Charles K. Singleton, Ph.D.
Chair, Biological Sciences Department
Vanderbilt University Medical Center
Box 1634, Station B
Nashville, TN 37232
Cell-cell and cell-environment signaling during development.
We investigate a variety of regulatory phenomena related to various aspects of development in Dictyostelium. This includes studies on sensory histidine kinases, trans-sensor ammonia transporters, and eIF2-alpha kinases in relation to their role in regulating aspects of multicellular development. The common theme is how communication amoung cells and between cells and their environment is accomplished and implemented to allow coordinated morphological development and cell differentiation. Our studies include the mechamisms underlying the regulation of the timing of development, the choice between alternative developmental pathways, the coordination of differentiation and morphogenesis, and the transition from growth to multicellular development. Our main approaches are genetic, molecular genetic, and biochemical.
- Singleton, CK, Xiong, Y, Kirsten, JH, Pendleton, KP eIF2¿¿ kinases regulate development through the BzpR transcription factor in Dictyostelium discoideum. PLoS One, 7(3), e32500, 2012.
- Bowman, RL, Xiong, Y, Kirsten, JH, Singleton, CK eIF2¿¿ kinases control chalone production in Dictyostelium discoideum. Eukaryot Cell, 10(4), 494-501, 2011.
- Kirsten, JH, Xiong, Y, Davis, CT, Singleton, CK Subcellular localization of ammonium transporters in Dictyostelium discoideum. BMC Cell Biol, 971, 2008.
- Rai, M, Xiong, Y, Singleton, CK Disruption of the ifkA and ifkB genes results in altered cell adhesion, morphological defects and a propensity to form pre-stalk O cells during development of Dictyostelium. Differentiation, 74(9-10), 583-95, 2006.
- Singleton, CK, Kirsten, JH, Dinsmore, CJ Function of ammonium transporter A in the initiation of culmination of development in Dictyostelium discoideum. Eukaryot Cell, 5(7), 991-6, 2006.
- Kirsten, JH, Xiong, Y, Dunbar, AJ, Rai, M, Singleton, CK Ammonium transporter C of Dictyostelium discoideum is required for correct prestalk gene expression and for regulating the choice between slug migration and culmination. Dev Biol, 287(1), 146-56, 2005.
- Peter R. Martin, Charles K. Singleton, and Susanne Hiller-Sturmh?fel "The Role of Thiamine Deficiency in Alcoholic Brain Disease. Alcohol Research & Health.." Alcohol Research & Health, 27134-142, 2004.
- Fang, R, Xiong, Y, Singleton, CK IfkA, a presumptive eIF2 alpha kinase of Dictyostelium, is required for proper timing of aggregation and regulation of mound size. BMC Dev Biol, 33, 2003.
- Follstaedt, SC, Kirsten, JH, Singleton, CK Temporal and spatial expression of ammonium transporter genes during growth and development of Dictyostelium discoideum. Differentiation, 71(9-10), 557-66, 2003.
- Martin, PR, Singleton, CK, Hiller-SturmhÃ¶fel, S The role of thiamine deficiency in alcoholic brain disease. Alcohol Res Health, 27(2), 134-42, 2003.
- Song, Q, Singleton, CK Mitochondria from cultured cells derived from normal and thiamine-responsive megaloblastic anemia individuals efficiently import thiamine diphosphate. BMC Biochem, 38, 2002.
- Singleton, CK, Martin, PR Molecular mechanisms of thiamine utilization. Curr Mol Med, 1(2), 197-207, 2001.
- Singleton, C. K "Transketolase." Encyclopedia of Molecular Medicine, 3224-322, 2001.
- Wang, J. J-L., Hua, Z., Fentress, H. M., and Singleton, C. K "JNK1 is inactivated during thiamine deficiency-induced apoptosis in human neruoblastoma cells." J. Nutri. Biochem., 11208-215, 2000.
- Ragan, P.W., Singleton, C.K., and Martin, P.R "Brain injury associated with chronic alcoholism." CNS Spectrums, 466-87, 1999.
- Pekovich, S. R., Martin, P. R., Poggi, V. and Singleton, C. K "Sensitivity to thiamine deficiency in cultered human cells is dependent on cell type and is enhanced in cells from thiamine- responsive megaloblastic anemia patients." J. Nutri. Biochem, 9215-222, 1998.
- Singleton, CK, Zinda, MJ, Mykytka, B, Yang, P The histidine kinase dhkC regulates the choice between migrating slugs and terminal differentiation in Dictyostelium discoideum. Dev Biol, 203(2), 345-57, 1998.
- Zinda, MJ, Singleton, CK The hybrid histidine kinase dhkB regulates spore germination in Dictyostelium discoideum. Dev Biol, 196(2), 171-83, 1998.
- Pekovich, SR, Martin, PR, Singleton, CK Thiamine deficiency decreases steady-state transketolase and pyruvate dehydrogenase but not alpha-ketoglutarate dehydrogenase mRNA levels in three human cell types. J Nutr, 128(4), 683-7, 1998.
- Wang, JJ, Martin, PR, Singleton, CK A transketolase assembly defect in a Wernicke-Korsakoff syndrome patient. Alcohol Clin Exp Res, 21(4), 576-80, 1997.
- Wang, JJ, Martin, PR, Singleton, CK Aspartate 155 of human transketolase is essential for thiamine diphosphate-magnesium binding, and cofactor binding is required for dimer formation. Biochim Biophys Acta, 1341(2), 165-72, 1997.
- Singleton, CK Identification and characterization of the thiamine transporter gene of Saccharomyces cerevisiae. Gene, 199(1-2), 111-21, 1997.
- Wang, J.-L., Martin, P. R., and Singleton, C. K "Aspartate 155 of human transketolase is essential for thiamine pyrophosphate-magnesium binding, and cofactor binding is required for dimer formation." Biochem. et. Biophys. Acta, 1341165-172, 1996.
- Singleton, CK, Wang, JJ, Shan, L, Martin, PR Conserved residues are functionally distinct within transketolases of different species. Biochemistry, 35(49), 15865-9, 1996.
- Pekovich, SR, Martin, PR, Singleton, CK Thiamine pyrophosphate-requiring enzymes are altered during pyrithiamine-induced thiamine deficiency in cultured human lymphoblasts. J Nutr, 126(7), 1791-8, 1996.
- Martin, PR, McCool, BA, Singleton, CK Molecular genetics of transketolase in the pathogenesis of the Wernicke-Korsakoff syndrome. Metab Brain Dis, 10(1), 45-55, 1995.
- Singleton, CK, Pekovich, SR, McCool, BA, Martin, PR The thiamine-dependent hysteretic behavior of human transketolase: implications for thiamine deficiency. J Nutr, 125(2), 189-94, 1995.
- Ken, R, Singleton, CK Redundant regulatory elements account for the developmental control of a ribosomal protein gene of Dictyostelium discoideum. Differentiation, 55(2), 97-103, 1994.
- Martin, PR, Pekovich, SR, McCool, BA, Whetsell, WO, Singleton, CK Thiamine utilization in the pathogenesis of alcohol-induced brain damage. Alcohol Alcohol Suppl, 2273-9, 1994.
- McCool, B. A., Plonk, S. G., Martin, P. R., and Singleton, C. K "Cloning of human transketolase and comparison of the nucleotide sequence of the coding region in Wernicke-Korsakoff and non-Wernicke-Korsakoff individuals." J. Biol. Chem., 2681397-1404, 1993.
- McCool, BA, Plonk, SG, Martin, PR, Singleton, CK Cloning of human transketolase cDNAs and comparison of the nucleotide sequence of the coding region in Wernicke-Korsakoff and non-Wernicke-Korsakoff individuals. J Biol Chem, 268(2), 1397-404, 1993.
- Martin, P.R., McCool, B.A., and Singleton, C.K "Genetic sensitivity to thiamine deficiency and development of alcoholic organic brain disease." Alcoholism: Clin. & Exp. Res., 1731-37, 1993.
- Martin, PR, McCool, BA, Singleton, CK Genetic sensitivity to thiamine deficiency and development of alcoholic organic brain disease. Alcohol Clin Exp Res, 17(1), 31-7, 1993.
- McPherson, CE, Singleton, CK Nutrient-responsive promoter elements of the V4 gene of Dictyostelium discoideum. J Mol Biol, 232(2), 386-96, 1993.
- McPherson, CE, Singleton, CK V4, a gene required for the transition from growth to development in Dictyostelium discoideum. Dev Biol, 150(2), 231-42, 1992.
- Singleton, CK, Delude, RL, Ken, R, Manning, SS, McPherson, CE Structure, expression, and regulation of members of the developmentally controlled V and H gene classes from Dictyostelium. Dev Genet, 12(1-2), 88-97, 1991.
- Singleton, CK Nucleotide sequence of V1, a ribosomal protein gene from Dictyostelium discoideum. Nucleic Acids Res, 17(19), 7989, 1989.
- Singleton, CK, Manning, SS, Ken, R Primary structure and regulation of vegetative specific genes of Dictyostelium discoideum. Nucleic Acids Res, 17(23), 9679-92, 1989.
- Singleton, CK, Gregoli, PA, Manning, SS, Northington, SJ Characterization of genes which are transiently expressed during the preaggregative phase of development of Dictyostelium discoideum. Dev Biol, 129(1), 140-6, 1988.
- Singleton, CK, McPherson, CE, Manning, SS Deactivation of gene expression upon the onset of development in dictyostelium discoideum. Dev Genet, 9(4-5), 327-35, 1988.
- Singleton, CK, Manning, SS, Feng, Y Effect of protein synthesis inhibition on gene expression during early development of Dictyostelium discoideum. Mol Cell Biol, 8(1), 10-6, 1988.
- Singleton, C.K., Delude, R.L., and McPherson, C.E "Characterization of genes which are deactivated upon the onset of development of Dictyostelium discoideum." Dev. Biol., 119433-441, 1987.
- Singleton, C.K "Left-handed helical DNA in solution." Topics in Nucleic Acids Structure 3, (S. Neidle, ed.).Macmillan Publishers LTD, Houndsmill, UK, 163-192, 1987.
- Singleton, CK pPAV, a promoter analysis vector for Dictyostelium discoideum. Nucleic Acids Res, 15(22), 9610, 1987.
- Singleton, C.K "Structural heterogeneity of duplex DNA." Cell Proliferation: Recent Advances, vol. I (A.L. Boynton and H.L. Leffert, eds.). Academic Press, Inc., New York, NY, 417-447, 1985.
- Singleton, C.K., Kilpatrick, M.W., and Wells, R.D "S1 nuclease recognizes DNA conformational junctions between left-handed helical (dT-dG)n .(dC-dA)n and contiguous right-handed sequences." J.Biol. Chem., 2591963-1967, 1984.
- Singleton, C.K., Klysik, J., and Wells, R.D "Conformational flexibility of junctions between contiguous B and Z DNA in supercoiled plasmids." Proc. Natl. Acad. Sci. USA, 802447-2451, 1983.
- Singleton, C.K "Effects of salts, temperature, and stem length on supercoil induced formation of cruciforms." J. Biol. Chem., 2587661-7668, 1983.
- Singleton, C.K., Klysik, J., Stirdivant, S.M., and Wells, R.D "Left-handed Z-DNA is induced by supercoiling under physiological ionic conditions." Nature, 299312 316, 1982.
- Singleton, C.K. and Wells, R.D "The facile generation of covalently closed, circular DNAs of defined negative superhelical densities." Anal. Biochem., 122253-257, 1982.