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
Andrew
D. Wallace, Ph.D.
Assistant Professor
Department of Environmental and Molecular Toxicology
Phone:
919-515-8520
E-mail: andrew_wallace@ncsu.edu
Education
BS,
Biology, Indiana University
MS & PhD,
Toxicology, University of Rochester
Postdoctoral
Fellow,
National Institute of Environmental Health Sciences
Research Interests
The research interests of the laboratory are to define the mechanisms by which toxicants from environmental and occupational exposure impact human health. The laboratory's research is centered on the pregnane X receptor (PXR) or steroid and xenobiotic receptor (SXR), constitutive active/androstane receptor (CAR), glucocorticoid receptor (GR) and other transcription factors those signaling is altered by environmental and occupational exposures. PXR is a transcription factor, found in liver and small intestine, which is activated by binding to endogenous steroids, environmental contaminants, and many prescription and nonprescription drugs. Activation of PXR by xenobiotics (foreign compounds) has been shown to be responsible for the induction of many cytochrome P450s (CYPs) including the main phase I metabolizing enzyme in humans, CYP3A4. PXR has been recognized as a critical mediator in regulating the gene expression of a growing number of key xenobiotic metabolizing and transport proteins and has many other important physiological roles that are only now being elucidated.
The laboratory has initiated an integrated series of studies of the PXR gene and protein at the molecular, cellular, and organism levels. Current research is focused on investigating the role of PXR protein expression in the xenobiotic induction of human CYP3A4 and rodent CYP3As. Much of the research in the laboratory focused on PXR protein concerns defining the environmental toxicants, such as pesticides and phthalates, and chemotherapeutic drugs that bind PXR, the consequences of the PXR activation, as measured by changes in gene expression, and the resulting alterations in metabolism. Future studies of PXR will utilize a transgenic PXR-humanized mouse model and the latest techniques of toxicogenomics to gain a greater understanding of this signal transduction pathway.
In addition, the lab utilizes various human in vitro systems to study the impact of chemical exposures on a number of endpoints including human metabolism, epigenetics, and cytotoxicity.
Xenobiotic activation
of PXR leads to DNA binding and induces the transcription of the xenobiotic
metabolizing protein CYP3A4 and the transport protein MDR.
Selected Publications
- Casabar, R. C., A. D. Wallace, E. Hodgson, and R. L. Rose (2006). Metabolism of endosulfan alpha by human liver microsomes and its utility as a simultaneous in vitro probe for CYP2B6 and CYP3A4. Drug Metab Dispos 34, 1779-85.
- Tompkins, L. M., and A. D. Wallace (2007). Mechanisms of cytochrome P450 induction. J Biochem Mol Toxicol 21, 176-81.
- Wallace, A. D. and S. A. Meyer (2008). Hepatotoxicity. In Molecular and Biochemical Toxicology , Fourth Edition. Eds. Robert Smart and Ernest Hodgson. John Wiley and Sons, Inc. New York .
- Tarnoff, J. B. and A. D.Wallace (2008). Biochemical Mechanisms of Renal Toxicity. In Molecular and Biochemical Toxicology , Fourth Edition. Eds. Robert Smart and Ernest Hodgson. John Wiley and Sons, Inc. New York .
- Das, P.C., T. M. Streit, Y. Cao, R. L. Rose, N. Cherrington, M. K. Ross, A. D. Wallace and E. Hodgson (2008). Pyrethroids: Cytotoxicity and Induction of CYP Isoforms in Human Hepatocytes. Drug Metabol Drug Interact 23: 211-36.
- Tompkins, L. M., T. L. Sit and A. D.Wallace (2008). Unique Transcription Start Sites and Distinct Promoter Regions differentiate the Pregnane X Receptor (PXR) isoforms PXR 1 and PXR 2. Drug Metab Dispos. 36: 923-9
- Cooper, B. W., T. M. Cho, P. M. Thompson and A. D. Wallace (2008). Phthalate Induction of CYP3A4 is Dependent on Glucocorticoid Regulation of PXR Expression. Toxicol Sci 103: 268-77
- Croom, E. L., J. C. Stevens, R. N. Hines, A. D. Wallace and E. Hodgson (2009). Human hepatic CYP2B6 developmental expression: The Impact of Age and Genotype. Biochem Pharmacol 78:184-90
Current Lab Members:
|
Chad Hunter |
Morgan Miller |
Ivey Rice |
Sindhu Chandramoulesswaran
|
Yoonhee Park |
Nneze Eluka |
Former Lab Members:
Chad Hunter, BS in Biological Sciences
Chad received an Office of Undergraduate Research of NC State University 2008-2009 Undergraduate Research Award Grant in support of his research. Chad finished his undergraduate degree at NCSU in 2009 and will be attending Graduate School at East Carolina University in the fall.
Evan Brewer, BS in Biochemistry
Evan finished his undergraduate degree at NCSU in 2009 and completed a Special Problems in Biochemistry undergraduate research project.
Peter Thompson, BS in Biochemistry
Peter completed his undergraduate Honors Thesis and received an Office of Undergraduate Research of NC State University 2007-2008 Research Grant Award in support of his research. Peter finished his undergraduate degree at NCSU in 2008, received an NSF Graduate Student Fellowship, and is now attending Graduate School at the University of North Carolina-Chapel Hill.
Ashley Smith, BS in Biological Sciences
Ashley received an Office of Undergraduate Research of NC State University 2007-2008 Undergraduate Research Award Grant in support of her research. Ashley finished her undergraduate degree at NCSU in 2008 and is now attending Graduate School at the Medical University of South Carolina-Charleston.
Beth Cooper, MS 2007
After After finishing her MS in Toxicology, Beth went on to work for GlaxoSmithKline.
Leslie M. Tompkins, Ph.D. 2007
After finishing her Ph.D. in Toxicology, Leslie went on to a postdoctoral fellowship at the University of Maryland- School of Pharmacy.
Richard C. T. Casabar, MS 2006
After finishing his MS in Toxicology, Richard headed a US Air Force Molecular Toxicology lab.