Phyllis Armelle Dennery, M.D.
Phyllis Armelle Dennery, M.D.
Professor of Pediatrics
Department: Pediatrics
Graduate Group Affiliations
Contact information
Division of Neonatology
34th and Civic Center Blvd
Philadelphia, PA 19104
34th and Civic Center Blvd
Philadelphia, PA 19104
Office: (215) 590-1653
Fax: 215-267-4632
Lab: 267-426-5694
Fax: 215-267-4632
Lab: 267-426-5694
Email:
dennery@email.chop.edu
dennery@email.chop.edu
Publications
Education:
BSc (Biology-Genetics)
McGill University, 1980.
MD
Howard University, 1984.
Permanent linkBSc (Biology-Genetics)
McGill University, 1980.
MD
Howard University, 1984.
Description of Research Expertise
Research InterestsRole and regulation of heme oxygenase in the neonatal lung.
Developmental differences in response to oxidative stress.
Key words: heme oxygenase, oxidative stress, neonatal, lung, gene regulation, transcription factor, circadian.
Description of Research
Neonates are relatively less susceptible to oxidative stress but suffer long term consequences including chronic lung disease. My laboratory investigates the role and regulation of heme oxygenase-1 (HO-1) in neonatal lung antioxidant defenses. We have shown that over-expression of HO-1 is cytoprotective however, beyond a certain threshold in the lung, there are detrimental effects associated with HO-1. This may be related to other non-enzymatic functions of the HO-1 protein. We have shown that HO-1 protein, devoid of activity can alter cellular signaling and migrate to the nuclear compartment. This mechanism involves a proteolytic cleavage at the C-terminus of the protein. We are currently defining the role of this cleaved protein as a modulator of DNA repair as it binds to various DNA repair proteins to modulate their activity.
We are particularly focusing on the effects of HO-1 in postnatal lung development using murine models with disruption of HO-1 or transgenics over-expressing the HO-1 15 kB promoter drivng the expression of luciferase. Due to the availability of an In vitro imaging system, HO-1 gene expression can be monitored in vivo in real time. This technology along with standard molecular, proteinomic, genomic and histological techniques allows us to answer the questions relating to the role of HO-1 in the developing lung. Other interests are in the role of transcription factors including NF-kB and C-EBPx for neonatal lungs oxidative susceptibility. A recent project is evaluating the circadian rhythm gene Rev-erbx and its role in lung function in response to oxidative stress and its regulation by NF-kB.
Rotation Projects
1. Define specific pathways for HO-1 DNA repair protein interactions
2. Epigenetic regulation of HO-1 gene expression
3. Hyperoxia regulation of Rev-erbx in the neonatal lung
Lab personnel:
Guang Yang, Ph.D. - Lab manager
Maurice Hinson, B.S. - Research Assistant
Patrick Fernando, M.D. - Research Assistant
Funihiko Namba - Post-doctoral Fellow
Selected Publications
Wright, CJ and Dennery, PA: Manipulation of gene expression by oxygen: a primer from bedside to bench. Pediatr Res Pediatr Res 66(1):3-10, 2009.La P, Fernando AP, Zhuang T, Salahudeen A, Yang G, Lin Q, Wright CJ, Dennery, PA: Zinc protoporphyrin regulates cyclin D1 expression independent of heme oxygenase inhibition. J Biol Chem 2009.
Wright CJ, Zhuang T, La P, Yang G, Dennery PA : Hyperoxia-induced NF-kB activation occurs via a maturationally sensitive atypical pathway. Am J Physiol Lung Cell Mol Physiol 296(3):L296-306, 2008.
Lin Q, Weis S, Yang G, Zhuang T, Abate A, Dennery PA: Catalytic inactive heme oxygenase-1 protein regulates its own expression in oxidative stress. Free Rad Biol Med 44(5): 847-855, 2008.
Dennery PA : Effects of oxidative stress on embryonic development. Birth Defects Research Part C. Birth Defects Research Part C: Embryo Today Reviews 81(3): 155-162, 2007.
Alvira CM, Abate A, Yang G, Dennery PA, Rabinowich M: NF-kB activation in the neonatal mouse lung protects against lipopolysaccharide induced inflammation. Am J Resp Crit Care Med 175(8): 805-815, 2007.
Lin Q, Weis S, Yang G, Weng Y-H, Helston R, Rish K, Smith A, Bordner J, Polte T, Gaunitz F, Dennery PA: Heme oxygenase-1 protein localizes to the nucleus and activates transcription factors important in oxidative stress. J Biol Chem 282(28): 20621-20633, 2007.
Lee H, Pespeni M, Roux J, Dennery PA, Matthay MA, and Pittet JF: HO-1 induction restores c-AMP-dependent lung epithelial fluid transport following severe hemorrhage in rats. FASEB J 19(2):287-289, 2005.
Dennery PA, Visner G, Weng YH, Nguyen X, Lu F, Zander D, Yang G: Resistance to hyperoxia with HO-1 disruption: role of iron. Free Rad Biol 34(1): 124-133, 2003.
Dennery PA, Lee CS, Ford BS, Weng YH, Yang G, Rodgers PA: Developmental expression of lung oxygenase isoenzymes. Pediatr Res 53(1): 42-47, 2003.
Yang G, Abate A, George A, Weng Y-H, Dennery PA. : Maturational differences in lung NF-kB activation and role in tolerance to hyperoxia. J Clin Invest 114:669-678, 2004.