Fields of Interest
The laboratory is interested in understanding how extrinsic signals influence B lymphocyte growth and survival. We are currently focused on investigating the regulation and function of D-type cyclins in splenic B-2 and peritoneal B-1a cells in response to B-cell antigen receptor engagement. Effort is also directed toward investigating the bioenergetics underlying B-2 lymphocyte survival, specifically identifying signaling and nutrient energy metabolic pathways linked to IL-4 receptors. Specifically, we are using 13C-glucose/13C-glutamine together with 2D-NMR and mass spectrometry to elucidate metabolic pathways that support lymphocyte survival. We are also designing novel carbon nanotube structures in order to efficiently introduce macromolecules (e.g., siRNAs, genes, proteins) into primary B lymphocytes. Additional interests are directed toward developing nanosensors for multiplex detection of disease biomarkers (e.g., cancer and infectious diseases).
Key Representative Publications
Rizal B, Archibald MM, Connolly T, Shepard S, Burns MJ, Chiles TC, Naughton MJ. 2013. A Nanocoax-Based Electrochemical Sensor. Anal Chem. Epub ahead of print.
Blair D, Dufort FJ, Chiles TC. 2012. Protein kinase Cβ is critical for the metabolic switch to glycolysis following B-cell antigen receptor engagement. Biochem J. 448(1):165-9.
Zhao H, Rizal B, McMahon G, Wang H, Dhakal P, Kirkpatrick T, Ren Z, Chiles TC, Naughton MJ, Cai D. 2012. Ultrasensitive chemical detection using a nanocoax sensor. ACS Nano. 6(4):3171-8.
Strelko CL, Lu W, Dufort FJ, Seyfried TN, Chiles TC, Rabinowitz JD, Roberts MF. 2011. Itaconic acid is a mammalian metabolite induced during macrophage activation. J Am Chem Soc. 133(41):16386-9.
Jammallo L, Eidell K, Davis PH, Dufort FJ, Cronin C, Thirugnanam S, Chiles TC, Roos DS, Gubbels MJ. 2011. An insertional trap for conditional gene expression in Toxoplasma gondii: identification of TAF250 as an essential gene. Mol Biochem. Parasitol. 175(2):133-43.
Crane, M.T. and Chiles, T.C. 2011. Why the Liberal Arts Need the Sciences (and Vice Versa). Commentary. The Chronicle of Higher Education. Nov. 13.
Strelko, C.L., Lu, W., Dufort, F.J., Seyfried, T.N., Chiles, T.C., Rabinowitz, J.D., and Roberts, M.F. 2011. Itaconic acid, a polymer building block, is a novel mammalian metabolite induced during macrophage activation. J. Am. Chem. Soc. 133:16386-16389.
Jammallo, L., Eidell, K., Davis, P.H., Dufort, F.J., Cronin, C., Thirugnanam, S., Chiles, T.C., Roos, D.S., and Gubbels, M.J. 2010. An insertional trap for conditional gene expression in Toxoplasma gondii: Identification of TAF250 as an essential gene. Mol. Biochem. Parasitol. 175:133-143.
Gumina, M.R., Xu, C., Chiles, T.C. 2010. Cyclin D3 is dispensable for human diffuse large B-cell lymphoma survival and growth: Evidence for redundancy with cyclin E. Cell Cycle 9(4): 820–828. Epub 2010, Mar. 2.
Yu, Y., Cimeno, A., Lan, Y.C., Rybczynski, J., Wang, D.Z., Paudel, T., Ren, Z.F., Wagner, D.J., Qiu, M.Q., Chiles, T.C., and Cai, D. 2009. Assembly of multi-functional nanocomponents on periodic nanotube array for biosensors. Micro & Nano Letters 4(1): 27–33.
Cai, D., Blair, D., Dufort, F.J., Gumina, M.R., Huang, Z., Hong, G., Wagner, D., Canahan, D., Kempa, K., Ren, Z.F., and Chiles, T.C. 2008. Interaction between carbon nanotubes and mammalian cells: characterization by flow cytometry and application. Nanotechnology 19(34): 1–10.
Wang, Y.K., Chen, W., Blair, D., Pu, M., Xu, Y., Miller, S.J., Redfield, A.G., Chiles, T.C., Roberts, M.F. 2008. Insights into the structural specificity of the cytotoxicity of 3-deoxyphosphatidylinositols. Journal of the American Chemical Society 130(24): 7746–7755. Epub 2008, May 23.
Cai, D., Yu, Y., Lan, Y., Dufort, F.J., Xiong, G., Paudel, T., Ren, Z., Wagner, D.J., and Chiles, T.C. 2007. Glucose sensors made of novel carbon nanotube-gold nanoparticle composites. Biofactors 30(4): 271–277.
Faber, A.C. and Chiles, T.C. 2007. Inhibition of cyclin-dependent kinase-2 induces apoptosis in human diffuse large B-cell lymphomas. Cell Cycle 6(23): 2982–2989.
Dufort, F.J., Bleiman, B., Gumina, M.R., Blair, D., Wagner, D.J., Roberts, M.F., Abu-Amer, Y., and Chiles, T. C. 2007. Interleukin-4-mediated protection of primary B lymphocytes from apoptosis through Stat6-dependent up-regulation of glycolytic metabolism. Cutting Edge: Journal of Immunology 179: 4953–4957.
Chiles, T.C., Mahon, K.P., Potocky, T.B., Blair, D., Roy, M. D., Stewart, K. M., and Kelley, S.O. 2007. Deconvolution of the cellular oxidative stress response with organelle-specific peptide conjugates. Chemistry & Biology 14(8): 923–930.
Doughty, C. A., Bleiman, B. F., Wagner, D. J., Dufort, F. J., Mataraza, J. M., Roberts, M. F., and Chiles, T. C. 2006. Antigen receptor-mediated changes in glucose metabolism in B lymphocytes: role of phosphatidylinositol 3-kinase signaling in the glycolytic control of growth. Blood 107(11): 4458–4465.
Cai, D., Mataraza, J. M., Qin, Z. H., Huang, Z., Huang, J., Chiles, T. C., Carnahan, D., Kempa, K., and Ren, Z. 2005. Highly efficient molecular delivery into mammalian cells using carbon nanotube spearing. Nature Methods 2(6): 449–454.