Premature infant morbidity and mortality often results from pulmonary complications, primarily insufficient lung maturation or alveolar formation. Likewise, many adult lung diseases involve obliteration of the distal respiratory structure. With the advent of clinical means to dramatically improve pre-term infant survival, there has been a growing appreciation of a relationship between developmental complications and susceptibility to chronic lung disease. The broad objectives of Dr. Mariani's laboratory are to identify the genetic mechanisms of susceptibility to chronic lung diseases, particularly focusing upon their developmental antecedents and the influence of environmental factors. Dr. Mariani's research program focuses upon defining regulatory networks involved in lung development and maturation, and which may be perturbed in diseased states. His laboratory uses a combination of animal modeling research and studies of human subjects. He is a leader in the application of gene expression array methods to pulmonary biology and lung disease. Current research projects in the Mariani lab include:

1. Defining genetic regulatory networks contributing to airspace morphogenesis using the FGFR3/4 mutant mouse model of abnormal alveolar formation.

2. Determining the physiological role of PPARg in lung epithelial cells during airspace formation and in lung injury/repair.

3. Investigating the cellular and molecular mechanisms by which the protease inhibitor SERPINE2 contributes to airspace formation and susceptibility to COPD.

This work is currently supported by the NIH and FAMRI.

• Scheible K, Secor-Socha S, Wightman T, Wang H, Mariani TJ, Topham DJ, Pryhuber G, Quataert S. Stability of T cell phenotype and functional assays following heparinized umbilical cord blood collection. Cytometry A. 2012 Nov; 81(11):937-49.
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• Bhattacharya S, Go D, Krenitsky DL, Huyck HL, Solleti SK, Lunger VA, Metlay L, Srisuma S, Wert SE, Mariani TJ, Pryhuber GS. Genome-wide transcriptional profiling reveals connective tissue mast cell accumulation in bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2012 Aug 15; 186(4):349-58.
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• Brehm JM, Hagiwara K, Tesfaigzi Y, Bruse S, Mariani TJ, Bhattacharya S, Boutaoui N, Ziniti JP, Soto-Quiros ME, Avila L, Cho MH, Himes B, Litonjua AA, Jacobson F, Bakke P, Gulsvik A, Anderson WH, Lomas DA, Forno E, Datta S, Silverman EK, Celedón JC. Identification of FGF7 as a novel susceptibility locus for chronic obstructive pulmonary disease. Thorax. 2011 Dec; 66(12):1085-90.
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• Melén E, Kho AT, Sharma S, Gaedigk R, Leeder JS, Mariani TJ, Carey VJ, Weiss ST, Tantisira KG. Expression analysis of asthma candidate genes during human and murine lung development. Respir Res. 2011; 12:86.
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• Reddy NM, Potteti HR, Mariani TJ, Biswal S, Reddy SP. Conditional deletion of nrf2 in airway epithelium exacerbates acute lung injury and impairs the resolution of inflammation. Am J Respir Cell Mol Biol. 2011 Dec; 45(6):1161-8.
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• Bhattacharya S, Tyagi S, Srisuma S, Demeo DL, Shapiro SD, Bueno R, Silverman EK, Reilly JJ, Mariani TJ. Peripheral blood gene expression profiles in COPD subjects. J Clin Bioinforma. 2011; 1(1):12.
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• Himes BE, Klanderman B, Ziniti J, Senter-Sylvia J, Soto-Quiros ME, Avila L, Celedón JC, Lange C, Mariani TJ, Lasky-Su J, Hersh CP, Raby BA, Silverman EK, Weiss ST, Demeo DL. Association of SERPINE2 with asthma. Chest. 2011 Sep; 140(3):667-74.
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• Hersh CP, Silverman EK, Gascon J, Bhattacharya S, Klanderman BJ, Litonjua AA, Lefebvre V, Sparrow D, Reilly JJ, Anderson WH, Lomas DA, Mariani TJ. SOX5 is a candidate gene for chronic obstructive pulmonary disease susceptibility and is necessary for lung development. Am J Respir Crit Care Med. 2011 Jun 1; 183(11):1482-9.
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• Simon DM, Tsai LW, Ingenito EP, Starcher BC, Mariani TJ. PPARgamma deficiency results in reduced lung elastic recoil and abnormalities in airspace distribution. Respir Res. 2010; 11:69.
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• Srisuma S, Bhattacharya S, Simon DM, Solleti SK, Tyagi S, Starcher B, Mariani TJ. Fibroblast growth factor receptors control epithelial-mesenchymal interactions necessary for alveolar elastogenesis. Am J Respir Crit Care Med. 2010 Apr 15; 181(8):838-50.
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• Sharma S, Tantisira K, Carey V, Murphy AJ, Lasky-Su J, Celedón JC, Lazarus R, Klanderman B, Rogers A, Soto-Quirós M, Avila L, Mariani T, Gaedigk R, Leeder S, Torday J, Warburton D, Raby B, Weiss ST. A role for Wnt signaling genes in the pathogenesis of impaired lung function in asthma. Am J Respir Crit Care Med. 2010 Feb 15; 181(4):328-36.
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• Kho AT, Bhattacharya S, Tantisira KG, Carey VJ, Gaedigk R, Leeder JS, Kohane IS, Weiss ST, Mariani TJ. Transcriptomic analysis of human lung development. Am J Respir Crit Care Med. 2010 Jan 1; 181(1):54-63.
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• DeMeo DL, Mariani T, Bhattacharya S, Srisuma S, Lange C, Litonjua A, Bueno R, Pillai SG, Lomas DA, Sparrow D, Shapiro SD, Criner GJ, Kim HP, Chen Z, Choi AM, Reilly J, Silverman EK. Integration of genomic and genetic approaches implicates IREB2 as a COPD susceptibility gene. Am J Hum Genet. 2009 Oct; 85(4):493-502.
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• Bhattacharya S, Mariani TJ. Array of hope: expression profiling identifies disease biomarkers and mechanism. Biochem Soc Trans. 2009 Aug; 37(Pt 4):855-62.
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• Du R, Tantisira K, Carey V, Bhattacharya S, Metje S, Kho AT, Klanderman BJ, Gaedigk R, Lazarus R, Mariani TJ, Leeder JS, Weiss ST. Platform dependence of inference on gene-wise and gene-set involvement in human lung development. BMC Bioinformatics. 2009; 10:189.
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• Blake DJ, Singh A, Kombairaju P, Malhotra D, Mariani TJ, Tuder RM, Gabrielson E, Biswal S. Deletion of Keap1 in the lung attenuates acute cigarette smoke-induced oxidative stress and inflammation. Am J Respir Cell Mol Biol. 2010 May; 42(5):524-36.
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• Bhattacharya S, Srisuma S, Demeo DL, Shapiro SD, Bueno R, Silverman EK, Reilly JJ, Mariani TJ. Molecular biomarkers for quantitative and discrete COPD phenotypes. Am J Respir Cell Mol Biol. 2009 Mar; 40(3):359-67.
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• Kho AT, Bhattacharya S, Mecham BH, Hong J, Kohane IS, Mariani TJ. Expression profiles of the mouse lung identify a molecular signature of time-to-birth. Am J Respir Cell Mol Biol. 2009 Jan; 40(1):47-57.
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• Planagumà A, Kazani S, Marigowda G, Haworth O, Mariani TJ, Israel E, Bleecker ER, Curran-Everett D, Erzurum SC, Calhoun WJ, Castro M, Chung KF, Gaston B, Jarjour NN, Busse WW, Wenzel SE, Levy BD. Airway lipoxin A4 generation and lipoxin A4 receptor expression are decreased in severe asthma. Am J Respir Crit Care Med. 2008 Sep 15; 178(6):574-82.
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• Reynolds SD, Zemke AC, Giangreco A, Brockway BL, Teisanu RM, Drake JA, Mariani T, Di PY, Taketo MM, Stripp BR. Conditional stabilization of beta-catenin expands the pool of lung stem cells. Stem Cells. 2008 May; 26(5):1337-46.
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• Tantisira KG, Silverman ES, Mariani TJ, Xu J, Richter BG, Klanderman BJ, Litonjua AA, Lazarus R, Rosenwasser LJ, Fuhlbrigge AL, Weiss ST. FCER2: a pharmacogenetic basis for severe exacerbations in children with asthma. J Allergy Clin Immunol. 2007 Dec; 120(6):1285-91.
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• Hirakawa H, Pierce RA, Bingol-Karakoc G, Karaaslan C, Weng M, Shi GP, Saad A, Weber E, Mariani TJ, Starcher B, Shapiro SD, Cataltepe S. Cathepsin S deficiency confers protection from neonatal hyperoxia-induced lung injury. Am J Respir Crit Care Med. 2007 Oct 15; 176(8):778-85.
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• Fedulov AV, Leme A, Yang Z, Dahl M, Lim R, Mariani TJ, Kobzik L. Pulmonary exposure to particles during pregnancy causes increased neonatal asthma susceptibility. Am J Respir Cell Mol Biol. 2008 Jan; 38(1):57-67.
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• Simeone-Penney MC, Severgnini M, Tu P, Homer RJ, Mariani TJ, Cohn L, Simon AR. Airway epithelial STAT3 is required for allergic inflammation in a murine model of asthma. J Immunol. 2007 May 15; 178(10):6191-9.
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• Simon DM, Mariani TJ. Role of PPARs and Retinoid X Receptors in the Regulation of Lung Maturation and Development. PPAR Res. 2007; 2007:91240.
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• Bhattacharya S, Srisuma S, Demeo DL, Reilly JJ, Bueno R, Silverman EK, Mariani TJ. Microarray data-based prioritization of chronic obstructive pulmonary disease susceptibility genes. Proc Am Thorac Soc. 2006 Aug; 3(6):472.
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• Simon DM, Arikan MC, Srisuma S, Bhattacharya S, Andalcio T, Shapiro SD, Mariani TJ. Epithelial cell PPARgamma is an endogenous regulator of normal lung maturation and maintenance. Proc Am Thorac Soc. 2006 Aug; 3(6):510-1.
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• DeMeo D, Mariani T, Lange C, Lake S, Litonjua A, Celedón J, Reilly J, Chapman HA, Sparrow D, Spira A, Beane J, Pinto-Plata V, Speizer FE, Shapiro S, Weiss ST, Silverman EK. The SERPINE2 gene is associated with chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2006 Aug; 3(6):502.
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• Chu EK, Cheng J, Foley JS, Mecham BH, Owen CA, Haley KJ, Mariani TJ, Kohane IS, Tschumperlin DJ, Drazen JM. Induction of the plasminogen activator system by mechanical stimulation of human bronchial epithelial cells. Am J Respir Cell Mol Biol. 2006 Dec; 35(6):628-38.
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• Simon DM, Arikan MC, Srisuma S, Bhattacharya S, Tsai LW, Ingenito EP, Gonzalez F, Shapiro SD, Mariani TJ. Epithelial cell PPAR[gamma] contributes to normal lung maturation. FASEB J. 2006 Jul; 20(9):1507-9.
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• Ji H, Houghton AM, Mariani TJ, Perera S, Kim CB, Padera R, Tonon G, McNamara K, Marconcini LA, Hezel A, El-Bardeesy N, Bronson RT, Sugarbaker D, Maser RS, Shapiro SD, Wong KK. K-ras activation generates an inflammatory response in lung tumors. Oncogene. 2006 Mar 30; 25(14):2105-12.
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• Demeo DL, Mariani TJ, Lange C, Srisuma S, Litonjua AA, Celedon JC, Lake SL, Reilly JJ, Chapman HA, Mecham BH, Haley KJ, Sylvia JS, Sparrow D, Spira AE, Beane J, Pinto-Plata V, Speizer FE, Shapiro SD, Weiss ST, Silverman EK. The SERPINE2 gene is associated with chronic obstructive pulmonary disease. Am J Hum Genet. 2006 Feb; 78(2):253-64.
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• Bhattacharya S, Mariani TJ. Transformation of expression intensities across generations of Affymetrix microarrays using sequence matching and regression modeling. Nucleic Acids Res. 2005; 33(18):e157.
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• Arikan MC, Shapiro SD, Mariani TJ. Induction of macrophage elastase (MMP-12) gene expression by statins. J Cell Physiol. 2005 Jul; 204(1):139-45.
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• Mecham BH, Wetmore DZ, Szallasi Z, Sadovsky Y, Kohane I, Mariani TJ. Increased measurement accuracy for sequence-verified microarray probes. Physiol Genomics. 2004 Aug 11; 18(3):308-15.
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• Mecham BH, Klus GT, Strovel J, Augustus M, Byrne D, Bozso P, Wetmore DZ, Mariani TJ, Kohane IS, Szallasi Z. Sequence-matched probes produce increased cross-platform consistency and more reproducible biological results in microarray-based gene expression measurements. Nucleic Acids Res. 2004; 32(9):e74.
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• Mariani TJ, Kaminski N. Gene expression studies in lung development and lung stem cell biology. Curr Top Dev Biol. 2004; 64:57-71.
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• Mariani TJ, Budhraja V, Mecham BH, Gu CC, Watson MA, Sadovsky Y. A variable fold change threshold determines significance for expression microarrays. FASEB J. 2003 Feb; 17(2):321-3.
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• Chest 2002 Scientific Highlights. Abstracts of original investigations and case reports. 2-7 November 2002, San Diego, California, USA. Chest. 2002 Oct; 122(4 Suppl):1S-269S.
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• Zelko IN, Mariani TJ, Folz RJ. Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression. Free Radic Biol Med. 2002 Aug 1; 33(3):337-49.
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• Mariani TJ, Reed JJ, Shapiro SD. Expression profiling of the developing mouse lung: insights into the establishment of the extracellular matrix. Am J Respir Cell Mol Biol. 2002 May; 26(5):541-8.
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• Mariani TJ, Shapiro SD. Thomas A. Neff lecture. Application of expression profiling to the developing lung: identification of putative regulatory networks controlling matrix production. Chest. 2002 Mar; 121(3 Suppl):42S-44S.
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• Motzer RJ, Murphy BA, Bacik J, Schwartz LH, Nanus DM, Mariani T, Loehrer P, Wilding G, Fairclough DL, Cella D, Mazumdar M. Phase III trial of interferon alfa-2a with or without 13-cis-retinoic acid for patients with advanced renal cell carcinoma. J Clin Oncol. 2000 Aug; 18(16):2972-80.
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• Mariani TJ, Arikan MC, Pierce RA. Fibroblast tropoelastin and alpha-smooth-muscle actin expression are repressed by particulate-activated macrophage-derived tumor necrosis factor-alpha in experimental silicosis. Am J Respir Cell Mol Biol. 1999 Aug; 21(2):185-92.
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• Mariani TJ, Sandefur S, Roby JD, Pierce RA. Collagenase-3 induction in rat lung fibroblasts requires the combined effects of tumor necrosis factor-alpha and 12-lipoxygenase metabolites: a model of macrophage-induced, fibroblast-driven extracellular matrix remodeling during inflammatory lung injury. Mol Biol Cell. 1998 Jun; 9(6):1411-24.
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• Mariani TJ, Dunsmore SE, Li Q, Ye X, Pierce RA. Regulation of lung fibroblast tropoelastin expression by alveolar epithelial cells. Am J Physiol. 1998 Jan; 274(1 Pt 1):L47-57.
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• Mariani TJ, Sandefur S, Pierce RA. Elastin in lung development. Exp Lung Res. 1997 Mar-Apr; 23(2):131-45.
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• Mariani TJ, Roby JD, Mecham RP, Parks WC, Crouch E, Pierce RA. Localization of type I procollagen gene expression in silica-induced granulomatous lung disease and implication of transforming growth factor-beta as a mediator of fibrosis. Am J Pathol. 1996 Jan; 148(1):151-64.
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• Mariani TJ, Crouch E, Roby JD, Starcher B, Pierce RA. Increased elastin production in experimental granulomatous lung disease. Am J Pathol. 1995 Oct; 147(4):988-1000.
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• Schwartz E, Feinberg E, Lebwohl M, Mariani TJ, Boyd CD. Ultraviolet radiation increases tropoelastin accumulation by a post-transcriptional mechanism in dermal fibroblasts. J Invest Dermatol. 1995 Jul; 105(1):65-9.
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• Boyd CD, Mariani TJ, Kim Y, Csiszar K. The size heterogeneity of human lysyl oxidase mRNA is due to alternate polyadenylation site and not alternate exon usage. Mol Biol Rep. 1995; 21(2):95-103.
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• Pierce RA, Mariani TJ, Senior RM. Elastin in lung development and disease. Ciba Found Symp. 1995; 192:199-212; discussion 212-4.
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• Csiszar K, Mariani TJ, Gosin JS, Deak SB, Boyd CD. A restriction fragment length polymorphism results in a nonconservative amino acid substitution encoded within the first exon of the human lysyl oxidase gene. Genomics. 1993 May; 16(2):401-6.
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• Mariani TJ, Trackman PC, Kagan HM, Eddy RL, Shows TB, Boyd CD, Deak SB. The complete derived amino acid sequence of human lysyl oxidase and assignment of the gene to chromosome 5 (extensive sequence homology with the murine ras recision gene). Matrix. 1992 Jun; 12(3):242-8.
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• Deak SB, Ricotta JJ, Mariani TJ, Deak ST, Zatina MA, Mackenzie JW, Boyd CD. The role of abnormal type III collagen in the development of common aneurysms. J Vasc Surg. 1992 May; 15(5):926-7.
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• Deak SB, Ricotta JJ, Mariani TJ, Deak ST, Zatina MA, Mackenzie JW, Boyd CD. Abnormalities in the biosynthesis of type III procollagen in cultured skin fibroblasts from two patients with multiple aneurysms. Matrix. 1992 Apr; 12(2):92-100.
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• Rainaldi G, Luccini F, Mariani T. Effect of cocultivation on the levels of spontaneous and induced sister chromatid exchanges in Chinese hamster cells. J Cell Physiol. 1982 Aug; 112(2):281-3.
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• Mariani T, Damhof J, Good RA. Germinal center formation in response to skin grafted across weak and strong histocompatibility (H2) barriers. Adv Exp Med Biol. 1973; 29(0):597-602.
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