Physicians

Director, Duke Center for Pediatric Lung Disease

Departments / Divisions

• Pediatrics / Pediatrics-Pulmonary and Sleep Med
• Cell Biology

Address
DUMC 102360
Durham, NC 27710

Appointment Telephone
919-681-3364

Office Telephone
919-684-3364

Fax Telephone
919-684-2292

Training

• MD, University of Pennsylvania School of Medicine, 1982

Residency

• Pediatrics, Children's Hospital Philadelphia (Pennsylvania), 1982-1985

Fellowship

• Pediatric Pulmonology, Children's Hospital Philadelphia (Pennsylvania), 1985-1990

Clinical Interests
Cystic fibrosis, pediatric sleep medicine, pediatric lung disease, flexible fiberoptic laryngoscopy and bronchoscopy, asthma, bronchopulmonary dysplasia, recurrent pneumonia

Research Interests
Cystic Fibrosis (CF) is the most common fatal inherited disease in Caucasians. CF lung disease is characterized by mucus obstruction, and neutrophil-predominant inflammation of the airways. The major macromolecular components of mucus are the mucin glycoproteins. These large heavily glycosylated glycoproteins impart viscoelastic properties to mucus, and under normal conditions, are an important component of lung innate immunity. However, in disease states like CF, increased mucin production and hypersecretion significantly impair pulmonary function and lead to chronic inflammation, infection and eventually lung damage. Our laboratory has been studying the regulation of the major respiratory tract mucins and their functions in the lung.
Our work has focused on the regulation of mucins by neutrophil elastase (NE), a major inflammatory mediator in CF. We have found that NE increases expression of two major respiratory tract mucins, MUC5AC and MUC4, and this effect is mediated by oxidant stress. Furthermore, we found that NE regulates these mucins by a post-transcriptional regulatory mechanism. Our current research endeavors include: 1) determination of MUC mRNA processing within airway epithelial cells and chromatin regulation of MUC expression, 2) analysis of the oxidants/pro-oxidant enzymes regulating MUC expression and 3)evaluation of the mechanisms of airway remodeling following NE exposure.

Another major research focus in our lab is the role of host factors in mediating susceptibility to ozone and inhaled pollutants. We have discovered that the presence of an oxidoreductase, NADPH quinone oxidoreductase 1 (NQO1), is required for ozone-mediated oxidant stress, inflammation and airway hyperresponsiveness. We are currently investigating the NQO1-regulated signaling mechanisms required for ozone-triggered pulmonary toxicity.

Industry Relationships and Collaborations (What's this?)

This faculty member has no reported relationships with industry.

Representative Publications
Voynow, JA; Kummarapurugu, A. Isoprostanes and asthma. Biochimica et Biophysica Acta: international journal of biochemistry and biophysics. 2011;1810:1091-1095. (2011) Abstract

Foster, WM; Adler, KB; Crews, AL; Potts, EN; Fischer, BM; Voynow, JA. MARCKS-related peptide modulates in vivo the secretion of airway Muc5ac. American Journal of Physiology - Lung Cellular and Molecular Physiology. 2010;299:L345-L352. (2010) Abstract

Fischer, BM; Domowicz, DA; Zheng, S; Carter, JL; McElvaney, NG; Taggart, C; Lehmann, JR; Voynow, JA; Ghio, AJ. Neutrophil elastase increases airway epithelial nonheme iron levels. Clinical and Translational Science. 2009;2:333-339. (2009) Abstract

Voynow, JA; Fischer, BM; Zheng, S; Potts, EN; Grover, AR; Jaiswal, AK; Ghio, AJ; Foster, WM. NAD(P)H quinone oxidoreductase 1 is essential for ozone-induced oxidative stress in mice and humans. American Journal of Respiratory Cell and Molecular Biology. 2009;41:107-113. (2009) Abstract

Voynow, JA; Rubin, BK. Mucins, mucus, and sputum. Chest. 2009;135:505-512. (2009) Abstract

Franks, TJ; Colby, TV; Travis, WD; Tuder, RM; Reynolds, HY; Brody, AR; Cardoso, WV; Crystal, RG; Drake, CJ; Engelhardt, J; Frid, M; Herzog, E; Mason, R; Phan, SH; Randell, SH; Rose, MC; Stevens, T; Serge, J; Sunday, ME; Voynow, JA; Weinstein, BM; Whitsett, J; Williams, MC. Resident cellular components of the human lung: current knowledge and goals for research on cell phenotyping and function. Proceedings of the American Thoracic Society. 2008;5:763-766. (2008) Abstract

Voynow, JA; Fischer, BM; Zheng, S. Proteases and cystic fibrosis. The International Journal of Biochemistry and Cell Biology. 2008;40:1238-1245. (2008) Abstract

Fischer, BM; Zheng, S; Fan, R; Voynow, JA. Neutrophil elastase inhibition of cell cycle progression in airway epithelial cells in vitro is mediated by p27kip1. American Journal of Physiology: Lung Cellular and Molecular Physiology. 2007;293:L762-L768. (2007) Abstract

Zheng, S; Byrd, AS; Fischer, BM; Grover, AR; Ghio, AJ; Voynow, JA. Regulation of MUC5AC expression by NAD(P)H:quinone oxidoreductase 1. Free Radical Biology and Medicine. 2007;42:1398-1408. (2007) Abstract

Rose, MC; Voynow, JA. Respiratory tract mucin genes and mucin glycoproteins in health and disease. Physiological Reviews. 2006;86:245-278. (2006) Abstract

Voynow, JA; Gendler, SJ; Rose, MC. Regulation of mucin genes in chronic inflammatory airway diseases. American Journal of Respiratory Cell and Molecular Biology. 2006;34:661-665. (2006) Abstract

Fischer, BM; Cuellar, JG; Byrd, AS; Rice, AB; Bonner, JC; Martin, LD; Voynow, JA. ErbB2 activity is required for airway epithelial repair following neutrophil elastase exposure. The FASEB Journal. 2005;19:1374-1376. (2005) Abstract

Voynow, JA; Fischer, BM; Roberts, BC; Proia, AD. Basal-like cells constitute the proliferating cell population in cystic fibrosis airways. American Journal of Respiratory and Critical Care Medicine. 2005;172:1013-1018. (2005) Abstract

Chitano, P; Voynow, JA; Pozzato, V; Cantillana, V; Burch, LH; Wang, L; Murphy, TM. Ontogenesis of myosin light chain kinase mRNA and protein content in guinea pig tracheal smooth muscle. Pediatric Pulmonology. 2004;38:456-464. (2004) Abstract

Voynow, JA; Fischer, BM; Malarkey, DE; Burch, LH; Wong, T; Longphre, M; Ho, SB; Foster, WM. Neutrophil elastase induces mucus cell metaplasia in mouse lung. American Journal of Physiology: Lung Cellular and Molecular Physiology. 2004;287:L1293-L1302. (2004) Abstract

Fischer, BM; Cuellar, JG; Diehl, ML; deFreytas, AM; Zhang, J; Carraway, KL; Voynow, JA. Neutrophil elastase increases MUC4 expression in normal human bronchial epithelial cells. American Journal of Physiology: Lung Cellular and Molecular Physiology. 2003;284:L671-L679. (2003) Abstract

Krunkosky, TM; Martin, LD; Fischer, BM; Voynow, JA; Adler, KB. Effects of TNFalpha on expression of ICAM-1 in human airway epithelial cells in vitro: oxidant-mediated pathways and transcription factors. Free Radical Biology and Medicine. 2003;35:1158-1167. (2003) Abstract

Fischer, BM; Voynow, JA. Neutrophil elastase induces MUC5AC gene expression in airway epithelium via a pathway involving reactive oxygen species. American Journal of Respiratory Cell and Molecular Biology. 2002;26:447-452. (2002) Abstract

Voynow, JA. What does mucin have to do with lung disease?. Paediatric Respiratory Reviews. 2002;3:98-103. (2002) Abstract

Voynow, JA; Schanberg, L; Sporn, T; Kredich, D. Pulmonary complications associated with Kawasaki disease. Journal of Pediatrics. 2002;140:786-787. (2002) Abstract

Rose, MC; Nickola, TJ; Voynow, JA. Airway mucus obstruction: mucin glycoproteins, MUC gene regulation and goblet cell hyperplasia. American Journal of Respiratory Cell and Molecular Biology. 2001;25:533-537. (2001) Abstract

Berger, JT; Voynow, JA; Peters, KW; Rose, MC. Respiratory carcinoma cell lines. MUC genes and glycoconjugates. American Journal of Respiratory Cell and Molecular Biology. 1999;20:500-510. (1999) Abstract

Fischer, BM; Rochelle, LG; Voynow, JA; Akley, NJ; Adler, KB. Tumor necrosis factor-alpha stimulates mucin secretion and cyclic GMP production by guinea pig tracheal epithelial cells in vitro. American Journal of Respiratory Cell and Molecular Biology. 1999;20:413-422. (1999) Abstract

Voynow, JA; Young, LR; Wang, Y; Horger, T; Rose, MC; Fischer, BM. Neutrophil elastase increases MUC5AC mRNA and protein expression in respiratory epithelial cells. American Journal of Physiology. 1999;276:L835-L843. (1999) Abstract

Giuntoli, RL; Rodriguez, GC; Whitaker, RS; Dodge, R; Voynow, JA. Mucin gene expression in ovarian cancers. Cancer Research. 1998;58:5546-5550. (1998) Abstract

Martin, LD; Krunkosky, TM; Voynow, JA; Adler, KB. The role of reactive oxygen and nitrogen species in airway epithelial gene expression. Environmental Health Perspectives. 1998;106 Suppl 5:1197-1203. (1998) Abstract

Voynow, JA; Selby, DM; Rose, MC. Mucin gene expression (MUC1, MUC2, and MUC5/5AC) in nasal epithelial cells of cystic fibrosis, allergic rhinitis, and normal individuals. Lung: an international journal on lungs, airways and breathing. 1998;176:345-354. (1998) Abstract

Voynow, JA; Rose, MC. Quantitation of mucin mRNA in respiratory and intestinal epithelial cells. American Journal of Respiratory Cell and Molecular Biology. 1994;11:742-750. (1994) Abstract

Voynow, JA; Kaiser, RS; Scanlin, TF; Glick, MC. Purification and characterization of GDP-L-fucose-N-acetyl beta-D-glucosaminide alpha 1----6fucosyltransferase from cultured human skin fibroblasts. Requirement of a specific biantennary oligosaccharide as substrate. Journal of Biological Chemistry. 1991;266:21572-21577. (1991) Abstract

Voynow, JA; Scanlin, TF; Glick, MC. A quantitative method for GDP-L-Fuc:N-acetyl-beta-D-glucosaminide alpha 1----6fucosyltransferase activity with lectin affinity chromatography. Analytical Biochemistry. 1988;168:367-373. (1988) Abstract

Voynow, JA; Charney, EB. Fibrodysplasia ossificans progressiva presenting as osteomyelitis-like syndrome. Clinical Pediatrics. 1986;25:373-375. (1986) Abstract

Scanlin, TF; Voynow, JA; Thomas, EJ; Glick, MC. Glycoproteins in culture medium: a comparison from cystic fibrosis and control skin fibroblasts. Biochemistry. 1982;21:491-497. (1982) Abstract