 15(18), 4125-9.
9. Binding modes of 6,7 di-substituted 4-anilinoquinoline-3-carbonitriles to EGFR. Akula, N., Bhalla, J., Sridhar J, Pattabiraman, N., Bioorg. Med. Chem. Lett. 2004, 14(13), 3397-400.
10. Mapping the Similarities/Dissimilarities of the active sites of CDK2 and CDK4. Akula, N. Sridhar J, Pattabiraman, N. Hoya Technical Research Bulletin, 2004, 1, 5-7.
11. New Bivalent PKC Ligands Linked By A Carbon Spacer: Enhancement In Binding Affinity; Sridhar J, Wei Z-L, Nowak I, Lewin N. E., Ayres, J. A., Pearce, L. V., Blumberg, P. M., Kozikowski, A. P., J. Med. Chem. 2003, 46(19), 4196-204.

Reviews

1. Selectivity and Potency of Cyclin-Dependent Kinase Inhibitors. Jayalakshmi Sridhar, Akula, N., Pattabiraman, N. Am. Assoc. Pharm. Sci. J., 2006, 8(1),E204-21.
2. Synthesis and isozyme selectivity of small molecule protein kinase C inhibitors: a review of patents. Jayalakshmi Sridhar, Pattabiraman, N. Exp. Opin. Ther. Patents 2005, 15(12), 1691-1701.

Patents

• Vascular Endothelial Receptor Specific Small Molecule Inhibitors. Rathinavelu, A., Pattabiraman, N., Jayalakshmi Sridhar, Dakshanamurthy, S. Publication No: US2007249575 – Date: 2007-10-25
• Inhibitors of Glycogen Synthase Kinase 3. Kozikowski AP, Gaisina IN, Petukhov PA, Jayalakshmi Sridhar, Tueckmantel W. Publication No: WO2007008514 - Date: 2007-01-18.

Book Chapter

• CDK inhibitors as anti-cancer agents: Perspectives for the future. Authors: Jayalakshmi Sridhar, Nagarajan Pattabiraman, Eliot M. Rosen, Richard G. Pestell. Inhibitors of Cyclin-dependent Kinases As Anti-tumor Agents, Edited by Paul James Smith, Eddy W. Yue. CRC Press, 2006, Pg. 389-402.