Biological and environmental oxidants and airway inflammation: Mechanisms of redox signaling



Profile

Albert van der Vliet received his B.S. (1987) and Ph.D. (1991) in Pharmacochemistry at the Free University of Amsterdam, the Netherlands. He worked as a Postdoctororal Researcher at the University of California at Davis in the Department of Internal Medicine, and was appointed as Assistant Research Biochemist at the same Department in 1997, and promoted to Assistant Professor in Residence in 1999 and Associate Professor in Residence in 2001. In 2002, he moved to UVM to take a position as Associate Professor in the Department of Pathology and was promoted to Professor in 2008.

Research Description

Biological and environmental oxidants are believed to contribute to chronic airway diseases such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease. Our research is focused primarily on the respiratory epithelium, the first and major target of inhaled pollutants and itself a source biological oxidants as it expresses nitric oxide synthase (NOS) and NADPH oxidase (NOX/DUOX) enzyme systems. Dysregulated epithelial NOS or NOX/DUOX activation and/or exposure to environmental oxidants may perturb epithelial redox signaling mechanisms and thereby affect epithelial function and airway inflammation. Our general objective is to identify specific cellular targets that are subject to redox regulation and to determine their involvement in epithelial function and airway disease. Within this overall scope, three specific projects are currently ongoing.

[1] Effects of acrolein on airway inflammation: Acrolein is a major environmental pollutant present in cigarette smoke and automobile emissions, etc., and is a highly reactive molecule that reacts with cellular targets involved in redox signaling. Acrolein exposure impacts on inflammatory-immune responses and thereby affects innate host defense and chronic airway inflammation. We are developing proteomic strategies to identify direct cellular targets for acrolein, which include various redox signaling proteins (peroxiredoxins, thioredoxin reductase) as well as redox-sensitive transcription factors (e.g. NF-kB) and caspases, and plan to explore their relative significance for epithelial cell function and inflammatory mediator production and airway inflammation.

[2] Nitric oxide and allergic airway inflammation: Nitric oxide (NO) is produced in the lung during inflammation, and serves important roles in innate host defense and immune regulation, but also regulates epithelial barrier function and repair processes after injury. We are currently exploring the signaling mechanisms of NO focusing on two important transcription factors, NF-kB and HIF-1, that can be regulated by NO through a redox signaling mechanism known as S-nitrosylation. Our goal is to identify the involvement of NO in regulating NF-kB and HIF-1 and its impact on epithelial cell biology in vitro and allergic airway inflammation in vivo.

[3] Dual oxidase in epithelial repair and remodeling: It was recently discovered that airway epithelial cells express an NADPH oxidase homolog, DUOX1, that produces oxidants in response to various stimuli. In addition to a role in innate host defense, DUOX1 activation also participates in epithelial wound repair responses and inflammatory mediator production, by modulating cellular signaling pathways that are linked with epidermal growth factor receptor activation. Although little is known about DUOX1 in lung disease, recent studies suggest altered DUOX expression or activity in allergic airway inflammation and lung cancer. Our goal is to explore the proximal redox signaling mechanisms involved in DUOX1 signaling, and the importance of DUOX1 in airway epithelial repair and remodeling in vivo.

Highlighted Publications

Kasahara, D.I., Poynter, M.E., Othman, Z., Hemenway, D., and van der Vliet, A. Acrolein inhalation suppresses lipopolysaccharide-induced inflammatory cytokine production but does not affect acute airways neutrophilia. J Immunol 2008 Jul 1;181(1):736-45.

Bove, P.F., Hristova, M., Wesley, U.V., Olson, N., Lounsbury, K.M., and van der Vliet, A. Inflammatory levels of nitric oxide inhibit airway epithelial cell migration by inhibition of the kinase ERK1/2 and activation of hypoxia-inducible factor-1 alpha. J Biol Chem 2008 Jun 27;283(26):17919-28. Epub 2008 Apr 18.

Hristova, M., Heuvelmans, S., and van der Vliet, A. GSH-dependent regulation of Fas-mediated caspase-8 activation by acrolein. FEBS Lett 2007 Feb 6;581(3):361-7

Wesley, U.V., Bove, P.F., Hristova, M., McCarthy, S., and van der Vliet, A. Airway epithelial cell migration and wound repair by ATP-mediated activation of dual oxidase 1. J Biol Chem 2007 Feb 2;282(5):3213-20.

Bove, P.F., Wesley, U.V., Greul, A.K., Hristova, M., Dostmann, W.R., and van der Vliet, A. Nitric oxide promotes airway epithelial wound repair through enhanced activation of MMP-9. Am J Respir Cell Mol Biol 2007 Feb;36(2):138-46

View all van der Vliet publications here.

* indicates equal contribution


Albert van der Vliet, Ph.D.

Albert
van der Vliet, Ph.D.

Professor
Department of Pathology

 

802-656-8638
Office: D205 Given
Lab: C264 Given

Lab Members

   Bob Bauer, CMB Student
   Andrew Little, CMB Student

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  • 5/6/2014 12:00 PM - 12:30 PM
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