Selected Publications

Environmental Genetics Group

Genetic Mechanisms of Susceptibility to Ozone-induced Lung Inflammation

1. Kleeberger SR, RC Levitt, L-Y Zhang, M Longphre, J Harkema, A Jedlicka, SM Eleff, D DiSilvestre, and KJ Holroyd.  Linkage analysis of susceptibility to ozone-induced lung inflammation in inbred mice.  Nature Genetics 17:475-478, 1997.  [see also, News & Views: The genetics of air pollution, JM Drazen and DR Beier, Nature Genetics 17:365-366, 1997] [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9398854)
2. Bauer A, A Malkinson, and SR Kleeberger. Susceptibility to neoplastic and non-neoplastic pulmonary diseases in mice: genetic similarities.  Am J Physiol Lung Cell Mol Physiol 287:L685-L703, 2004. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15355860)
3. Backus-Hazzard GS, R Howden, and SR Kleeberger. Genetic susceptibility to ozone-induced lung inflammation in animal models of asthma. Curr Opin Allergy Clin Immunol 4:349-353, 2004.
4. Kleeberger SR, and DA Schwartz.  From quantitative trait locus to gene: a work in progress (editorial).  Am J Resp Crit Care Med 171:804-05, 2005. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15817805)
5. Bauer AK, D Dixon, L Miller-DeGraf, C Walker, A Malkinson, and SR Kleeberger Toll-like receptor 4 in butylated hydroxytoluene-induced mouse pulmonary inflammation and tumorigenesis. J Natl Cancer Inst (JNCI) 97:1778-1781, 2005. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16333033)
6. Cho HY, and SR Kleeberger.  Genetic mechanisms of susceptibility to oxidative lung injury in mice.  Free Rad Biol Med 42;433-445, 2007. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17275675)
7. Dahl M, AK Bauer, M Arredouani, R Soininen, K Trygvasson, SR Kleeberger, and L Kobzik.  Protection against inhaled oxidants through scavenging of oxidized lipids by macrophage receptors MARCO and SR-AI/II.  J Clin Invest, 117; 757-764, 2007.
8. Cho HY, AE Jedlicka, LY Zhang, and SR Kleeberger.  Tumor necrosis factor-a receptor-mediated cell signaling after ozone exposure in mice.  Am J Respir Crit Care Med, in press.
9. Lay JC, NE Alexis, SR Kleeberger, RAS Roubey, BD Harris, PA Bromberg, MJ Hazucha, RB Devlin, and DB Peden.  J Allergy Clin Immunol, in revision.

The Role of NRF2 and Related Genes in Susceptibility to Lung Injury and Disease

1. Reddy NM, Kleeberger SR, Bream JH, Fallon PG, Kensler TW, Yamamoto M, and SP Reddy. Genetic disruption of Nrf2 compromises cell-cycle progression by impairing GSH-induced redox signaling. Oncogene 27:5821-5832, 2008. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=18542053)
2. Cho HY, AE Jedlicka, SPM Reddy, TW Kensler, M Yamamoto, LY Zhang, and SR Kleeberger.  Role of NRF2 in protection against hyperoxic lung injury in mice.  Am J Respir Cell Mol Biol 26:175-182, 2002.  [see also, Perspective: The saga of leucine zippers continues, LE Otterbein and AMK Choi, Am J Respir Cell Mol Biol 26:161-163, 2002. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11804867)
3. Cho HY, AE Jedlicka, SPM Reddy, LY Zhang, TW Kensler, and SR Kleeberger.  Linkage analysis of susceptibility to hyperoxia. Nrf2 is a candidate gene.  Am J Respir Cell Mol Biol 26:42-51, 2002. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11751202)
4. Cho HY, SPM Reddy, M Yamamoto, and SR Kleeberger.  The transcription factor NRF2 protects against pulmonary fibrosis.  FASEB J 18:1258-1260, 2004. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15208274)
5. Zhang Q, SR Kleeberger, and SPM Reddy.  DEP-induced fra-1 expression correlates with a distinct activation of AP-1-dependent gene transcription in the lung.  Am J Physiol Lung Cell Mol Physiol 286: L427-36, 2004. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14565943)
6. Papaiahgari S, SR Kleeberger, H-Y Cho, and SP Reddy.  NADPH oxidase and ERK signaling regulate hyperoxia-induced Nrf2-ARE transcriptional response in pulmonary epithelial cells.  J Biol Chem 279:42302-42312, 2004. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15292179)
7. Cho HY, SPM Reddy, A DeBiase, M Yamamoto, and SR Kleeberger.  Gene expression profiling of NRF2-mediated protection against oxidative injury.  Free Radical Biology and Medicine 38:325-343, 2005. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15629862)
8. Papaiahgari S, Q Zhang, SR Kleeberger, HY Cho, and SP Reddy.  Hyperoxia stimulates an Nrf2-ARE transcriptional response via ROS-EGFR-PI3K-Akt/ERK MAP kinase signaling in pulmonary epithelial cells.  Antioxid Redox Signal 8:43-52, 2006. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16487036)
9. Cho H-Y, SP Reddy, and SR Kleeberger.  NRF2 defends the lung from oxidative stress.  Antioxid Redox Signal 8:76-87, 2006. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16487040)
10. Marzec J, JD Christie, SP Reddy, AE Jedlicka, H Vuong, PN Lanken, R Aplenc, T Yamamoto, M Yamamoto, H-Y Cho, and SR Kleeberger.  Functional polymorphisms in the transcription factor NRF2 in humans increase the risk of acute lung injury.  FASEB J, in press. 
11. Machireddy N, SR Kleeberger, HY Cho, M Yamamoto, T Kensler, S Biswal, and SP Reddy.  Nrf2-dependent GSH regulated transcriptional program controls lung type II cell proliferation and protection against oxidative stress.  AJRCMB, in revision.
12. Wang X, DJ Tomso, BN Chorley, HY Cho, VG Cheung, SR Kleeberger, and DA Bell.  Identification of polymorphic antioxidant response elements in the human genome.  Hum Molec Genet, in revision.

Particle-Induced Cardiopulmonary Injury in Mice: Genetic Susceptibility

1. Ohtsuka Y, K Brunson, AE Jedlicka, W Mitzner, GJ Jakab SM Eleff, L-Y Zhang, RW Clarke, and SR Kleeberger.  Genetic linkage analysis of susceptibility to particle exposure in mice. Am J Respir Cell Mol Biol 22:574-581, 2000. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10783129)
2. Howden R, PR Hanlon, JG Petranka, SR Kleeberger, JR Bucher, JK Dunnick, A Nyska, E Murphy.  Ephedrine plus caffeine causes age dependent cardiovascular responses in Fischer 344 rats.  Am J Physiol Heart Circ Physiol 288:H2219-H2224, 2005. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15653753)
3. Kleeberger SR and Y Ohtsuka.  Gene-particulate matter-health interactions.  Toxicol Appl Pharmacol 207:276-281, 2005. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15979667)
4. Cho HY, AE Jedlicka, R Clarke, and SR Kleeberger.  Role of Toll-like receptor-4 in genetic susceptibility to lung injury induced by residual oil fly ash. Physiological Genomics 22:108-117, 2005. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15784698)
5. Walters DM, AA Menezes, JL Ingram, AB Rice, A Nyska, Y Tani, SR Kleeberger, and JC Bonner. Susceptibility of signal transducer and activator of transcription-1-deficient mice to pulmonary fibrogenesis.  Am J Pathology 167:1221-1229, 2005. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16251407)

The Role of Innate Immunity and Oxidant Stress Genes in Viral Infection and Disease Progression

1. Polack FP, MN Teng, PL Collins, GA Prince, M Exner, H Regele, DD Lirman, R Rabold, SJ Hoffman, SR Kleeberger, M Wills-Karp, and RA Karron.  A role for immune complexes in enhanced respiratory syncytial virus disease.  J Exp Med 196:859-865, 2002. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12235218)
2. Polack FP, SJ Hoffman, PL Collins, FR Laham, B Thumar, RM Hendry, PM Murphy, V Randolph, RA Karron, and SR Kleeberger.  The cysteine-rich region of respiratory syncytial virus attachment protein inhibits innate immunity elicited by the virus and endotoxin.  Proc Natl Acad Sci USA 125:8996-9001, 2005. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15956195)
3. Bukreyev A, ME Serra, FR Laham, SR Kleeberger, PL Collins, and FP Polack.  The cysteine-rich region and secreted form of the attachment G glycoprotein of respiratory syncytial virus enhance the cytotoxic T-lymphocyte response despite lacking major histocompatibility complex class I-restricted epitopes.  J Virol 80:5854-5861, 2006. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16731924)
4. Klein MI, S Coviello, G Bauer, A Benitez, MP Schiatti, MF Delgado, ME Serra, L Novalli, SR Kleeberger, and FP Polack.  The impact of infection with human metapneumovirus and other viruses in young infants and children at high risk for severe pulmonary disease.  J Infect Dis 193:1544-1551, 2006. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16652283)
5. Melendi GA, SJ Hoffman, RA Karron, PM Irusta, FR Laham, A Humbles, B Schofield, C Pan, R Rabold, B Thumar, A Thumar, NP Gerard, W Mitzner, SR Barnum, C Gerard, SR Kleeberger, and FP Polack.  C5 modulates airways hyperreactivity and pulmonary eosinophilia during enhanced respiratory syncytial virus disease by decreasing C3a receptor expression.  J Virol 81:991-999, 2007. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17079327)
6. Melendi GA, FR Laham, AC Monsalvo, JM Casellas, V Israele, NR Polack, SR Kleeberger, and FP Polack.  Virus-specific cytokine signatures in the respiratory tract during primary infection in infancts.  Pediatrics, in press.
7. Ciencewicki J, S Trivedi, SR Kleeberger. Oxidants and the pathogenesis of lung diseases. J Allergy Clin Immunol 122:456-470, 2008. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=18774381)
8. Klein MI, Bergel E, Gibbons L, Coviello s, Bauer G, Benitez A, Serra ME, Delgado MF, Melendi GA, Rodriguez S, Kleeberger SR, Polack FP. Differential gender response to respiratory infections and to the protective effect of breast milk in preterm infants. Pediatrics 2008 121(6):e1510-e1516. [Abstract]

Gene-Environment Interaction and Disease Pathogenesis: Translational Studies

1. Nicolaides NC, KJ Holroyd, SL Ewart, SM Eleff, MB Kiser, CR Dragwa, S Sullivan, L Grasso, LY Zhang, C Messler, T Zhou, SR Kleeberger, K Buetow, and RC Levitt.  Interleukin-9: a candidate gene for asthma.  Proc Natl Acad Sci USA 94:13175-13180, 1997. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9371819)
2. Nadif R, A Jedlicka, M Mintz, J-P Bertrand, SR Kleeberger, and F Kauffmann.  Effect of TNF and LTA polymorphisms on biological markers of response to oxidative stimuli in coal miners: a model of gene-environment interaction. Tumour necrosis factor and lymphotoxin alpha. J Med Genetics 40: 96-103, 2003. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12566517)
3. Sarpong SB, LY Zhang, and SR Kleeberger.  A novel mouse model of experimental asthma.  Int Arch Allergy Immunol 132: 346-54, 2003. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14707466)
4. Lightfoot JT, MJ Turner, M Daves, A Vordermark, and SR Kleeberger.  Genetic influence on daily wheel running activity level.  Physiological Genomics 19: 270-276, 2004. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15383638)
5. Kleeberger SR, and D Peden.  Gene-environment interactions in asthma and other respiratory diseases.  Ann Rev Med 56:383-400, 2005. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15660518)
6. Brown RH, RG Hamilton, M Mintz, AE Jedlicka, AL Scott, and SR Kleeberger. Genetic predisposition to latex allergy: role of interleukin 13 and interleukin 18.  Anesthesiology 102:496-502, 2005. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15731584)
7. Turner MJ, SR Kleeberger, and JT Lightfoot. Influence of genetic background on daily running-wheel activity differs with aging.  Physiological Genomics 22:76-85, 2005. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15855385)
8. Nadif R, M Mintz, A Jedlicka, J-P Bertrand, SR Kleeberger, and F Kauffmann.  Association of CAT polymorphisms with catalase activity and exposure to environmental oxidative stimuli.  Free Radical Res 39:1345-1350, 2005. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16298864)
9. Nadif R, M Mintz, S Rivas-Fuentes, A Jedlicka, E Lavergne, M Rodero, F Kauffmann, C Combadiere, and SR Kleeberger.  Polymorphisms in chemokine and chemokine receptor genes and the development of coal workers’ pneumoconiosis.  Cytokine 33:171-178, 2006. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16524739)
10. Nadif R, M Mintz, J Marzec, A Jedlicka, F Kauffmann, and SR Kleeberger.  IL18 and IL18R1 polymorphisms, lung CT and fibrosis: A longitudinal study in coal miners.  Eur Respir J 28:1100-1105, 2006. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16971411)
11. Lightfoot JT, MJ Turner, AM Kleinfehn, AE Jedlicka, T Oshimura, J Marzec, W Gladwell, LJ Leamy, and SR Kleeberger.  Quantitative train loci (QTL) associated with exercise endurance in inbred mice.  J Appl Physiol, in revision.

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