Physicians

Division Chief, Pulmonary and Sleep Medicine

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 physician (or a member of their immediate family) has a working relationship (i.e. consulting, research, and/or educational services) with the companies listed below. These relations have been reported to the health system leadership and, when appropriate, management plans are in place to address potential conflicts.

• Shire Pharmaceuticals

Representative Publications
Rose MC, Voynow JA. Respiratory tract mucin genes and mucin glycoproteins in health and disease. Physiol Rev. 2006 Jan;86(1):245-78. (2006) Abstract

Voynow JA, Gendler SJ, Rose MC. Regulation of mucin genes in chronic inflammatory airway diseases. Am J Respir Cell Mol Biol. 2006 Jun;34(6):661-5. (2006) Abstract

Zheng S, Kenan DJ, Fischer BM, Voynow JA. Neutrophil Elastase Increases MUC5AC Mucin mRNA Expression via Post-Transcriptional Regulation. Proc Am Thorac Soc. 2006 Aug;3(6):543b-544. (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. FASEB J. 2005 Aug;19(10):1374-6. (2005) Abstract

Voynow JA, Fischer BM, Roberts BC, Proia AD. Basal-like cells constitute the proliferating cell population in cystic fibrosis airways. Am J Respir Crit Care Med. 2005 Oct 15;172(8):1013-8. (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. Pediatr Pulmonol. 2004 Dec;38(6):456-64. (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. Am J Physiol Lung Cell Mol Physiol. 2004 Dec;287(6):L1293-302. (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. Am J Physiol Lung Cell Mol Physiol. 2003 Apr;284(4):L671-9. (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 Radic Biol Med. 2003 Nov 1;35(9):1158-67. (2003) Abstract

Fischer BM, Voynow JA. Neutrophil elastase induces MUC5AC gene expression in airway epithelium via a pathway involving reactive oxygen species. Am J Respir Cell Mol Biol. 2002 Apr;26(4):447-52. (2002) Abstract

Voynow JA, Schanberg L, Sporn T, Kredich D. Pulmonary complications associated with Kawasaki disease. J Pediatr. 2002 Jun;140(6):786-7. (2002) Abstract

Voynow JA. What does mucin have to do with lung disease? Paediatr Respir Rev. 2002 Jun;3(2):98-103. (2002) Abstract

Rose MC, Nickola TJ, Voynow JA. Airway mucus obstruction: mucin glycoproteins, MUC gene regulation and goblet cell hyperplasia. Am J Respir Cell Mol Biol. 2001 Nov;25(5):533-7. (2001) Abstract

Berger JT, Voynow JA, Peters KW, Rose MC. Respiratory carcinoma cell lines. MUC genes and glycoconjugates. Am J Respir Cell Mol Biol. 1999 Mar;20(3):500-10. (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. Am J Respir Cell Mol Biol. 1999 Mar;20(3):413-22. (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. Am J Physiol. 1999 May;276(5 Pt 1):L835-43. (1999) Abstract

Adler KB, Fischer BM, Martin LD, Voynow JA (1998) Effects of inflammatory mediators and drugs on mucus secretion and mucociliary function. Res. Immunol. 149:245-248. (1998)

Giuntoli RL 2nd, Rodriguez GC, Whitaker RS, Dodge R, Voynow JA. Mucin gene expression in ovarian cancers. Cancer Res. 1998 Dec 1;58(23):5546-50. (1998) Abstract

Martin LD, Krunkosky TM, Voynow JA, Adler KB (1998) Oxidant-regulated gene expression in inflammatory lung disease, in Acute Respiratory Distress Syndrome: Cellular and Molecular Mechanisms and Clinical Management, Matalon, S. and J.I. Sznajder, Eds., Plenum Press., NY, pp. 187-195. (1998)

Martin LD, Krunkosky TM, Voynow JA, Adler KB. The role of reactive oxygen and nitrogen species in airway epithelial gene expression. Environ Health Perspect. 1998 Oct;106 Suppl 5:1197-203. (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. 1998;176(5):345-54. (1998) Abstract

Voynow JA, Rose MC. Quantitation of mucin mRNA in respiratory and intestinal epithelial cells. Am J Respir Cell Mol Biol. 1994 Dec;11(6):742-50. (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. J Biol Chem. 1991 Nov 15;266(32):21572-7. (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. Anal Biochem. 1988 Feb 1;168(2):367-73. (1988) Abstract

Voynow JA, Charney EB. Fibrodysplasia ossificans progressiva presenting as osteomyelitis-like syndrome. Clin Pediatr (Phila). 1986 Jul;25(7):373-5. (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 Feb 2;21(3):491-7. (1982) Abstract