Dr. Pryhhuber's research interests are:
1) Inflammatory Lung Disease
2) Interstitial Fibrosis
3) Silicosis
4) Bronchopulmonary Dysplasia.

Up to 300,000 adults and infants per year in the U.S. suffer from acute inflammatory lung diseases such as pneumonia, acute respiratory distress syndrome (ARDS) and respiratory distress of prematurity, while many times that number suffer from chronic, fibrotic lung disease. The proinflammatory cytokine, tumor necrosis factor-a (TNF), is a major pathogenic factor in these acute and chronic lung diseases. Recent discoveries advanced understanding of TNF signaling mechanisms that account for the highly pleiotropic and cell type specific effects of the cytokine. Dr. Pryhuber's laboratory is applying these advances in molecular biology to study how TNF and oxidant stress interact to alter pulmonary cell survival, gene expression and function, with an ultimate goal of improving therapy for inflammatory lung disease.

In her laboratory, cell culture and whole animal models are being utilized to determine signaling mechanisms by which members of the NGF/TNF receptor superfamily, of which TNF receptor I and II (TNFRI and TNFRII) are representative, regulate gene expression, inflammation and apoptosis in the lung. They recently demonstrated marked induction of TNF receptor associated factors (TRAF) and Inhibitor of Apoptosis Proteins (IAPs) by TNF in pulmonary epithelial cells in vitro, in mouse lung following intratracheal TNF treatment and in inflamed human and baboon lung tissue. They are pursing studies to establish cellular and developmental localization, regulation and function of the TRAF-1 and cIAP proteins in lung, as well as their role in TNF-induced proliferation, programmed cell death and transcription factor AP-1 and NFkB activation. Effects of TNF on pulmonary cell function are also being studied in whole animal models. Structural and biochemical abnormalities are measured following exposure of "knock-out" transgenic mice, in which gene expression of either of the TNF receptors or of a signal transduction intermediate protein, such as TRAF1, is prevented, to intratracheal administration of TNF, silica or hyperoxia, in order to understand mechanisms of TNF mediated injury and repair.

• 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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• Popova AP, Bentley JK, Anyanwu AC, Richardson MN, Linn MJ, Lei J, Wong EJ, Goldsmith AM, Pryhuber GS, Hershenson MB. Glycogen synthase kinase-3ß/ß-catenin signaling regulates neonatal lung mesenchymal stromal cell myofibroblastic differentiation. Am J Physiol Lung Cell Mol Physiol. 2012 Sep; 303(5):L439-48.
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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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• Bozyk PD, Bentley JK, Popova AP, Anyanwu AC, Linn MD, Goldsmith AM, Pryhuber GS, Moore BB, Hershenson MB. Neonatal periostin knockout mice are protected from hyperoxia-induced alveolar simplication. PLoS One. 2012; 7(2):e31336.
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• Hwang JW, Rajendrasozhan S, Yao H, Chung S, Sundar IK, Huyck HL, Pryhuber GS, Kinnula VL, Rahman I. FOXO3 deficiency leads to increased susceptibility to cigarette smoke-induced inflammation, airspace enlargement, and chronic obstructive pulmonary disease. J Immunol. 2011 Jul 15; 187(2):987-98.
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• Papuga MO, Kwok E, You Z, Rubery PT, Dougherty PE, Pryhuber G, Beck CA, Hilton MJ, Awad HA, Schwarz EM. TNF is required for the induction but not the maintenance of compression-induced BME signals in murine tail vertebrae: limitations of anti-TNF therapy for degenerative disc disease. J Orthop Res. 2011 Sep; 29(9):1367-74.
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• Scheible K, Zhang G, Baer J, Azadniv M, Lambert K, Pryhuber G, Treanor JJ, Topham DJ. CD8+ T cell immunity to 2009 pandemic and seasonal H1N1 influenza viruses. Vaccine. 2011 Mar 3; 29(11):2159-68.
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• Pressman EK, Thornburg LL, Glantz JC, Earhart A, Wall PD, Ashraf M, Pryhuber GS, Woods JR. Inflammatory cytokines and antioxidants in midtrimester amniotic fluid: correlation with pregnancy outcome. Am J Obstet Gynecol. 2011 Feb; 204(2):155.e1-7.
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• Stevens TP, Dylag A, Panthagani I, Pryhuber G, Halterman J. Effect of cumulative oxygen exposure on respiratory symptoms during infancy among VLBW infants without bronchopulmonary dysplasia. Pediatr Pulmonol. 2010 Apr; 45(4):371-9.
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• Saperstein S, Huyck H, Kimball E, Johnston C, Finkelstein J, Pryhuber G. The effects of interleukin-1beta in tumor necrosis factor-alpha-induced acute pulmonary inflammation in mice. Mediators Inflamm. 2009; 2009:958658.
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• Saperstein S, Chen L, Oakes D, Pryhuber G, Finkelstein J. IL-1beta augments TNF-alpha-mediated inflammatory responses from lung epithelial cells. J Interferon Cytokine Res. 2009 May; 29(5):273-84.
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• Pang J, Hoefen R, Pryhuber GS, Wang J, Yin G, White RJ, Xu X, O'Dell MR, Mohan A, Michaloski H, Massett MP, Yan C, Berk BC. G-protein-coupled receptor kinase interacting protein-1 is required for pulmonary vascular development. Circulation. 2009 Mar 24; 119(11):1524-32.
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• Pryhuber GS, Huyck HL, Bhagwat S, O'Reilly MA, Finkelstein JN, Gigliotti F, Wright TW. Parenchymal cell TNF receptors contribute to inflammatory cell recruitment and respiratory failure in Pneumocystis carinii-induced pneumonia. J Immunol. 2008 Jul 15; 181(2):1409-19.
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• Raghavendran K, Pryhuber GS, Chess PR, Davidson BA, Knight PR, Notter RH. Pharmacotherapy of acute lung injury and acute respiratory distress syndrome. Curr Med Chem. 2008; 15(19):1911-24.
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• Chess PR, D'Angio CT, Pryhuber GS, Maniscalco WM. Pathogenesis of bronchopulmonary dysplasia. Semin Perinatol. 2006 Aug; 30(4):171-8.
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• Clifton DR, Rydkina E, Huyck H, Pryhuber G, Freeman RS, Silverman DJ, Sahni SK. Expression and secretion of chemotactic cytokines IL-8 and MCP-1 by human endothelial cells after Rickettsia rickettsii infection: regulation by nuclear transcription factor NF-kappaB. Int J Med Microbiol. 2005 Aug; 295(4):267-78.
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• Pryhuber GS, Huyck HL, Roper JM, Cornejo J, O'Reilly MA, Pierce RH, Tsitsikov EN. Acute tumor necrosis factor-alpha-induced liver injury in the absence of tumor necrosis factor receptor-associated factor 1 gene expression. Am J Pathol. 2005 Jun; 166(6):1637-45.
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• Lee MK, Pryhuber GS, Schwarz MA, Smith SM, Pavlova Z, Sunday ME. Developmental regulation of p66Shc is altered by bronchopulmonary dysplasia in baboons and humans. Am J Respir Crit Care Med. 2005 Jun 15; 171(12):1384-94.
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• Wright TW, Pryhuber GS, Chess PR, Wang Z, Notter RH, Gigliotti F. TNF receptor signaling contributes to chemokine secretion, inflammation, and respiratory deficits during Pneumocystis pneumonia. J Immunol. 2004 Feb 15; 172(4):2511-21.
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• Pryhuber GS, Huyck HL, Baggs R, Oberdörster G, Finkelstein JN. Induction of chemokines by low-dose intratracheal silica is reduced in TNFR I (p55) null mice. Toxicol Sci. 2003 Mar; 72(1):150-7.
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• Mabanta CG, Pryhuber GS, Weinberg GA, Phelps DL. Erythromycin for the prevention of chronic lung disease in intubated preterm infants at risk for, or colonized or infected with Ureaplasma urealyticum. Cochrane Database Syst Rev. 2003; (4):CD003744.
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• Reynolds SD, Reynolds PR, Pryhuber GS, Finder JD, Stripp BR. Secretoglobins SCGB3A1 and SCGB3A2 define secretory cell subsets in mouse and human airways. Am J Respir Crit Care Med. 2002 Dec 1; 166(11):1498-509.
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• Maniscalco WM, Watkins RH, Pryhuber GS, Bhatt A, Shea C, Huyck H. Angiogenic factors and alveolar vasculature: development and alterations by injury in very premature baboons. Am J Physiol Lung Cell Mol Physiol. 2002 Apr; 282(4):L811-23.
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• Bhatt AJ, Pryhuber GS, Huyck H, Watkins RH, Metlay LA, Maniscalco WM. Disrupted pulmonary vasculature and decreased vascular endothelial growth factor, Flt-1, and TIE-2 in human infants dying with bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001 Nov 15; 164(10 Pt 1):1971-80.
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• O'Reilly MA, Staversky RJ, Huyck HL, Watkins RH, LoMonaco MB, D'Angio CT, Baggs RB, Maniscalco WM, Pryhuber GS. Bcl-2 family gene expression during severe hyperoxia induced lung injury. Lab Invest. 2000 Dec; 80(12):1845-54.
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• Uy IP, Pryhuber GS, Chess PR, Notter RH. Combined-modality therapy with inhaled nitric oxide and exogenous surfactant in term infants with acute respiratory failure. Pediatr Crit Care Med. 2000 Oct; 1(2):107-10.
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• Pryhuber GS, O'Brien DP, Baggs R, Phipps R, Huyck H, Sanz I, Nahm MH. Ablation of tumor necrosis factor receptor type I (p55) alters oxygen-induced lung injury. Am J Physiol Lung Cell Mol Physiol. 2000 May; 278(5):L1082-90.
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• Pryhuber GS, Huyck HL, Staversky RJ, Finkelstein JN, O'Reilly MA. Tumor necrosis factor-alpha-induced lung cell expression of antiapoptotic genes TRAF1 and cIAP2. Am J Respir Cell Mol Biol. 2000 Feb; 22(2):150-6.
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• Khalak R, Huyck HL, Pryhuber GS. Antagonistic effects of pyrrolidine dithiocarbamate and N-acetyl-L-cysteine on surfactant protein A and B mRNAs. Exp Lung Res. 1999 Sep; 25(6):479-93.
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• Pryhuber GS. Regulation and function of pulmonary surfactant protein B. Mol Genet Metab. 1998 Aug; 64(4):217-28.
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• Pryhuber GS, Khalak R, Zhao Q. Regulation of surfactant proteins A and B by TNF-alpha and phorbol ester independent of NF-kappa B. Am J Physiol. 1998 Feb; 274(2 Pt 1):L289-95.
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• O'Reilly MA, Stripp BR, Pryhuber GS. Epithelial-mesenchymal interactions in the alteration of gene expression and morphology following lung injury. Microsc Res Tech. 1997 Sep 1; 38(5):473-9.
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• Pryhuber GS, Bachurski C, Hirsch R, Bacon A, Whitsett JA. Tumor necrosis factor-alpha decreases surfactant protein B mRNA in murine lung. Am J Physiol. 1996 May; 270(5 Pt 1):L714-21.
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• Bachurski CJ, Pryhuber GS, Glasser SW, Kelly SE, Whitsett JA. Tumor necrosis factor-alpha inhibits surfactant protein C gene transcription. J Biol Chem. 1995 Aug 18; 270(33):19402-7.
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• Pryhuber GS, Church SL, Kroft T, Panchal A, Whitsett JA. 3'-untranslated region of SP-B mRNA mediates inhibitory effects of TPA and TNF-alpha on SP-B expression. Am J Physiol. 1994 Jul; 267(1 Pt 1):L16-24.
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• Whitsett JA, Clark JC, Wispé JR, Pryhuber GS. Effects of TNF-alpha and phorbol ester on human surfactant protein and MnSOD gene transcription in vitro. Am J Physiol. 1992 Jun; 262(6 Pt 1):L688-93.
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• Pryhuber GS, Hull WM, Fink I, McMahan MJ, Whitsett JA. Ontogeny of surfactant proteins A and B in human amniotic fluid as indices of fetal lung maturity. Pediatr Res. 1991 Dec; 30(6):597-605.
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• Pryhuber GS, O'Reilly MA, Clark JC, Hull WM, Fink I, Whitsett JA. Phorbol ester inhibits surfactant protein SP-A and SP-B expression. J Biol Chem. 1990 Dec 5; 265(34):20822-8.
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