Faculty

Sharon Lobert

Sharon Lobert, R.N., M.S.N., Ph.D.

University of Mississippi Medical Center
School of Nursing and Department of Biochemistry

E-Mail
Telephone: (601)984-1852

Department of Biochemistry

Graduated in 1989 from Vanderbilt University.

Structure function studies of antimitotic drugs and their interactions with tubulin, protein-protein interactions, drug resistance.

Department of Biochemistry
The long range goal of our research is to understand antimitotic structure-function relationships. Antimitotic agents have been important in cancer chemotherapy for more than 30 years. These drugs interact with tubulin the major protein of mitotic spindles. Mitotic microtubules are dynamic, undergoing assembly and disassembly while aligning chromosomes at the metaphase plate. Antimitotics halt cell division at metaphase by altering microtubule dynamics. Their efficacy in destroying tumors is limited by their toxic profile. Understanding their mechanism of action and the relationship between chemical structure and activity is important for designing new drug analogs, as well as for identifying drugs that can be used in combination at lower, less toxic doses. Often tumors are resistant to antimitotic agents either initially or after repeated drug cycles. We are investigating the tubulin isotype composition of normal and tumor tissues by quantitative realtime PCR, Western blotting and ELISAs. It is possible that tubulin variants in tissues may contribute to antimitotic efficacy and toxicity. Alternatively other proteins that interact with tubulin may be upregulated or downregulated in drug resistant cells and tumors. We are carrying out these studies in both cell culture and animal-derived tumor models.

Department of Biochemistry
Recent Publications

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Lobert, S., Boyd, C.A. and Correia, J.J. Divalent cation and ionic strength effects in vinca alkaloid-induced tubulin self-association. Biophys. J. 72: 416-427, 1997

Lobert, S. Neurotoxicity in Cancer Chemotherapy: Vinca Alkaloids. Critical Care Nurse 17(4): 71-79, 1997

Vulevic, B., Lobert, S. and Correia, J.J. Role of Guanine Nucleotides in the Vinblastine-Induced Self-Association of Tubulin: Effects of GMPCPP and GMPCP. Biochemistry 36: 12828-12835, 1997

Lobert, S., Frankfurter, A. and Correia, J.J. Energetics of Vinca Alkaloid Interactions with Tubulin Isotypes: Implications for Drug Efficacy and Toxicity. Cell Motility and Cytoskeleton 39: 107-121, 1998

Lobert, S., Ingram, J.W., Hill, B.T. and Correia, J.J. A Comparison of Thermodynamic Parameters for Vinorelbine- and Vinflunine-Induced Tubulin Self Association by Sedimentation Velocity. Mol. Pharmacol. 53: 908-915, 1998

Lobert, S., Ingram, J.W., and Correia, J.J. Additivity of Dilantin and Vinblastine Inhibitory Effects on Microtubule Assembly, Cancer Research , 59: 4816-4822, 1999.

Lobert, S. and Correia, J.J. Energetics of Vinca Alkaloid Interactions with Tubulin. Methods in Enzymology , Energetics of Biological Macromolecules, Part C,323: 77-103, 2000.

Lobert, S., Fahy, J., Hill, B.T., Duflos, A., Etievant, C. and Correia, J.J. Vinca Alkaloid-Induced Tubulin Spiral Formation Correlates with Cytotoxicity in the Leukemic L1210 Cell Line. Biochemistry 39: 12053-12062, 2000. [link to PDF]

Lobert, S. Toxicity of Alcohols: Ethanol, Methanol, Polyethylene glycol and Isopropanol. Critical Care Nurse , 60: 41-47, 2000.

Correia, J.J.and Lobert, S. Physiochemical Aspects of Tubulin-Interacting Antimitotic Drugs. Current Pharmaceutical Design, 7(13): 1213-28, 2001. [link to PDF]

Martin, T. and Lobert, S. Chemical Warfare: Nerve Agent Toxicity. Critical Care Nurse , 23(5): 15-20. 2003.

Dozier, J., Hiser, L., Davis, J.A., Thomas, N.D., Tucci, M., Benghuzzi, H.A., Frankfurter, A., Correia, J.J. and Lobert, S. Class II Tubulin Predominates in Normal and Tumor Breast Tissue, Breast Cancer Research, 5: R157-R169, 2003.

Waltman, P.A., Brewer, J.M. and Lobert, S. Thyroid Storm During Pregnancy: A Medical Emergency, Critical Care Nurse, 24 (2), 15-22, 2004.

Mitchell, A., Stevens, B., Mungan, N., Johnson, W., Lobert, S. Analgesic Effects of Sucrose and Pacifier During Eye Examinations for Retinopathy of Prematurity: A Randomized Controlled Trial, Pain Management Nursing, 5(4): 160-168, 2004.

L. Hiser, A. Aggarwal, R. Young, A. Frankfurter, A, Spano, J. J. Correia and S. Lobert. "Correlation of Beta-Tubulin mRNA and Protein Levels in Twelve Human Cancer Cell Lines", Cell Motility & Cytoskeleton, 63: 41-52, 2006. [link to PDF]

J. J. Correia and S. Lobert, (2006) "Molecular Mechanisms of Micotubule Acting Cancer Drugs," in Microtubules in Health and Disease, Humana Press (Ed., Tito Fojo), in press.

S. Lobert and J.J. Correia (2006) "Methods for studying vinca alkaloid interaction with tubulin." Humana Press, (Ed., Jin Zhou), in press.

S. Lobert, J.W. Ingram and J.J. Correia (2007) "The Thermodynamics of Vinca Alkaloid-Induced Tubulin Spiral Formation." Biophys. Chem, Special Issue, Festschrift for Julian Sturtevant,126: 50-58.

Correia, J.J. and Lobert, S. (2008) “Molecular Mechanisms of Microtubule Acting Cancer Drugs”, invited review, in Microtubules in Health and Disease, ed. T. Fojo, Humana Press, pp 21-46.

Aggarwal, A., Kruczynski, A., Frankfurter, A., Correia, J.J., and Lobert, S. (2008) “ Vinca alkaloids demonstrate differential effects on apoptotic pathways in murine leukemia P388 vinorelbine-sensitive and -resistant cell lines”, Investigational New Drugs, 26, 319-330.

Lobert, S. and Puozzo, C. (2008) “Vinflunine Pharmacokinetics Data and Preclinical Model of Toxicity”, Vinflunine Basic Science Summit Proceedings in Seminars in Oncology, 35, Suppl 3, S28-33, invited manuscript.

Jordan, M.A., Horwitz, S.B., Lobert, S., Correia, J.J., and Verdier-Pinard, P. (2008) “ Exploring the mechanisms of action of the novel microtubule inhibitor vinflunine”, Vinflunine Basic Science Summit Proceedings in Seminars in Oncology, 35, Suppl 3, S6-12, invited manuscript.

Cucchiarelli, V.E., Smith, H., Hiser, L., Correia, J.J., Lobert, S. (2008) “Beta-Tubulin isotype classes II and V expression patterns in nonsmall lung tumors, Cell Motility and the Cytoskeleton, 65, 675-685.

Hiser, L., Herrington, B. and Lobert, S. (2008) “Noscapine is synergistic with vincristine and provides neuroprotection of myelin in cell culture. Leukemia and Lymphoma in press.