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Dr. Dianne M. Walters, Ph.D.

Assistant Professor Department of Physiology

Phone: (252) 744-2769
E-mail: waltersd@ecu.edu

Mailing Address:
Brody School of Medicine, 6N-55
600 Moye Blvd.
Greenville, NC 27834

Both genetic and environmental factors contribute to disease etiology, and investigation of gene x environment interactions is critical for understanding disease susceptibility and pathogenesis. Pulmonary fibrosis and chronic bronchitis are examples of complex traits in which genes and environmental agents interact to affect human health. Our laboratory employs unbiased genetic approaches to the discovery of novel genes involved in vanadium pentoxide-induced lung phenotypes in mice.
Vanadium is a transition metal used in a number of industrial applications and is found in ambient particulate matter and emission source particulate pollution. Vanadium pentoxide (V2O5), the most common chemical form of vanadium, has been shown to activate lung fibroblasts and epithelial cells in vitro. In animals, V2O5 exposure induces inflammation, interstitial and peribronchial fibrosis, mucus cell metaplasia (MCM), epithelial cell hyperplasia, and cancer depending on dose/duration of exposure and species/strain of animal. Moreover, acute exposure to vanadium in occupational settings has been associated with decrements in lung function, and occupational bronchitis and asthma in humans. Thus, V2O5 can be used as an environmentally/occupationally relevant murine model of lung disease to identify the genetic basis of susceptibility to interstitial pulmonary fibrosis, inflammation, and MCM.
We have developed a model of V2O5 exposure, and used multiple approaches of genetic linkage analysis to identify quantitative trait loci (QTL) that likely contain susceptibility genes for V2O5-induced pulmonary phenotypes. Future studies will reduce the list of candidate genes for V2O5-induced pulmonary phenotypes using multiple approaches including fine-mapping techniques, sequence analysis, and gene expression profiles. Additionally, the physiological function of candidate genes will be assessed in the V2O5-induced model of pulmonary fibrosis and MCM as well as in other models of fibrotic disease. Longer term goals are to elucidate pathways and mechanisms through which candidate genes function and to identify functional polymorphisms in candidate genes, with the ultimate goal of conducting translational studies to assess the importance of these genes in human populations. This endeavor represents an exciting opportunity to collaborate with a number of basic scientists and medical professionals with access to patient cohorts.

Liu CT, Creasia DA, Walters DM, and Taylor TJ. 1995. Lethality after intratracheal challenge of SEB (Staphylococcal enterotoxin B) in dutch rabbits. Defense Technical Report (AD#299336):1-8.

Palmer WG, Beaman JR, Walters DM, and Creasia, DA. 1997. Bioavailablilty of TNT residues in composts of TNT-contaminated soil. J Toxicol. Envir. Health. 51: 97-108.

Brown RH, Walters DM, Greenberg RS, and Mitzner W. 1999. A method of endotracheal intubation and pulmonary function assessment for repeated studies in mice. J. Appl Physiol. 87(6): 2362-2365.

Walters DM, Wills-Karp M, and Mitzner W. 2000. Assessment of cellular profile and lung function with repeated bronchoalveolar lavage in individual mice. Physiol Genomics 2: 29-36.

Foster WM, Walters DM, Longphre M, Macri K, and Miller LM. 2001. Methodology for the measurement of mucociliary function in the mouse by scintigraphy. J. Appl. Physiol. 90: 1111-1118.

Walters DM, Breysse PN, and Wills-Karp M. 2001. Ambient urban Baltimore particulate-induced airway hyperresponsiveness and inflammation in mice. Am. J. Respir. Crit. Care Med. 164(8): 1438-1443.

Walters DM, Breysse PN, Schofield B, and Wills-Karp M. 2002. Complement factor 3 mediates particulate matter-induced airway hyperresponsiveness. Am. J. Respir. Cell Mol. Biol. 27: 413-418.

Walters DM. 2002. The role of ambient particulate matter in induction of asthma-like parameters in mice. Doctoral Dissertation. The Johns Hopkins Bloomberg School of Public Health.

Wang YZ, Ingram JL, Walters DM, Rice AB, Santos JH, Van Houten B, and Bonner JC. 2003. Vanadium-induced STAT-1 activation in lung myofibroblasts requires H2O2 and P38 MAP kinase. Free Radic Biol Med 35(8):845-55.

Walters DM and Bonner JC. 2005. Signal transduction and cytokine expression in particulate matter (PM)-induced airway remodeling. In Air Pollutants and the Respiratory Tract. 2nd ed. Edited by WM Foster and DL Costa. Vol 204 of series Lung Biology in Health and Disease. Exec editor Claude Lenfant, publisher: Taylor and Francis Group.

Walters DM, Antao-Menezes A, Ingram JL, Rice AB, Nyska A, Tani Y, Kleeberger SR, and Bonner JC. 2005. Susceptibility of signal transducer and activator of transcription-1-deficient mice to pulmonary fibrogenesis. Am J Pathol 167(5):1221-9.

Walters DM, Cho HY, nd Kleeberger SR. 2008. Oxidative stress and antioxidants in the pathogenesis of pulmonary fibrosis: a potential role for NRF2. Antioxid. Redox Signal. 10(2):321-32.

Walters DM, and Kleeberger SR. 2008. Bleomycin-induced pulmonary fibrosis. Current Protocols in Pharmacol. Supp#10;Unit 5.46.

Cho HY, Imani F, Miller-DeGraff L, Walters DM, Melendi GA, Yamamoto M, Polack FP, and Kleeberger SR. 2008. Antiviral activity of Nrf2 in murine airways. Am. J. Respir. Crit. Care Med. In press

Walters DM, Limmon G, Cho HY, Kleeberger SR, and Imani F. PKR protects from bleomycin-induced pulmonary fibrosis. In preparation.

Walters DM, Martin JR, Gladwell W, Bonner JC, and Kleeberger SR. Genetic susceptibility to vanadium pentoxide-induced lung phenotypes: heritability and principal components analysis. In preparation.