Current Faculty

David Kurtz, PhD

Kurtz PictureProfessor

Education
1978           Ph.D.,
Columbia University

Contact Info
kurtzdt@musc.edu
Tel: 843-792-5844
Fax: 843-792-2475
Office: BSB 319F

Research Interests

Control of Eukaryotic Gene Expression and Cell Division

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.

Recent Publications | Additional Publications


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. Epub 2009 Jul 2. PubMed PMID: 19576839; PubMed Central PMCID: PMC2764788.


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. Epub 2009 Jun 11. Review. PubMed PMID: 19546037; PubMed Central PMCID: PMC2784195.


3: Walgren JL, Kurtz DT, McMillan JM. Lack of direct mitogenic activity of dichloroacetate and trichloroacetate in cultured rat hepatocytes. Toxicology. 2005 Aug 1;211(3):220-30. Epub 2005 Apr 21. PubMed PMID: 15925025.


4: Smithwick LA, Quensen JF 3rd, 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 1;204(1):61-74. PubMed PMID: 15369849.


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. Epub 2004 Jul 2. PubMed PMID: 15234971.

 
 
 

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