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David T. Kurtz

Title
InstitutionMedical University of South Carolina
DepartmentCell and Molecular Pharmacology and Experimental Therapeutics
AddressP.O. Box MSC 509
BSB 319F
173 Ashley Ave.
Phone843-792-5844
Fax843-792-2475
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    The Kurtz laboratory studies transcriptional regulation in eukaryotes, and how this regulation determines terminal differentiation of tissues. In addition, the lab studies how these cell growth mechanisms can be disrupted by environmental carcinogens. The Kurtz lab was the first to demonstrate the transcriptional regulation of a eukaryotic gene following gene transfer into tissue culture cells, a technique which is now the most widely used method to study such regulation. Dr. Kurtz was coauthor, along with John Tooze and Nobel Laureate James D. Watson, of the textbook “Recombinant DNA: A Short Course,” published in 1983.

    The transcription factor designated C/EBP alpha has been found to be crucial for the terminal differentiation of liver, lung, granulocytes, and adipocytes, and may also be involved in the development of prostate. The Kurtz lab demonstrated that, in addition to being required for gene expression in these tissues, this transcription factor also serves to prevent cell division, thus maintaining cells in a quiescent state. C/EBP alpha effects this by acting as a potent inhibitor of the family of transcription factors called E2F. The E2F family of factors is required for the cells to enter S phase, where DNA synthesis occurs (see Figure 1). The mutation and/or loss of expression of C/EBP alpha is now recognized as a common occurrence in several types of human cancer, including hepatocellular carcinoma and several types of leukemias. The protein can thus be thought of as a tumor supressor or a “gatekeeper”. The lab is currently examining the mechanisms by which this gene is silenced in human tumors and also studying the mechanisms by which some transformed (cancerous) cells have managed to overcome the block to cell division normally caused by this protein.

    The Kurtz laboratory is also examining the molecular basis of the hepatocarcinogenicity of the environmental chemical trichloroethylene (TCE) and its metabolites, tri- and dichloroacetic acid (TCA and DCA). These compounds cause liver tumors in experimental rodents, although the risk to human health remains to be determined. The lab has found that DCA, when administered to mice and rats, causes a rapid down-regulation of hepatic C/EBP alpha expression, concomitant with the induction of several proto-oncogenes. This results in a transient burst of liver cell division and may result in epigenetic changes leading to tumor formation.

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    Control of Eukaryotic Gene Expression, Cell Division

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    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    1. Chi AC, Appleton K, Henriod JB, Krayer JW, Marlow NM, Bandyopadhyay D, Sigmon RC, Kurtz DT. Differential induction of CYP1A1 and CYP1B1 by benzo[a]pyrene in oral squamous cell carcinoma cell lines and by tobacco smoking in oral mucosa. Oral Oncol. 2009 Nov; 45(11):980-5. PMID: 19576839.
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    2. White-Gilbertson S, Kurtz DT, Voelkel-Johnson C. The role of protein synthesis in cell cycling and cancer. Mol Oncol. 2009 Dec; 3(5-6):402-8. PMID: 19546037.
      View in: PubMed
    3. Walgren JL, Kurtz DT, McMillan JM. Lack of direct mitogenic activity of dichloroacetate and trichloroacetate in cultured rat hepatocytes. Toxicology. 2005 Aug 01; 211(3):220-30. PMID: 15925025.
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    4. Smithwick LA, Quensen JF, Smith A, Kurtz DT, London L, Morris PJ. The inhibition of LPS-induced splenocyte proliferation by ortho-substituted and microbially dechlorinated polychlorinated biphenyls is associated with a decreased expression of cyclin D2. Toxicology. 2004 Nov 01; 204(1):61-74. PMID: 15369849.
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    5. Cleator JH, Ravenell R, Kurtz DT, Hildebrandt JD. A dominant negative Galphas mutant that prevents thyroid-stimulating hormone receptor activation of cAMP production and inositol 1,4,5-trisphosphate turnover: competition by different G proteins for activation by a common receptor. J Biol Chem. 2004 Aug 27; 279(35):36601-7. PMID: 15234971.
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    6. Voelkel-Johnson C, Voeks DJ, Greenberg NM, Barrios R, Maggouta F, Kurtz DT, Schwartz DA, Keller GM, Papenbrock T, Clawson GA, Norris JS. Genomic instability-based transgenic models of prostate cancer. Carcinogenesis. 2000 Aug; 21(8):1623-7. PMID: 10910968.
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    7. Slomiany BA, D'Arigo KL, Kelly MM, Kurtz DT. C/EBPalpha inhibits cell growth via direct repression of E2F-DP-mediated transcription. Mol Cell Biol. 2000 Aug; 20(16):5986-97. PMID: 10913181.
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    8. Walgren JE, Kurtz DT, McMillan JM. Expression of PPAR(alpha) in human hepatocytes and activation by trichloroacetate and dichloroacetate. Res Commun Mol Pathol Pharmacol. 2000 Jul-Aug; 108(1-2):116-32. PMID: 11758968.
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    9. Slomiany BA, Kelly MM, Kurtz DT. Extraction of nuclear proteins with increased DNA binding activity. Biotechniques. 2000 May; 28(5):938-42. PMID: 10818701.
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    10. Walgren JE, Kurtz DT, McMillan JM. The effect of the trichloroethylene metabolites trichloroacetate and dichloroacetate on peroxisome proliferation and DNA synthesis in cultured human hepatocytes. Cell Biol Toxicol. 2000; 16(4):257-73. PMID: 11101007.
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    11. Cleator JH, Mehta ND, Kurtz DT, Hildebrandt JD. The N54 mutant of Galphas has a conditional dominant negative phenotype which suppresses hormone-stimulated but not basal cAMP levels. FEBS Lett. 1999 Jan 25; 443(2):205-8. PMID: 9989606.
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    12. Horney MJ, Shirley DW, Kurtz DT, Rosenzweig SA. Elevated glucose increases mesangial cell sensitivity to insulin-like growth factor I. Am J Physiol. 1998 06; 274(6):F1045-53. PMID: 9841495.
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    13. Everhart JL, Kurtz DT, McMillan JM. Dichloroacetic acid induction of peroxisome proliferation in cultured hepatocytes. J Biochem Mol Toxicol. 1998; 12(6):351-9. PMID: 9736484.
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    14. Morinelli TA, Finley EL, Jaffa AA, Kurtz DT, Ullian ME. Tyrosine phosphorylation of phosphatidylinositol 3-kinase and of the thromboxane A2 (TXA2) receptor by the TXA2 mimetic I-BOP in A7r5 cells. Biochem Pharmacol. 1997 Jun 15; 53(12):1823-32. PMID: 9256157.
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    15. Miller BS, Shankavaram UT, Horney MJ, Gore AC, Kurtz DT, Rosenzweig SA. Activation of cJun NH2-terminal kinase/stress-activated protein kinase by insulin. Biochemistry. 1996 Jul 02; 35(26):8769-75. PMID: 8679641.
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    16. Schwartz DA, Kurtz DT. Sequence requirements for secondary glucocorticoid inducibility of rat alpha 2u globulin genes. Mol Cell Endocrinol. 1996 Jul 01; 120(2):153-9. PMID: 8832575.
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    17. Allan CJ, Higashiura K, Martin M, Morinelli TA, Kurtz DT, Geoffroy O, Meier GP, Gettys TW, Halushka PV. Characterization of the cloned HEL cell thromboxane A2 receptor: evidence that the affinity state can be altered by G alpha 13 and G alpha q. J Pharmacol Exp Ther. 1996 May; 277(2):1132-9. PMID: 8627525.
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    18. Xi D, Kurtz DT, Ramsdell JS. Maitotoxin-elevated cytosolic free calcium in GH4C1 rat pituitary cells nimodipine-sensitive and -insensitive mechanisms. Biochem Pharmacol. 1996 Mar 22; 51(6):759-69. PMID: 8602871.
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    19. Addison WR, Kurtz DT. Identification of nuclear proteins that bind to the glucocorticoid regulatory region of a rat alpha 2u-globulin gene. J Biol Chem. 1989 Dec 25; 264(36):21891-5. PMID: 2480958.
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    20. Oehlenschlager WF, Kurtz DT, Baron DA, Currie MG. Enhanced activity of the cardiac endocrine system during right ventricular hypertrophy. Mol Cell Endocrinol. 1989 Apr; 62(2):243-51. PMID: 2545490.
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    21. Currie MG, Oehlenschlager WF, Kurtz DT. Profound elevation of ventricular and pulmonary atriopeptin in a model of heart failure. Biochem Biophys Res Commun. 1987 Nov 13; 148(3):1158-64. PMID: 2961333.
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    22. MacInnes JI, Nozik ES, Kurtz DT. Tissue-specific expression of the rat alpha 2u globulin gene family. Mol Cell Biol. 1986 Oct; 6(10):3563-7. PMID: 2432391.
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    23. Addison WR, Kurtz DT. Nucleotide sequences required for the regulation of a rat alpha 2u-globulin gene by glucocorticoids. Mol Cell Biol. 1986 Jul; 6(7):2334-46. PMID: 2431290.
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    24. Kurtz DT, McCullough L, Bishop DK, Manos MM. DNA sequences required for hormonal induction of rat alpha 2u-globulin genes. Cold Spring Harb Symp Quant Biol. 1983; 47 Pt 2:985-8. PMID: 6190615.
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    25. Kurtz DT. Hormonal inducibility of rat alpha 2u globulin genes in transfected mouse cells. Nature. 1981 Jun 25; 291(5817):629-31. PMID: 6165894.
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    26. Drickamer K, Kwoh TJ, Kurtz DT. Amino acid sequence of the precursor of rat liver alpha 2 micro-globulin. J Biol Chem. 1981 Apr 25; 256(8):3634-6. PMID: 6163771.
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    27. Kurtz DT, Nicodemus CF. Cloning of alpha 2u globulin cDNA using a high efficiency technique for the cloning of trace messenger RNAs. Gene. 1981 Mar; 13(2):145-52. PMID: 6165648.
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    28. Kurtz DT. Rat alpha 2u globulin is encoded by a multigene family. J Mol Appl Genet. 1981; 1(1):29-38. PMID: 6180115.
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    29. Chan KM, Kurtz DT, Feigelson P. Transcription of the alpha2u-globulin gene in male rat liver nuclei in vitro. Biochemistry. 1978 Jul 25; 17(15):3092-6. PMID: 81070.
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    30. Kurtz DT, Sippel AE, Ansah-Yiadom R, Feigelson P. Effects of sex hormones on the level of the messenger RNA for the rat hepatic protein alpha 2u globulin. J Biol Chem. 1976 Jun 25; 251(12):3594-8. PMID: 58865.
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