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Kullman Laboratory

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

Research Interests

  • Functional role(s) of nuclear and ligand activate receptors as xenobiotic targets.
  • Conservation, variation and evolution of nuclear receptor function.
  • Mechanistic role of aryl hydrocarbon receptor (AhR) in heart, bone and cartilage morphogenesis.
  • Comparative pathogenesis of liver and testicular dysfunction following xenobiotic exposure.
  • Fate, transport and biology of natural steroidal estrogens in the environment.

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.

CURRENT LAB MEMBERS

Dr. Melanie Fraites: NIEHS Postdoctoral fellow-current.  Dr. Fraites earned her PhD in the Department of Physiology and Functional Genomics at the University of Florida College of Medicine. In the Kullman laboratory she is investigating novel mechanisms of AhR action in relation to heart dysmorphogenesis. Here we propose that in addition to the classical AhR/ARNT/DRE mechanism, AhR activation results in rapid non-nuclear, non-classical induction of Cox-2 gene expression. We demonstrate that inflammatory mediators including Cox-2 contribute to the onset and progression of heart dysmorphogenesis in the medaka model. These studies are ongoing are providing a mechanism(s) to demonstrate the role of defined eicosanoid pathways in normal heart development in addition to the relationship between stimulation of inflammation mediators and heart dysmorphogeneis following AhR activation.  

Arnaud Van Wettere: PhD Candidate earned his Doctor in Veterinary Medicine degree from the University of Liege in Belgium. He subsequently completed a residency in avian medicine and obtained his Master of Science degree from the University of Minnesota. After a period as assistant professor of avian medicine at the veterinary school in Munich, Germany, he moved to North Carolina to complete a residency in anatomic pathology at NCSU. Following the residency, he became board certified in veterinary anatomic pathology and joined the Kullman laboratory in 2008 as a graduate student pursuing a PhD in Comparative Biomedical Science. His project investigates the comparative pathogenesis of hepatic fibrosis in the Japanese medaka fish. He is also attempting to establish the location of the hepatic progenitor cell in the fish liver.  Arnaud received a graduate fellowship and was awarded two competitive research awards from the Center for Comparative Medicine & Translational Research, College of Veterinary Medicine North Carolina State University, to conduct his studies. 

Erin Yost: PhD Candidate obtained a BS in Biology from the University of Kentucky in 2003.  Following graduation, she worked for several years as a lab technician with the UK Dept. of Agriculture, and as a field technician with Audubon California.  From 2006-2008, she served Peace Corps volunteer in Madagascar, where she worked with local farmers to develop new crops and improve farming techniques.    She joined Dr. Kullman’s lab in 2008 as a PhD student in Environmental Toxicology. Erin was awarded an EPA Science to Achieve Results (STAR) graduate fellowship in 2010.  Erin’s research examines the fate, transport, and biological activity of natural hormonal estrogens on a swine concentrated animal feeding operation (CAFO).  Swine CAFO waste lagoons have been demonstrated to contain a variety of known contaminants, including appreciable levels of natural estrogens.  These livestock-borne hormones have the potential to enter the environment following the land application of lagoon wastewater to crop fields.  Erin’s research aims to create a “mass balance” for estrogens on a commercial swine CAFO by quantifying the estrogen content of raw swine waste, tracking the transformation of estrogens during holding time in the lagoon, and determining the ultimate fate of these hormones in the environment.  In addition, Erin is using Japanese medaka as a model to study endocrine disruption following exposure to swine CAFO wastewater components, using gene expression as a biological endpoint.

Erin Kollitz: PhD candidate obtained her BA from Bard College in Annandale-on-Hudson, New York in 2005. After graduation, Erin moved to Sarasota Florida and spent three years at Mote Marine Laboratory at the Center for Shark Research and the Center for Ecotoxicology. Erin worked on a variety of projects at Mote, ranging from the effects of environmental estrogens on wild shark populations to the fate and transport of brevetoxins and their impact on human health. She joined the Kullman lab in fall 2008 as PhD student in Environmental Toxicology. Erin is studying the functional diversification of the vitamin D receptor in aquatic vertebrates and is particularly interested in the fate of VDR duplicates that evolved as a result of the teleost specific genome duplication. Outside of the lab, Erin enjoys hiking and backpacking and working on her photography.

 Boknam Lee: PhD candidate is a PhD candidate in Environmental Science and Policy, at Duke University. She received her BS in Environmental Science and Engineering at Hankuk University of Foreign Studies, Seoul, South Korea and a MS in Cvil and Environmental Engineering  from Utah State University. Boknam’s PhD dissertation addresses Bayesian Network Model for Fate and Effects of Hormones in Waste from Swine Concentrated Animal Feeding Operations (CAFOs): Endocrine Disruptors. This project is part of an on going EPA study to investigate the fate and transport of natural steroidal hormones from CAFOs. Boknam is generating a comprehensive model that takes into account building a total estrogen budget to characterize the behavior of estrogens with respect to the physical, chemical, and biological factors that influencing fate, transport and ecological impacts on aquatic organisms. Models have been developed to address (1) characterize the fate, transport of natural estrogens from each swine facility as a function of reproductive phase to the environment, (2) identify the physical, chemical, and biological parameters, influencing the distribution and fate of estrogen compounds throughout each facility system, (3) identify operational procedures that could be modified to reduce estrogen output, (4) predict risks of estrogen to the aquatic ecosystem as a result of estrogen runoff from spray fields, (5) investigate new Best Management Practices (BMPs) to mitigate estrogen fluxes.

Crystal Lee Pow: PhD student received her BS in Biological Sciences and minors of Chemistry and Environmental Science from Carnegie Mellon University in Pittsburgh, PA in the spring of 2010. Crystal has had a wide range of research experiences. Her first undergrad summer was spent in a molecular biology lab working on various projects. The next summer Crystal worked at the Smithsonian Environmental Research Center for a summer, where she collected and analyzed water samples along transects of a brackish marsh on the western Chesapeake Bay. The bulk of her research was spent characterizing dye activating single chain variable fragment antibody clones, for two years in a joint project with a molecular biology lab and an organic chemistry lab. Crystal joined the Kullman Lab in 2011 as a Ph.D student in Toxicology with a concentration in Environmental Toxicology and is a College of Agriculture and Life Sciences (CALS) Deans Graduate Research Assistantship recipient. Crystal’s research project is to understand the impact of Endocrine Disrupting Compounds (EDCs) on North Carolina fisheries.  Studies have demonstrated that exposure to estrogenic compounds can lead to the feminization of male fish and in a recent nationwide survey, NC’s Pee Dee River was implicated for having the highest rate of intersex largemouth bass (Micropterus salmoides). In a joint project with the Fisheries Ecology and Aquatic Science (FEAS) lab (http://www.ncsu.edu/project/fish-lab/) of NC State, Crystal’s job is to do a statewide assessment of intersex fish and the presence of EDCs in NC.

Gwijun Kwon: Research Technician received her BS and MS from the department of horticulture at Seoul National University. She worked as a research assistant in plant molecular biology at the University of Florida and UCSD.  She and her family moved to Raleigh in 2007 from California. She has been working in the lab of Dr. Kullman as a research assistant from 2009.  Her research focuses on role of nuclear receptors LXR and FXR in production of nonalcoholic fatty liver disease in medaka.

PREVIOUS LAB MEMBERS

Dr. Wu Dong: Postdoctoral researcher 2009-2011. Dr Dongs project focused on the molecular pathogenesis of bone and cartilage development/formation in medaka following TCDD exposure. Our laboratory and others have recently demonstrated that strong AhR ligands disrupt craniofacial and axial cartilage and bone development in zebrafish and medaka. Our laboratory has identified a novel hypural cartilage phenotype in the medaka that serves as a prototypic focus of cartilage dysmorphogenesis in these species. Using histological and molecular methods we are developing a working hypothesis that TCDD impacts mesenchymal stem cell differentiation. ­ Dr. Dong is currently at Duke University  dongwu2002@hotmail.com

Dr. Sheran Law: Post doctoral researcher 2006-2009. Sheran Law was a postdoctoral fellow in Kullman Laboratory from 2006-2009. Her project focused on expression and role of of gamma-glutamyl transpeptidase (GGT) genes in medaka tumerogenesis Sheran also developed a transgenic GGT line in medaka as a reporter to assess liver toxicity of cancer therapeutics and screening of pharmaceuticals for hepatobiliary toxicy. While in the Kullman Laboratory Dr. Law received a R.J. Reynolds Post doctoral Fellowship.  Dr Law is currently a NIH: Postdoctoral Fellow at the Eunice Kennedy Shriver National Institute of Child Health and Development, Laboratory of Molecular Genetics, Section on Vertebrate Development with Dr. Thomas D. Sargent. sheranlaw@yahoo.com

Dr. David Bencic Post doctoral researcher 2002-2004. Dr. Bencic studied the differential gene expression of nuclear receptor agonists with a focus on PPARa in medaka. Dr. Bencic is currently a Scientist with the Environmental Protection Agency

Dr. Shosaku Kashiwada Post doctoral researcher 2001-2003. Dr Kashiwata investigated the role of cytochrome 3A activation, repression and cooperativaty following endocrine disruptor exposure. Dr Kashiwata is currently a full Professor within the Department of Life Sciences, at Toyo University. kashiwada@toyo.jp

Hilary Miller, (PhD) completed her PhD in 2011 with Dr’s Kullman and Hinton. Her dissertation investigated the role of estrogen regulated gene expression and nongenomic signaling in spermatogenesis of medakafish (Oryzias Latipes). hilary.miller@duke.edu

Deanna Howarth (PhD) investigated the role of farnesoid X receptor (FXR) in hepatobilary toxicity of aquatic organisms as her PhD topic with Dr’s Kullman and Hinton from 2004-2009. Deanna received a EPA Science to Achieve Results (EPA STAR) fellowship for his doctoral studies. She is currently a Postdoctoral Research Associate in Department of Medicine, Mount Sinai School of Medicine. deannahowarth@gmail.co

David Volz (PhD) conducted his PhD studies on AH receptor signaling and toxic liver injury in medaka fish with Dr’s. Kullman and Hinton from 2003-2006.  Dr. Volz received a EPA Science to Achieve Results (EPA STAR) fellowship for his doctoral studies. He is currently an Assistant professor in the Department of Environmental Health Sciences at University of South Carolina. volz@mailbox.sc.edu

Pei-Jen Chen (PhD) completed her PhD. In 2005 on Removal of Estrogenic Activity of Endocrine Disrupting Compounds in Water With UV and UV/H2O2 Advanced Oxidation Processes, Department of Civil and Environmental Engineering with Dr’s Kullman and Linden (2001-2005). She is currently an Assistant Professor, Department of Agricultural Chemistry, National Taiwan University. chenpj@ntu.edu.tw

Michael Carney (MS) completed a Masters in Environmental Management on the differential developmental toxicity of naphthoic acid isomers in medaka (Oryzias latipes) embryos in 2005. He is currently a research consultant with Stratus Consulting Inc. aquaticare@gmail.com

Dhyanseh Doshi (MS) completed a Masters in Environmental Management investigating endocrine effects of swine CAFO estrogens in 2007. He is currently employed with ICF Consulting Group Holdings. doshi.dhyanesh@gmail.com

LINKS

Society of Toxicology:http://www.toxicology.org

Society of Environmental: Toxicology and Chemistry:   http://www.setac.org

Endocrine Society: www.endo-society.org

Medaka Home Page:  http://biol1.bio.nagoya-u.ac.jp:8000/

Medaka National Biological Resources Project:  http://www.shigen.nig.ac.jp/medaka

Other Medaka resources: Medaka resources