Lab Members

Lab Members

Jump to ...
Graduate Students Postdoctoral Fellows Researchers / Staff Principal Investigator

Graduate Students

None

Return to Top

Postdoctoral Fellows

Deepak Gurbani, Ph.D. – Biophysics/Biochemistry

deepak

Education: B.S – Biology, 1999, Kanpur University, India. M.S – Botany, 2001, Kanpur University, India. Ph.D – Biotechnology, 2012, CSIR-Indian Institute of Toxicology Research & Jamia Hamdard University, New Delhi, India.

Research interests: Mechanisms that transform normal cells to cancer cells are complex. I study how small molecules perturb the function of key cellular enzymes. Kinases play a vital role in cellular physiology and normal and abnormal growth. My research includes performing X-ray crystallography, enzymatic and cellular assays to study structure and function of different kinases. I also work in collaboration with medicinal chemists to develop reversible and irreversible inhibitors of kinases involved in different cancers.

Selected publications:

J. Totzke, D. Gurbani*, R. Raphemot, P.F. Hughes, K. Bodoor, D.A. Carlson, D. R. Loiselle, A. K. Bera, L.S. Eibschutz, M.M. Perkins, A.L. Eubanks, P. Campbell, D.A. Fox, K.D. Westover, T.A. Haystead, E.R. Derbyshire. Takinib, an exquisitely selective inhibitor of TAK1, targets pro survival TNFα-dependent signaling, inducing apoptosis in rheumatoid arthritis and breast cancer models. Cell Chemical Biology 24 (2017), 1029–1039.

L. Tan, D. Gurbani*, E.L. Weisberg, D.S. Jones, S. Rao, W.D. Singer, F.M. Bernard, S. Mowafy, A. Jenney, G. Du, A. Nonami, J.D. Griffin, D.A. Lauffenburger, K.D. Westover, P.K. Sorger, N.S. Gray, Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors, Bioorg Med Chem, 25 (2017) 1320-1328.

L. Tan, D. Gurbani*, E.L. Weisberg, J.C. Hunter, L. Li, D.S. Jones, S.B. Ficarro, S. Mowafy, C.P. Tam, S. Rao, G. Du, J.D. Griffin, P.K. Sorger, J.A. Marto, K.D. Westover, N.S. Gray, Structure-guided development of covalent TAK1 inhibitors, Bioorg Med Chem, 25 (2017) 838-846.

L. Tan, T. Nomanbhoy, D. Gurbani, M. Patricelli, J. Hunter, J. Geng, L. Herhaus, J. Zhang, E. Pauls, Y. Ham, H.G. Choi, T. Xie, X. Deng, S.J. Buhrlage, T. Sim, P. Cohen, G. Sapkota, K.D. Westover, N.S. Gray, Discovery of type II inhibitors of TGFbeta-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2), J Med Chem, 58 (2015) 183-196.

J.C. Hunter, D. Gurbani, S.B. Ficarro, M.A. Carrasco, S.M. Lim, H.G. Choi, T. Xie, J.A. Marto, Z. Chen, N.S. Gray, K.D. Westover, In situ selectivity profiling and crystal structure of SML-8-73-1, an active site inhibitor of oncogenic K-Ras G12C, Proc Natl Acad Sci U S A, 111 (2014) 8895-8900.

D. Gurbani, V. Kukshal, J. Laubenthal, A. Kumar, A. Pandey, S. Tripathi, A. Arora, S.K. Jain, R. Ramachandran, D. Anderson, A. Dhawan, Mechanism of inhibition of the ATPase domain of human topoisomerase IIalpha by 1,4-benzoquinone, 1,2-naphthoquinone, 1,4-naphthoquinone, and 9,10-phenanthroquinone, Toxicol Sci, 126 (2012) 372-390. Article on Cover Page, April issue.

*Equal Contribution.

Return to Top

Jia (Jack) Lu, Ph.D. – Biophysics/Biochemistry

Jack Lu

Education: B.S. – Biotechnology, 2003, East China Normal University; PhD – Molecular and Cell Biology, 2012,The University of Texas at Dallas.

Research interests: High resolution protein structures and their functional role in protein-ligand interactions. Drug development for targeting mutations in cancer biology.

Selected publications:

Lu J, Harrison RA, Li L, Zeng M, Gondi S, Scott D, Gray NS, Engen JR, Westover KD. KRAS G12C Drug Development: Discrimination between Switch II Pocket Configurations Using Hydrogen/Deuterium-Exchange Mass Spectrometry. Structure. 2017 Sep 5;25(9):1442-1448

Harrison RA, Lu J, Carrasco M, Hunter J, Manandhar A, Gondi S, Westover KD*, Engen JR*. Structural dynamics in Ras and related proteins upon nucleotide switching. J Mol Biol. 2016 Oct 14.

Zeng M, Lu J, Li L, Feru F, Quan C, Gero TW, Ficarro SB, Xiong Y, Ambrogio C, Paranal RM, Catalano M, Shao J, Wong KK, Marto JA, Fischer ES, Jänne PA, Scott DA, Westover KD*, Gray NS. Potent and Selective Covalent Quinazoline Inhibitors of KRAS G12C. Cell Chem Biol. 2017 Aug 17;24(8):1005-1016.

Xiong, Y, Lu J,  Hunter J,  Li L, Scott D,  Choi HG, Lim SM, Manandhar A, Gondi S,  Sim T, Westover KD*, Gray NS*. Development of covalent guanosine mimetic inhibitors of G12C KRAS. ACS Med Chem Lett. 2016 Nov 30;8(1):61-66. doi: 10.1021/acsmedchemlett.6b00373.

Return to Top

Lianbo Li, Ph.D. – Biophysics/Biochemistry

Lianbo

Education: B.S. – Biotechnology, 2007, Shandong Normal University, China; PhD – Cell Biology, 2014, Peking University, China.

Research interests: Protein structure guided drug discovery with emphasis on the oncogenic protein KRAS.

Selected publications:

Zeng, M., Lu, J., Li, L., Feru, F., Quan, C., Gero, T. W., Ficarro, S. B., Xiong, Y., Ambrogio, C., Paranal, R. M., Catalano, M., Shao, J., Wong, K. K., Marto, J. A., Fischer, E. S., Janne, P. A., Scott, D. A., Westover, K. D., and Gray, N. S. (2017) Potent and Selective Covalent Quinazoline Inhibitors of KRAS G12C. Cell Chem Biol.

Lu, J., Harrison, R. A., Li, L., Zeng, M., Gondi, S., Scott, D., Gray, N. S., Engen, J. R., and Westover, K. D. (2017) KRAS G12C Drug Development: Discrimination between Switch II Pocket Configurations Using Hydrogen/Deuterium-Exchange Mass Spectrometry. Structure.

Xiong, Y., Lu, J., Hunter, J., Li, L., Scott, D., Choi, H. G., Lim, S. M., Manandhar, A., Gondi, S., Sim, T., Westover, K. D., and Gray, N. S. (2017) Covalent Guanosine Mimetic Inhibitors of G12C KRAS. ACS medicinal chemistry letters 8, 61-66.

Montalvo, S. K., Li, L., and Westover, K. D. (2017) Rationale for RAS mutation-tailored therapies. Future Oncol 13, 263-271.

Li, L., Zhang, W., Liu, Q., Gao, Y., Gao, Y., Wang, Y., Wang, D. Z., Li, Z., and Wang, T. (2013) Structural Insights on the bacteriolytic and self-protection mechanism of muramidase effector Tse3 in Pseudomonas aeruginosa. J Biol Chem 288, 30607-30613.

Return to Top

Zhi-Wei (George) Zhou, Ph.D. – Cancer Biology/Biophysics

george

Education: B.S.- Biotechnology and Pharmacology, 2007, Nanchang University, China; Ph.D.- Health Sciences, 2013, RMIT University, Melbourne, Australia

Research interests: Cancer pharmacology and anticancer drug (synthesized and natural compounds) discovery and development, with a specific focus on KRAS.

Selected publications:

He SJ, Shu LP, Zhou ZW, Yang TX, Duan W, Zhang X, He ZX, Zhou SF. Inhibition of Aurora kinases induces apoptosis and autophagy via AURKB/p70S6K/RPL15 axis in human leukemia cells. 2016; Cancer Letters 2016 Sep 6;382(2):215-230.

Li YC, He SM, He ZX, Li M, Yang Y, Pang JX, Zhang X, Chow K, Zhou Q, Duan W, Zhou ZW, Yang T, Huang GH, Liu A, Qiu JX, Liu JP & Zhou SF. Plumbagin induces apoptotic and autophagic cell death through inhibition of the PI3K/Akt/mTOR pathway in human non-small cell lung cancer cells. Cancer Lett 2014 Mar 28;344(2):239-259. 24280585.

Li M, Yang Y, He ZX, Zhou ZW, Yang T, Guo P, Zhang X & Zhou SF. MicroRNA-561 promotes acetaminophen-induced hepatotoxicity in HepG2 cells and primary human hepatocytes through down-regulation of the nuclear receptor co-repressor dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on X chromosome, gene 1 (DAX-1). Drug Metab Dispos 2014 Jan;42(1):44-61. 24104199.

Zhou ZW, Xie XL, Zhou SF & Li CG. Mechanism of reversal of high glucose-induced endothelial nitric oxide synthase uncoupling by tanshinone IIA in human endothelial cell line EA.hy926. Eur J Pharmacol 2012 Dec 15;697(1-3):97-105.

Return to Top

Researchers / Staff

Yan Liu, Ph.D. – Cancer Biology

Yan

Education: B.S. - Biochemistry, 1999, Nankai University, China; Ph.D. – Biochemistry, 2009, Ohio University

Research interests: Cancer Biology, Kinase Inhibitor Development, Molecular Cancer Epidemiology

Selected publications:

Yan Liu, Csaba Laszlo, Yi Liu, Wei Liu, Xiaozhuo Chen, Susan C Evans, Shiyong Wu. (2010) Regulation of G1 Arrest and Apoptosis in Hypoxia by PERK and GCN2-mediated eIF2 Phosphorylation. Neoplasia 12(1): 61–68.

Yan Liu, Pui-Kai Li, Chenglong Li, Jiayuh Lin. (2010) Inhibition of STAT3 Signaling Blocks the Anti-Apoptotic Activity of IL-6 in Human Liver Cancer Cells. Journal of Biological Chemistry 285(35):27429-39.

Yan Liu, James Fuchs, Chenglong Li, Jiayuh Lin. (2010) IL-6, a Risk Factor for Hepatocellular Carcinoma: FLLL32 Inhibits IL-6-Induced STAT3 Phosphorylation in Human Hepatocellular Cancer Cells. Cell Cycle 9(17):3423-7.

Yan Liu, Aiguo Liu, Zhenghu Xu, Wenying Yu, Hong Wang, Chenglong Li, Jiayuh Lin. (2011) XZH-5 Inhibits Constitutive and Interleukin-6-Induced STAT3 Phosphorylation in Human Hepatocellular Carcinoma Cells. Apoptosis 16(5):502-10.

Yan Liu, Aiguo Liu, Huameng Li, Chenglong Li, Jiayuh Lin. (2011) Celecoxib Inhibits Constitutive and Interleukin-6-Induced STAT3 Phosphorylation in Human Hepatocellular Carcinoma Cells. Cancer Prevention Research 4(8):1296-305.

Yan Liu, Oriana E. Hawkins, Yingjun Su, Anna Vilgelm, Tammy Sobolik-Delmaire, Yee-Mon Thu, Sara Kantrow, Ryan C. Splittgerber, Sara Short, Katayoun I. Amiri, Jeffery A. Ecsedy, Jeffery A. Sosman, Mark C. Kelley, Ann Richmond. (2013) Targeting Aurora Kinases Limits Tumor Growth through DNA Damage Mediated Senescence and Blockade of NF-κB Impairs this Drug Induced Senescence. EMBO Molecular Medicine 5(1): 1946-66.

Yan Liu, Qiuyin Cai, Ping-Ping Bao, Yinghao Su, Hui Cai, Jie Wu, Fei Ye, Xingyi Guo, Wei Zheng, Ying Zheng, and Xiao-Ou Shu. (2015) Tumor tissue microRNA expression in association with triple-negative breast cancer outcomes. Breast Cancer Research and Treatment 152 (1): 183-191

Yan Liu, Oriana E Hawkins, Anna E Vilgelm, Jeff S Pawlikowski, Jeffrey A Ecsedy, Jeffrey Alan Sosman, Mark C Kelley, Ann Richmond. (2015) Combining an Aurora Kinase Inhibitor and a Death Receptor Ligand/Agonist Antibody Triggers Apoptosis in Melanoma Cells and Prevents Tumor Growth in Preclinical Mouse Models. Clinical Cancer Research Online First July 7, 2015; doi: 10.1158/1078-0432

Yan Liu , Michelle Baglia , Ying Zheng , William Blot , Ping-Ping Bao , Hui Cai , Sarah Nechuta , Wei Zheng , Qiuyin Cai, and Xiao-Ou Shu. (2015) ALDH1A1 mRNA expression in Association with Prognosis of Triple-Negative Breast Cancer. Oncotarget Online First October 8, 2015; doi: 10.18632/oncotarget.6023

Harshbarger, W., Gondi, S., Ficarro, S.B., Hunter, J., Udayakumar, D., Gurbani, D., Singer, W.D., Liu, Y., Li, L., Marto, J.A., and Westover, K.D.; Structural and Biochemical Analyses Reveal the Mechanism of Glutathione-S-Transferase Pi 1 Inhibition by the Anti-cancer Compound Piperlongumine; J. Biol. Chem. 292: 112-120 (2017).

Return to Top

Sudershan Gondi, Ph.D. – Chemistry

Sudershan

Education:  Ph.D. - Chemistry, 1997, Osmania University

Research interests: Medicinal chemistry, polymer chemistry and protein chemistry

Selected publications:

Xiong Y, Lu J, Hunter J, Li L, Scott D, Choi HG, Lim SM, Manandhar A, Gondi S, Sim S, Westover KD, & Gray NS. Development of covalent guanosine mimetic inhibitors of G12C KRAS. ACS Med Chem Letters. 2017, 8(1), 61-66. http://dx.doi.org/10.1021/acsmedchemlett.6b00373 

Harshbarger W, Gondi S, Ficarro SB, Hunter J, Udayakumar D, Gurbani D, Singer W, Liu Y, Li L,. Marto JA, Westover KD. Structural and Biochemical Analyses Reveal the Mechanism of Glutathione S-Transferase Pi 1 Inhibition by the Anti-cancer Compound Piperlongumine. JBC, 2017, 292(1), 112-120. http://dx.doi.org/10.1074/jbc.M116.750299 

De P, Li M, Gondi SR, Sumerlin BS. Temperature-Regulated Activity of Responsive Polymer-Protein Conjugates Prepared by Grafting-from via RAFT Polymerization. JACS, 2008, 130(34), 11288-11289. http://dx.doi.org/10.1021/ja804495v  

Gondi SR, Vogt AP, Sumerlin BS. “Versatile Pathway to Functional Telechelics via RAFT Polymerization and Click Chemistry” Macromolecules, 2007, 40(3), 474-481. http://dx.doi.org/10.1021/ma061959v

Gondi SR Son DY. Cholane Derivatives with Potential Ligating Groups at the 3 and 24-Positions. Synthetic Com., 2006, 36(10), 1317-1331. http://dx.doi.org/10.1080/00397910500521803 

Return to Top

William Singer, Ph.D. – Biochemistry

bill

Education: B.S. - Chemistry, 1986, Washburn University; Ph.D. – Biochemistry, 1991, University of Kansas

Research interests: Interaction of chemotherapeutic agents with oncoproteins. Mechanistic studies of cellular signal transduction.

Selected publications:

Tan, L., Gurbani, D., Weisberg, E.L., Jones, D.S., Rao, S., Singer, W.D., Bernard, F.M., Mowafy, S., Jenney, A., Du, G., Nonami, A., Griffin, J.D., Lauffenburger, D.A., Westover, K.D., Sorger, P.K., and Gray, N.S.; Studies of TAK1-centered Polypharmacology With Novel Covalent TAK1 Inhibitors; Bioorg. Med. Chem. 25: 1320-1328 (2017).

Harshbarger, W., Gondi, S., Ficarro, S.B., Hunter, J., Udayakumar, D., Gurbani, D., Singer, W.D., Liu, Y., Li, L., Marto, J.A., and Westover, K.D.; Structural and Biochemical Analyses Reveal the Mechanism of Glutathione-S-Transferase Pi 1 Inhibition by the Anti-cancer Compound Piperlongumine; J. Biol. Chem. 292: 112-120 (2017).

Singer, W.D., Osimiri, L.C., and Friedberg, E.C.; Increased Dietary Cholesterol Intake Stimulates Mutangenesis of DNA in Polymerase Kappa-deficient Mice; DNA Repair 12: 817-823 (2013).

Chen, Z., Singer, W.D., Sternweis, P.C., and Sprang, S.R.; Structure of the p115 RhoGEF rgRGS Domain-Ga13/i1 Chimera Complex Suggests Convergent Evolution of a GTPase Activator; Nat. Struct. Mol. Biol. 12: 191-197 (2005)

Kozasa, T., Jiang, X., Hart, M.J., Sternweis, P.M., Singer, W.D., Gilman, A.G., Bollag, G., and Sternweis, P.C.; p115 RhoGEF, a GTPase Activating Protein for Ga12 and Ga13; Science 280: 2109-2111 (1998).

Hart, M.J.*, Jiang, X.* (*co-first authors), Kozasa, T., Roscoe, W., Singer, W.D., Gilman, A.G., Sternweis, P.C., and Bollag, G.; Direct Stimulation of the Guanine Nucleotide Exchange Activity of p115 RhoGEF by Ga13; Science 280: 2112-2114 (1998).

Singer, W.D., Brown, H.A., and Sternweis, P.C.; Regulation of Eukaryotic Phosphatidylinositol-specific Phospholipase C and Phospholipase D.;  Annu. Rev. Biochem. 66: 475-509 (1997).

Singer, W.D., Brown, H.A., Jiang, X., and Sternweis, P.C.; Regulation of Phospholipase D by Protein Kinase C is Synergistic with ADP-ribosylation Factor and Independent of Protein Kinase Activity; J. Biol. Chem. 271: 4504-4510 (1996).

Singer, W.D. and Himes, R.H.; Cellular Uptake and Tubulin Binding Properties of Four Vinca Alkaloids; Biochem. Pharmacol. 43: 545-551 (1992).

Return to Top

Xingxiao (Shelly) Li, M.S.– Cancer Biology

Shelly

Education: B.S. – Biotechnology, 2007, Nanchung University, China ; M.S. – Cancer Biology, 2010, Guangdong Cardiovascular Institute, China

Research interests: Development of cellular and biological techniques, including, but not limited to culturing noncancerous and cancerous cell lines and molecular biology.

Return to Top