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Thomas Jefferson University - Omar Tliba, Ph.D.
Omar Tliba, Ph.D.

Jefferson School of Pharmacy
Thomas Jefferson University
Jefferson School of Pharmacy
Associate Professor, Department of Pharmaceutical Sciences

Mailing Address
Health Profession Academic Building, 901 Walnut Street, Rm 910
Philadelphia, Pennsylvania 19107
United States
Contact Information
Phone: 215-503-7467
Fax: 215-503-9052
Omar.Tliba@jefferson.edu
Qualifications
Ms, Biomedical Sciences, University of Rennes I, France, 1997
Ms, Immunology, Institut pasteur, Paris, 1998
Ph.D., Immunology, University of Francois Rabellais, Tours, France, 2001

Biomedical Research Grant Award, American Lung Association 2007-2009
Parker B. Francis Fellowship Award 2007-2010
Member, American Association of Immunologists 2004-2006
Member, American Society for Pharmacology and Experimental Therapeutics, 2008-present
Member, American Thoracic Society, 2008-present
Editorial board member, American Journal of Respiratory Cell & Molecular Biology, 2009-present
Editorial board member, Toxicogenomics, 2011-present
Associate Editor, BMC immunology, 2010-present
Expertise and Research Interests
The recent therapeutic benefit in severe asthmatics provided by bronchial thermoplasty, a therapy that attenuates bronchoconstriction via reduction of airway smooth muscle (ASM) mass, has strongly supported the notion that ASM is a key player in the pathogenesis of asthma. ASM could also participate in the progression of asthma by secreting pro-inflammatory mediators reported both in cultured cells and in bronchial biopsies. My research interest includes airway smooth muscle biology, glucocorticoid signaling, and glucocorticoid resistance. Current research efforts are focused in three major areas:

1. Use ASM cells as a model to gain mechanistic insight in the development of steroid insensitivity in severe asthma. While much research aimed at understanding the basis of insensitivity to glucocorticoid therapy in severe asthmatics focused on the role of immune cells, little has been done to clarify the role of ASM cells. Recent studies performed on bronchial biopsies from asthmatics treated with inhaled or oral glucocorticoids showed a persistent expression of chemokines in ASM bundles. The expression of these genes correlated with the severity of asthma. Our previous studies replicated this finding in vitro using cultured human ASM cells. The induction of pro-asthmatic genes is less sensitive to inhibition by glucocorticoids when such induction was triggered by TNFa and IFNg combination. We will use ASM as a model to further define the mechanisms involved in steroid insensitivity.

2. Characterize the mechanisms that regulate glucocorticoid receptor phosphorylation with a primary focus on the role of Mitogen-Activated Protein Kinase (MAPK) pathways and serine/threonine protein phosphatases (PPs). Phosphorylation of glucocorticoid receptor (GR) on various residues such as serine 203 (S203), S211, and S226 plays a key role in determining the strength and duration of GR actions. At present, uncertainty still exists about the nature of the GR phosphorylation-dependent mechanisms regulating the overall cellular responsiveness to glucocorticoid and which particular GR phosphorylation profile is associated with steroid insensitive conditions. We are using various molecular, biochemical, and cellular strategies to better characterize the role of Mitogen-Activated Protein Kinase (MAPK) pathways and serine/threonine protein phosphatases (PPs) that regulate GR phosphorylation, and thus function, in airway cells with a long-term goal of providing new insight into therapies aiming at restoring steroid responsiveness in patients with severe asthma.

3. Expression and function of glucocorticoid-target genes in airway cells. These studies involve collaborations with a number of investigators and are focused on evaluating the biological role of steroid-target genes in airway cells both in vivo and in vitro using endobronchial tissues isolated from asthmatics with varying degrees of disease severity. Our long-term goal is to integrate the biological effects of such genes in the evaluation of inhaled glucocorticoids efficacy in asthmatic patients.
Other Expertise
Transcriptional regulation of cytokine functions in airway cells. ASM cells respond to many cytokines, growth factors and lipid mediators to produce a wide array of immuno-modulatory molecules which may in turn orchestrate and perpetuate the disease process in asthma. Our goals are to identify intracellular signaling pathways by which cytokines modulate or induce these cellular responses. A focus of this project is to investigate the transcriptional and post-transcriptional mechanisms regulating cytokine functions in ASM cells.

Keywords
Glucocorticoid receptor, cytokines, signal transduction, gene expression, phosphorylation, phosphatases, transcription factors, airway smooth muscle, asthma, lung inflammation, airway biology, remodeling.
Publications
  • 1. Tliba O., Sibille P., Boulard C., Chauvin A.: Local hepatic immune response in rats during primary infection with Fasciola hepatica. Parasite 7(1): 9-18, Mar 2000.
  • 2. Tliba O., Sibille P., Boulard C., Chauvin A.: Early hepatic cytokine mRNA expression in experimental rat fasciolosis. Veterinary Parasitology 103(3): 237-49, Jan 2002.
  • 3. Tliba O., Chauvin A., Le Vern Y., Boulard C., Sbille P.: Evaluation of the hepatic NK cell response during the early phase of Fasciola hepatica infection in rats. Veterinary Research 33(3): 327-32, May-Jun 2002.
  • 4. Tliba O., Moire N., Le Vern Y., Boulard C., Chauvin A., Sibille P.: Early hepatic immune response in rats infected with Fasciola hepatica. Veterinary Research 33(3): 261-70, May-Jun 2002.
  • 5. Amrani Y., Tliba O., Choubey D., Huang CD., Krymskaya VP., Eszterhas A., Lazaar AL., Panettieri RA Jr.: IFN-gamma inhibits human airway smooth muscle cell proliferation by modulating the E2F-1/Rb pathway. American Journal of Physiology - Lung Cellular & Molecular Physiology 284(6): L1063-71, Jun 2003.
  • 6. Huang CD., Tliba O., Panettieri RA Jr., Amrani Y.: Bradykinin induces interleukin-6 production in human airway smooth muscle cells: modulation by Th2 cytokines and dexamethasone. American Journal of Respiratory Cell & Molecular Biology 28(3): 330-8, Mar 2003.
  • 7. Chen H., Tliba O., Van Besien CR., Panettieri RA Jr., Amrani Y.: TNF-[alpha] modulates murine tracheal rings responsiveness to G-protein-coupled receptor agonists and KCl. Journal of Applied Physiology 95(2): 864-72; discussion 863, Aug 2003.
  • 8. Tliba O., Tliba S., Da Huang C., Hoffman RK., DeLong P., Panettieri RA Jr., Amrani Y.: Tumor necrosis factor alpha modulates airway smooth muscle function via the autocrine action of interferon beta. Journal of Biological Chemistry 278(50): 50615-23, Dec 12 2003.
  • 9. Tliba O., Deshpande D., Chen H., Van Besien C., Kannan M., Panettieri RA Jr., Amrani Y.: IL-13 enhances agonist-evoked calcium signals and contractile responses in airway smooth muscle. British Journal of Pharmacology 140(7): 1159-62, Dec 2003.
  • 10. Kazi AS., Lotfi S., Goncharova EA., Tliba O., Amrani Y., Krymskaya VP., Lazaar AL.: Vascular endothelial growth factor-induced secretion of fibronectin is ERK dependent. American Journal of Physiology - Lung Cellular & Molecular Physiology 286(3): L539-45, Mar 2004.
  • 11. Amrani Y., Tliba O., Deshpande DA., Walseth TF., Kannan MS., Panettieri RA Jr.: Bronchial hyperresponsiveness: insights into new signaling molecules. Current Opinion in Pharmacology 4(3): 230-4, Jun 2004.
  • 12. Tliba O., Panettieri RA Jr., Tliba S., Walseth TF., Amrani Y.: Tumor necrosis factor-alpha differentially regulates the expression of proinflammatory genes in human airway smooth muscle cells by activation of interferon-beta-dependent CD38 pathway. Molecular Pharmacology 66(2): 322-9, Aug 2004.
  • 13. Howarth PH., Knox AJ., Amrani Y., Tliba O., Panettieri RA Jr., Johnson M.: Synthetic responses in airway smooth muscle. [Review] [161 refs] Journal of Allergy & Clinical Immunology 114(2 Suppl): S32-50, Aug 2004.
  • 14. Sibille P., Tliba O., Boulard C. : Early and transient cytotoxic response of peritoneal cells from Fasciola hepatica-infected rats: transient fasciolicide activity of infected-rat peritoneal cells. Veterinary Research 35(5): 573-84, Sep-Oct 2004.
  • 15. Syed F., Panettieri RA Jr., Tliba O., Huang C., Li K., Bracht M., Amegadzie B., Griswold D., Li L., Amrani Y.: The effect of IL-13 and IL-13R130Q, a naturally occurring IL-13 polymorphism, on the gene expression of human airway smooth muscle cells. Respiratory Research 6: 9, May 2005.
  • 16. Kim JH., Jain D., Tliba O., Yang B., Jester WF Jr., Panettieri RA Jr., Amrani Y., Pure E.: TGF-beta potentiates airway smooth muscle responsiveness to bradykinin.[see comment] American Journal of Physiology - Lung Cellular & Molecular Physiology 289(4): L511-20, Oct 2005.
  • 17. Huang CD., Ammit AJ., Tliba O., Kuo HP., Penn RB., Panettieri RA Jr., Amrani Y.: G-protein-coupled receptor agonists differentially regulate basal or tumor necrosis factor-alpha-stimulated activation of interleukin-6 and RANTES in human airway smooth muscle cells. Journal of Biomedical Science 12(5): 763-76, Oct 2005.
  • 18. Tliba O., Cidlowski JA., Amrani Y.: CD38 expression is insensitive to steroid action in cells treated with tumor necrosis factor-alpha and interferon-gamma by a mechanism involving the up-regulation of the glucocorticoid receptor beta isoform. Molecular Pharmacology 69(2): 588-96, Feb 2006.
  • 19. Keslacy S., Tliba O., Baidouri H., Amrani Y.: Inhibition of tumor necrosis factor-alpha-inducible inflammatory genes by interferon-gamma is associated with altered nuclear factor-kappaB transactivation and enhanced histone deacetylase activity. Molecular Pharmacology 71(2): 609-18, Feb 2007.
  • 20. Tliba O, Damera G, Banerjee A, Gu Su, Baidouri H, Keslacy S, Amrani Y: Cytokines Induce an Early Steroid Resistance in Airway Smooth Muscle Cells: Novel Role of IRF-1. American Journal of Respiratory Cell and Molecular Biology. American Thoracic Society, 38(4): 463-72, April 2008.
  • 21. Goncharova EA, Goncharov DA, Chisolm A, Spaits MS, Lim PN, Cesarone G, Khavin I, Tliba O, Amrani Y, Panettieri RA Jr, Krymskaya VP. : Interferon beta augments tuberous sclerosis complex 2 (TSC2)-dependent inhibition of TSC2-null ELT3 and human lymphangioleiomyomatosis-derived cell proliferation. Mol Pharmacol 73(3): 778-88, March 2008.
  • 22. Tliba O & Amrani Y: Airway Smooth Muscle Cell as an Inflammatory Cell: Lesson Learned from IFN Signaling Pathways. Proc Am Thorac Soc. 1(5(1)): 106-12. Jan 2008.
  • 23. Tliba O, Amrani Y, Pannettieri RA: Is Airway Smooth Muscle the "Missing Link" Modulating Airway Inflammation in Asthma? Chest 133(1): 236-42, Jan 2008.
  • 24. Jain D, Keslacy S, Tliba O, Cao Y, Kierstein S, Amin K, Panettieri RA Jr, Haczku A, Amrani Y.: Essential role of IFNbeta and CD38 in TNF-alpha-induced airway smooth muscle hyper-responsiveness. Immunobiology 213(6): 499-509, June 2008.
  • 25. Banerjee A, Damera G, Bhandare R, Gu S, Sanchez Y, Panettieri R, Tliba O.: Vitamin D and glucocorticoids differentially modulate chemokine expression in human airway smooth muscle cells. British Journal of Pharmacology. 2008 Sep;155(1):84-92.
  • 26. Tliba O, Panettieri RA: Regulation of Inflammation by Airway Smooth Muscle. Current Allergy/Asthma Reports . 8(3): 262-8, May 2008.
  • 27. Tliba O, Panettieri Jr RA. Noncontractile Functions of Airway Smooth Muscle Cells in Asthma. Annu Rev Physiol. 2009;71:509-35.
  • 28. Damera G, Tliba O, Panettieri RA Jr. Airway smooth muscle as an immunomodulatory cell. Pulm Pharmacol Ther. 2009 Oct;22(5):353-9.
  • 29. Clarke D, Damera G, Sukkar MB, Tliba O. Transcriptional regulation of cytokine function in airway smooth muscle cells. Pulm Pharmacol Ther. 2009 Oct;22(5):436-45.
  • 30. Bailey M, Kierstein S, Spaits M, Tliba O, Sheridan JF, Panettieri RA, Haczku A. Social stress enhances allergen-induced airway inflammation in mice and inhibits corticosteroid responsiveness of cytokine production. Journal of Immunology. Immunol. 2009 Jun 15;182(12):7888-96.
  • 31. Goncharova EA, Goncharov DA, Damera G, Tliba O, Amrani Y, Panettieri RA Jr, Krymskaya VP. Signal transducer and activator of transcription 3 is required for abnormal proliferation and survival of TSC2-deficient cells: relevance to pulmonary lymphangioleiomyomatosis. Mol Pharmacol. 2009 Oct;76(4):766-77
  • 32. Damera G, Fogle HW, Lim P, Goncharova EA, Zhao H, Banerjee A, Tliba O, Krymskaya VP, Panettieri RA Jr. Vitamin D inhibits growth of human airway smooth muscle cells through growth factor-induced phosphorylation of retinoblastoma protein and checkpoint kinase 1. Br J Pharmacol. 2009 Nov;158(6):1429-41. Br J Pharmacol. 2009 Nov;158(6):1429-41.
  • 33. Bhandare R, Damera G, Banerjee A, Flammer JR, Keslacy S, Rogatsky I, Panettieri RA, Amrani Y, Tliba O. Glucocorticoid receptor interacting protein-1 restores glucocorticoid responsiveness in steroid-resistant airway structural cells.Am J Respir Cell Mol Biol. Am J Respir Cell Mol Biol. 2010 Jan;42(1):9-15.
  • 34. Durham A, Adcock IM, Tliba O. Steroid resistance in severe asthma: current mechanisms and future treatment. Curr Pharm Des. 2011;17(7):674-84.
  • 35. Bouazza B, Krytska K, Debba-Pavard M, Amrani Y, Honkanen RE, Tran J, Tliba O. Cytokines Alter Glucocorticoid Receptor Phosphorylation in Airway Cells: Role of Phosphatases. Am J Respir Cell Mol Biol. 2012 Oct;47(4):464-73
  • 36. Chachi L, Shikotra A, Duffy SM, Tliba O, Brightling C, Bradding P, Amrani Y.Functional KCa3.1 Channels Regulate Steroid Insensitivity in Bronchial Smooth Muscle Cells. J Immunol. 2013 Sep 1;191(5):2624-36
  • 37. Bouazza B, Debba-Pavard M, Amrani Y, Isaacs L, O'Connell D, Ahamed S, Formella D, Tliba O. Basal p38 MAPK Regulates Unliganded Glucocorticoid Receptor Function in Airway Smooth Muscle Cells. Am J Respir Cell Mol Biol. 2013 Sep 11. [Epub ahead of print]

Individual Expertise profile of Omar Tliba, Ph.D., Copyright © Omar Tliba, Ph.D..
Last Updated by Omar Tliba, Ph.D. : Sunday, July 1, 2012 8:22:33 AM



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