Contact Us

Mailing address:
Department of Environmental and Molecular Toxicology
Box 7633, NC State University
Raleigh, NC 27695-7633

Shipping address:
Suite 1104, 850 Main Campus Dr.
Raleigh, NC 27606

Phone 919.515.2274
Fax 919.515.7169

Seth W. Kullman, Ph.D.
Assistant Professor
Department of Environmental and Molecular Toxicology

Phone: 919-515-4378
E-mail: swkullma@ncsu.edu

Education

BA,Cellular & Molecular Biology, Chemistry minor, Sonoma State University
PhD, Pharmacology & Toxicology, University of California, Davis
Postdoctoral Fellow, Biochemical & Molecular Toxicology, University of California, Davis

Kullman Curriculum Vitae

 

Research Interests

The Kullman laboratory incorporates molecular, computational, and comparative/functional genomic approaches to examine gene environmental interactions. Studies focus on transcriptional profiling, coupling gene expression with pathology and conducting computational and laboratory-based methods to identify evolutionarily conserved mechanisms of xenobiotic-induced stress response. The goal of this approach is to generate a comprehensive understanding of how genetic and environmental factors interact and influence human and environmental health. Current- efforts in the lab focus on:

  • Activity and Regulation of Drug and Xenobiotic Metabolizing Enzymes
  • Mechanisms of Endocrine Disruption as a Modulatory Factor in Carcinogenesis
  • Toxicogenomics
  • Applied Environmental Toxicology

A common theme in the lab is the role of nuclear receptors (NRs) as targets of xenobiotic stress and toxicity. NR's are ligand-dependent transcription factors that bind to small lipophilic signaling molecules resulting in the control and expression of target genes. They facilitate the cellular response to endogenous and exogenous ligands by coordinating complex transcriptional responses. The nuclear receptor superfamily includes receptors for multiple endobiotics including steroid hormones, retinoids, thyroid hormone, vitamins, prostaglandins, in addition to exogenous ligands including dietary fats, xenobiotics and therapeutic pharmaceuticals. As an emerging theme, nuclear receptors have been shown to serve as endogenous sensors regulating aspects of liver homeostasis. Studies in our laboratories have demonstrated that liver specific NR's including PXR, VDR, PPAR and ER are xenobiotic targets resulting in both genomic and non-genomic transcriptional activation/repression.

Our laboratory uses small aquarium fish as our research model including medaka ( Oryzias latipes ) and zebrafish ( Danio rerio ). Both species of fish are increasingly used as vertebrate model systems in various fields of biology including toxicology and environmental biology. With their suitability for forward and reverse genetic manipulation, ease of handling, and transparent nature of embryos, these models are powerful complementary models for understanding the influence of gene function on disease-related processes in higher vertebrates.

 

 

Sheran Law, Postdoctoral Fellow

Sheran Law is a postdoctoral fellow working in Kullman Laboratory. She is studying the gamma-glutamyl transpeptidase (GGT) genes in medaka. GGTs are transmembrane proteins that cleave gamma-glutamyl amide bonds, mediate the intracellular supply of glutathione and thus play pivotal role in glutathione metabolism. GGT is found in high abundance in kidney tubules where the reabsorption of glutathione takes place. In mammals, they are also expressed in cells of neoplastic foci during liver regeneration. GGT1 gene exhibits a complex promoter structure in the rat genome, where five promoters controlling five functional transcript variants have been reported. Each of the transcripts is expressed in a tissue specific and/or developmental specific pattern. Our interest is to clone and characterize the GGT genes in medaka. Through functional studies of the medaka GGTs, we hope to gain a more cohesive understanding in the roles of GGTs in liver toxicity. Sheran is also establishing a transgenic medaka line for hepatobiliary toxicity evaluation. The promoter IV of the rat GGT1 gene which drives hepatobiliary cell specific expression is linked to the green fluorescent protein (GFP) gene in the transgene construct. Together with the yeast meganuclease I-SceI which enhances chromosome integration, the transgene construct are microinjected into the medaka embryos. All transgenic studies are conducted in the see-through Japanese medaka line where 4 pigment genes are mutated. The transparency of the fish body wall allows non-invasive detection of the GFP signal in vivo. Since medaka are small and easy to handle compared to the larger mammals, we hope to use this transgenic model for high throughput screening of the pharmaceuticals and a wide range of toxicants for their hepatobiliary toxicities.

 

Kullman publications

Selected Publications

Book chapters

  • Hinton, D.E. Segner, H. , Braunbeck, T. and Kullman, S.W., Target Organ Toxicity: The Liver, in Toxicity of Fishes. (Eds) DiGiulo, R and Hinton D.E., CRC Press Boca Raton, Fl. 2007 (In Press)

  • Schlenk, D., James, M., George, S., Gallagher E., Willett, K., van den Hurk, P., Celander, M. and Kullman S. Biotransformation in Fish. in Toxicity of Fishes. (Eds) DiGiulo, R and Hinton D.E., CRC Press Boca Raton, Fl. 2007 (In Press).

  • Lin, S.M, Johnson, K.F., Kullman, S.W, "Bioinformatics Tools", in Genomics and Proteomics in Nutrition , (Eds.) Moustaid-Moussa, N. and Berdanier, C. D., Marcel Dekker, NY, 2004 pp 449-473.

Peer reviewed papers and extended abstracts

  • Hardman RC, Kullman SW and Hinton DE.. 2007. Non Invasive In Vivo Investigation of Hepatobiliary Structure, Function and Xenobiotic Response in STII Medaka (Oryzias latipes): Methodology Overview and Morphometric and Volumetric Analyses. Comp. Hepatol. (In Review)

  • Hardman RC, Kullman SW, Yuen B, and Hinton DE. 2007. Non Invasive High Resolution In Vivo Imaging of Hepatotoxicity in STII Medaka: a -napthylisothiocynate (ANIT) Induced Biliary Toxicity. Aquat. Toxicol. (In Review)

  • Carney MW, Erwin K, Hardman RC, Yuen B, Volz DC, Hinton DC, and Kullman SW. 2007. Differential toxicity of naphthoic acid isomers in medaka (Oryzias latipes) embryos using a 96-well plate format. Marine Pollution Bulletin (In Review)

  • Howarth DL, Law S, Barnes B, Hall JM, Hinton DE , Moore L, Maglich JM, Moore JT and Kullman SW. 2007. Parologus VDRs in Teleosts: Transition of Nuclear Receptor Function. Endocrinology (In Review)

  • Hardman RC, Kullman SW and Hinton DE. 2007. Application of In Vivo Methodologies to Investigate Hepatobiliary Structure, Function and Xenobiotic Response in See-Through Medaka ( Oryzias latipes ). Medaka Journal (In Press)

  • Chen, P. C., E. Rosenfeldt, S. W. Kullman, D. E. Hinton and K. G. Linden. 2007. Biological Assessments of a Mixture of E ndocrine Disruptors at Environmentally Relevant Concentrations in Natural River Water following UV/H 2 O 2 Oxidation. Sci. Total Environ. 376:18-26

  • Rosenfeldt, E., P. J. Chen, S. W. Kullman and K. G. Linden. 2007. Destruction of estrogenic activity in water using UV advanced oxidation. Science of the Total Environment. 377:105-113

  • Kashiwada, S., M. Kameshiro, H. Shiraishi, K. Arizono, S. W. Kullman and David E. Hinton. 2007. Estrogenic modulation of testosterone metabolism in the medaka (Oryzias latipes). Comp. Biochem. Physiol 145:370-8

  • Chen, P.J., S. W. Kullman, D. E. Hinton , and K. G. Linden. 2007. Comparisons of Low- and Medium- Pressure UV lamps on the Removal of Bisphenol A Estrogenic Activity in Water following Direct Photolysis and UV/H 2 O 2 Oxidation Processes. Chemosphere 68:1041-9

  • Hardman RC, Volz DC, Kullman SW and Hinton DE. 2007. An New In Vivo Look at Vertebrate Liver Architecture: 3 Dimensional Reconstructions from Medaka (Oryzias latipes). Anatomical Record 290:770-82.

  • Linden KG, Rosenfeldt EJ and SW. Kullman. 2007. UV/H 2 O 2 degradation of endocrine-disrupting chemicals in water evaluated via toxicity assays. Water Science & Technology. 55:313–319

  • Volz, D. C., D. E. Hinton, J. M. Law, and S. W. Kullman. 2006. Dynamic gene expression changes precede dioxin-induced liver pathogenesis . Toxicol. Sci. 89:524-34

  • Chen, P.J., K.G. Linden, E. J. Rosenfeldt, and S. W. Kullman. 2006 Removal and bio-analytical analysis of Endocrine Disrupting Compounds in water with UV and UV/H 2 O 2 processes. Chemosphere. 65:1094-1102

  • Volz , D.C. , D. C. Bencic, J. M. Law, D. E. Hinton , and S. W. Kullman. 2005. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces organ-specific differential gene expression in Japanese medaka (Oryzias latipes). Toxicol. Sci. 85:572–584

  • Hinton, D. E., S. W. Kullman, D. C. Bencic, R. C. Hardman, P. J. Chen, M. Carney and D.C. Volz. 2005 Resolving mechanisms of toxicity while pursuing ecotoxicological relevance. Marine Pollution Bull. 51: 635-648

  • Kashiwada, S., D. E. Hinton and S. W. Kullman. 2005 Functional characterization of medaka CYP3A38 and CYP3A40 by expression in a recombinant Baculovirus system Comp. Biochem. Physiol 141:338-348

  • Kullman, S. W., S. Kashiwada and D. E. Hinton . 2004. Analysis of medaka cytochrome P4503A homotropic and heterotropic cooperativity. Mar. Environ. Res. 58:469-473

  • Kullman S. W. and D. E. Hinton . 2003. Analysis of medaka CYP3A gene regulation, promoter regulatory regions and cloning of the orphan nuclear receptor PXR. The Bulletin 42:29-31

  • Kullman, S. W., F. Matsumura, and D. E. Hinton . 2003. Estrogen signaling in Trout Liver: Activation of the ras p21/MAP-kinase pathway. Environ. Sci. 10:223-227

  • Liu, Z., S. W. Kullman, D. E. Hinton , and M. Torten. 2003. ras Oncogene mutations in Diethylnitrosamine-induced hepatic tumors in medaka. Mutat. Res. 539:43-53

  • Kullman, S. W. and D. E. Hinton . 2002. Toxicant induced differential gene expression and production of an aquatic gene array. The Bulletin. 41:58-61

  • Arukwe, A., S. W. Kullman, and D. E. Hinton . 2002. Molecular cloning. characterization and expression of the eggshell zona radiata gene in nonylphenol and estrogen-treated Rainbow Trout (Oncorhynchus mykiss). Comp. Biochem. Physiol 132:315-26

  • Kullman, S. W., and D. E. Hinton . 2001. Identification of a second isoform of cytochrome P450 3A from the fresh water teleost medaka (Oryzias latipes): Characterization and ontogeny. Mol. Rep. Dev 58:149-158

  • Arukwe, A., S. W. Kullman, and D. E. Hinton . 2001. Differential biomarker gene and protein expressions in nonylphenol and estradiol-17 b treated juvenile rainbow trout (Oncorhynchus mykiss). Comp. Biochem. Physiol. 129(C):1-10

  • Kullman, S. W., J. T. Hamm, and D. E. Hinton . 2000. Identification and characterization of a cDNA encoding cytochrome P450 3A from the fresh water teleost medaka (Oryzias latipes). Arch. Biochem. Biophys. 380:29-38

  • Kullman, S. W. and F. Matsumura. 1997. Identification of a novel cytochrome P450 gene from the White Rot Fungus Phanerochaete chrysosporium. Appl. Environ. Microbiol. 63:2741-2746

  • Kullman, S. W., and F. Matsumura. 1996. Metabolic pathways utilized by Phanerochaete chrysosporium for degradation of the cyclodiene pesticide endosulfan. Appl. Environ. Microbiol. 62:593-600

  • Kullman, S. W., K. G. Lindenauer, and M. Fuller. Bioremediation Principles: Laboratory Manual. Department of Civil and Environmental Engineering and US Department of Defense, Bioremediation course development for Marie Island Remediation. July. 1995.

  • Lucas, A. D., H. K. M. Bekheit, M. H. Goodrow, A. D. Jones, S. W. Kullman, F. Matsumura, J. N. Seiber, and B. D. Hammock. 1993. Development of antibodies against Hydroxyatrazine and Hydroxysimazine: application to environmental samples. J. Ag. Food Chem. 41:1523-1529.