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Profile: Brian Knoll

Brian Knoll
Brian J. Knoll, Ph.D.
Associate Professor of Pharmacology
Assistant Dean of Graduate Programs
Department of Pharmacological and Pharmaceutical Sciences
University of Houston College of Pharmacy
Science & Research Bldg. 2, Room 521 D
3455 Cullen Blvd.
College of Pharmacy
Houston, TX 77204-5000
713-743-1299
bknoll@uh.edu

Education

B.S. (Biology), University of Notre Dame, South Bend, Ind.

Ph.D. (Molecular Biology), University of Arizona College of Medicine, Tucson, Ariz.

Postdoctoral Fellowship, Baylor College of Medicine

Master Teacher Fellowship, Baylor College of Medicine

Advanced Immunology Courses, American Association of Immunologists (2004 and 2008)

Research Interests

Effective asthma therapy relies on β-agonist drugs that activate β2-adrenoceptors (β2ARs) on the surfaces of cells in airway smooth muscle and epithelium. β-agonist drugs are effective in acting upon airway smooth muscle to cause bronchodilation, thereby relieving some asthma symptoms.  However, β2-agonists also may act upon airway epithelium to promote inflammation and secretion of mucous in the presence of the proinflammatory cytokine IL-13. Treatment of mice with antagonists of the β2AR, as well as deletion of the β2AR gene, reduces asthma-like symptoms in experimental mice.

We are exploring the mechanisms by which β2AR signaling in airway epithelium causes a proinflammatory effect. As one model, we use primary human airway epithelial cells grown in culture and treated pharmacologically and genetically to modify signal transducing components downstream of the β2AR and the IL-13 receptors. We employ immunoblotting, confocal microscopy, qRT-PCR and other methods to assess gene expression and the activity of signal-transducing molecules. In collaborative studies with the Bond lab, genetically modified mice are used to test hypotheses derived from the experiments with human airway epithelium.

These studies may lead to the development of new therapeutics designed to reduce airway inflammation by blockade of β2AR signaling in airway epithelium.

Selected Publications

Forkuo GS, Kim H, Thanawala VJ, Al-Sawalha N, Valdez D, Joshi R, Parra S, Pera T, Gonnella PA, Knoll BJ, Walker JK, Penn RB, Bond RA. PDE4 Inhibitors Attenuate the Asthma Phenotype Produced by β2-adrenoceptor Agonists in PNMT-KO Mice. Am J Respir Cell Mol Biol. 2016 Feb 24. [Epub ahead of print] PMID: 26909542

Thanawala VJ, Valdez DJ, Joshi R, Forkuo GS, Parra S, Knoll BJ, Bouvier M, Leff P, Bond RA. β-Blockers have differential effects on the murine asthma phenotype. Br J Pharmacol. 2015 Oct;172(20):4833-46. doi: 10.1111/bph.13253. Epub 2015 Oct 13. PMID: 26211486

Al-Sawalha N, Pokkunuri I, Omoluabi O, Kim H, Thanawala VJ, Hernandez A, Bond RA, Knoll BJ. Epinephrine Activation of the β2-Adrenoceptor Is Required for IL-13-Induced Mucin Production in Human Bronchial Epithelial Cells. PLoS One. 2015 Jul 10;10(7):e0132559. doi: 10.1371/journal.pone.0132559. eCollection 2015. PMID: 26161982

Thanawala VJ, Forkuo GS, Al-Sawalha N, Azzegagh Z, Nguyen LP, Eriksen JL, Tuvim MJ, Lowder TW, Dickey BF, Knoll BJ, Walker JK, Bond RA. β2-Adrenoceptor agonists are required for development of the asthma phenotype in a murine model. Am J Respir Cell Mol Biol. 2013 Feb;48(2):220-9. doi: 10.1165/rcmb.2012-0364OC. Epub 2012 Nov 29. PMID: 23204390

Peng, H., Bond, R.A. and Knoll, B.J. (2011). The effects acute and chronic nadalol treatment on β2AR signaling in HEK293 cells. Naunyn-Schmiedeberg Arch. Pharmacol. 383:209-216.

Awwad, H.O., Moore, R.H., Millman, E.E. and Knoll, B.J. (2010). Mutating the dileucine motif of the human β2-adrenoceptor reduces the high initial rate of receptor phosphorylation by GRK without affecting postendocytic sorting. Eur. J. Pharmacol. 635:9-15.

Nguyen, L.P., Lin, R., Omoluabi, O., Hanania, N.A., Tuvim, M.J., Knoll, B.J., Dickey, B.F. and Bond, R.A. (2009) β2-adrenoceptor signaling is required for the development of the asthma phenotype in a murine model. Proc.Nat. Acad. Sci. U.S.A. 106: 2435-2440.

Nguyen, L.P, Omoluabi, O., Parra, S., Frieske, J.M., Clement, C., Ammar-Aouchiche, Z., Ho, S., Knoll, B.J., Tuvim, M.J., Dickey, B.F. and. Bond, R.A. (2008). Chronic exposure to beta-blockers attenuates inflammation and mucin content in a murine asthma model. Am. J. Resp. Cell Molec. Biol. 38:256-262

Millman, E.E., Zhang, H., Zhang, H., Godines, V., Bean, A.J., Knoll, B.J. and Moore, R.H. (2008). Rapid recycling of β2-adrenergic receptors is dependent on the actin cytoskeleton and myosin Vb. Traffic 9:1958-1971.

Lin, R., Peng, H., Nguyen, L.P., Dudekula, N.B., Shardonofsky, F., Knoll, B.J., Parra, S. and Bond, R.A. (2008). Changes in β2 adrenoceptor and other signaling proteins produced by chronic administration of ‘beta –blockers’ in a murine asthma model. Pulm. Pharmacol. Therapeut. 21:115-124

Moore, R.H., Millman, E.E., Godines, V., Hanania, N.A., Tran, T.M., Peng, H., Dickey, B.F., Knoll, B.J. and Clark, R.B. (2007). Salmeterol stimulation dissociates β2-adrenergic receptor phosphorylation and internalization. Am. J. Resp. Cell Molec. Biol. 36: 254-261

Awwad, H., Iyer, V., Rosenfeld, J.L., Millman, E.E., Moore, R.H and Knoll, B.J. (2007). Inhibitors of phosphoinositide 3-kinase cause defects in the postendocytic sorting of β2-adrenergic receptors. Exp. Cell Res. 313: 2586-2596

Tran, T.M., Friedman, J., Baameur, J.F., Knoll, B.J. and Clark, R.B. (2007). Dissociation of β2-adrenergic receptor resensitization from dephosphorylation of the PKA and GRK sites. Molec. Pharmacol. 71: 47-60.

Iyer, V., Tran, T.M., Foster, E., Dai, W., Clark, R.B. and Knoll, B.J. (2006). Differential phosphorylation and dephosphorylation of β2-adrenoceptor sites Ser262 and Ser355,356. Br. J. Pharmacol. 147: 249-259. (with editorial commentary, 147: 235-236).

Vaughan, D.J., Millman, E.E., Godines, V., Friedman, J., Tran, T.M., Dai, W., Knoll, B.J., Clark, R.B. and Moore, R.H. (2006). Role of the G protein-coupled receptor kinase site serine cluster in β2-adrenergic receptor internalization, desensitization, and β-arrestin translocation. J. Biol. Chem. 281: 7684-7692.

Callaerts-Vegh, Z., Evans, K.L., Dudekula, N., Cuba, D., Knoll, B.J., Callaerts, P.F., Giles, H., Shardonofsky, F.R., and Bond, R.A. (2004). Effects of acute and chronic administration of β-adrenoceptor ligands on airway function in a murine model of asthma. Proc. Natl. Acad. Sci. U. S. A. 101: 4948-4953.

Presentations & Abstracts

Al-Sawalha, N., Senny, C., Hernandez, A., Valdaez, D., Pokkunur, I., Thanawala, V., Bond, R.A. and Knoll, B.J. Role of cAMP signaling in mucin production in response to IL-13 in human bronchial epithelial cells. Experimental Biology, San Diego, CA, 2014

Thanawala, V.T., Valdez, D., Al-Sawalha, N., Forkuo, G.S., Knoll, B.J. and Bond, R.A. The signaling-bias of certain β-blockers predicts their therapeutic efficacy in a murine asthma model. 17th World Congress of Basic & Clinical Pharmacology, Cape Town, 2014

Forkuo, G., Thanawala, V.J., Knoll, B.J. and Bond, R.A. The role of the β2-adrenoceptor Gs pathway in the development of the asthma phenotype in murine models. 17th World Congress of Basic & Clinical Pharmacology, Cape Town, 2014

Thanawala, V.J., Forkuo, G., Al-Sawalha, N., Knoll, B.J., Leff P and Bond, R.A. Role of biased signaling by β-blockers in the development of an asthma phenotype in a murine model. Experimental Biology, Boston, MA, 2013

Forkuo, G., Thanawala, V.J., Al-Sawalha, N., Knoll, B.J. and Bond, R.A. The role of the β2-adrenoceptor Gs pathway in the development of the asthma phenotype in murine models. Experimental Biology, Boston, MA, 2013

Al-Sawalha, N., Pokkunuri, I., Bond, R.A. and Knoll, B.J. Pro-inflammatory role of β2- adrenoceptor signaling in human airway epithelial cells in response to IL-13. Experimental Biology, Boston, MA, 2013

Al-Sawalha, N., Pokkunuri, I., Hernandez, A., Bond, R.A. and Knoll, B.J. Mitogen activated protein kinases and cAMP-dependent kinases mediate β2-adrenoceptor dependent mucin MUC5AC expression in normal human bronchial epithelial cells in response to IL-13. British Pharmacological Society Winter Meeting, London, 2012

Forkuo, G.S., Thanawala, V.J., Al-Sawalha, N., Omoluabi, O., Knoll, B.J. and Bond, R.A. β2-agonists are required for the development of the asthma phenotype in murine model of asthma. Lung Research Day, Gulf Coast Consortia, Houston, TX, 2012.

Al-Sawalha, N., Pokkunuri, I., Omoluabi, O., Bond, R.A. and Knoll, B.J. Role of β2-adrenoceptor signaling and mitogen activated protein kinases in IL-13 induced mucus production in human airway epithelial cells. Lung Research Day, Gulf Coast Consortia, Houston, TX, 2012.

Thanawala, V.J., Al-Sawalha, N., Forkuo, G.S., Omoluabi O, Knoll, B.J. and Bond, R.A. Epinephrine is required for the IL-13 induced increase in inflammatory cells in murine airways. Lung Research Day, Gulf Coast Consortia, Houston, TX, 2012. (First Place Winner, Best Poster Competition).

Thanawala, V.J., Al-Sawalha, N., Forkuo, G.S., Omoluabi, O., Knoll, B.J. and Bond, R.A. Epinephrine is required for the IL-13 induced increase in inflammatory cells in murine airways. Experimental Biology, San Diego, CA, 2012

Al-Sawalha, N., Pokkunuri, I., Omoluabi, O., Bond, R.A. and Knoll, B.J. Role of β2-adrenoceptor signaling and mitogen activated protein kinases in IL-13 induced mucus production in human airway epithelial cells. Experimental Biology, San Diego, CA, 2012 (*ASPET Travel Award to NA).

Nguyen, L.P., Tuvim, M.J., Daily, C., McGrath, I.C., Knoll, B.J., Dickey, B.F. and Bond, R.A. The principal site of action of the β2-adrenoceptor in promoting the asthma phenotype is airway epithelium. British Pharmacological Society Winter Meeting, London, 2011

Pokkunuri, I., Nguyen, L.P., Al-Sawalha, N., Omoluabi, O., Dickey, B.F., Bond, R.A. and Knoll, B.J. β2AR signaling in human bronchial epithelial cells is required for IL-13 induced expression of the mucin MUC5AC and secretion of inflammatory chemokines. British Pharmacological Society Winter Meeting, London, 2011

Okulate, A.A., Nguyen, L.P., Omoluabi, O., Gonzalez, J.M., McGrath, J.C., Tuvim, M.J., Bond, R.A., Dickey, B.F. and Knoll, B.J. Blockade or deletion of the β2-Adrenoceptor inhibits IL-13 induced mucous metaplasia in mice and in cultured human airway epithelial cells. University of Houston Undergraduate Research Day (Okulate, A.A.), Fall, 2011

Lin, R., Knoll, B.J. and Bond, R.A. Effect of chronic nadolol treatment on isoproterenol induced mouse tracheal relaxation. Experimental Biology, San Diego, CA, 2008.

Peng, H., Bond, R.A. and Knoll, B.J. Analysis of inverse agonism in the Gs signaling pathway. Experimental Biology, San Diego, CA, 2008.

Nguyen, L.P., Omoluabi, O., Parra, S., Frieske, J.M., Clement, C., Ammar-Aouchiche, Z., Ho, S.B., Knoll, B.J., Tuvim, M.J., Dickey, B.F., and Bond, R.A. Chronic Exposure to Beta-Blockers Attenuates Inflammation and Mucous Metaplasia in a Murine Asthma Model. Experimental Biology, San Diego, CA, 2008.

Lin, R., Parra, S., Chan, B., Frieske, J., Syed, A., Knoll, B.J. and Bond, R.A. Possible mechanisms of the bronchoprotective effect of chronic beta blocker treatment in a murine model of asthma. Experimental Biology, Washington D.C., 2007.

Awwad, H., Iyer, V., Rosenfeld, J.L., Millman, E.E., Moore, R.H and Knoll, B.J. Inhibitors of phosphoinositide 3-kinase cause defects in the postendocytic sorting of β2- adrenergic receptors. 3rd GPCR Satellite Meeting, Experimental Biology, Washington, D.C., 2007.

Parra, S., Rodriguez, C., Lin, R., Omoluabi, Z., Frieske, J., Shardonofsky, F., Wess, J., Knoll, B.J. and Bond, R.A. Muscarinic M2 receptors modulate airway responses to methacholine in a murine model of asthma. 15th IUPHAR World Congress of Pharmacology, Beijing. 2006

Lin, R., Parra, S., Arora, V., Chan, B., Frieske, J., Syed, A., Knoll, B.J. and Bond, R.A. Potential mechanisms of the beneficial effect of chronic nadolol treatment in a murine model of asthma. 15th IUPHAR World Congress of Pharmacology, Beijing, 2006

Awwad, H. and Knoll, B.J. RNA interference of the adaptor protein complex 2 inhibits β2-adrenergic receptor internalization. Experimental Biology, San Diego, CA, 2005

Courses

  • PHAR 4301 Cellular Life Sciences II (Immunology)
  • PCOL 6363 Advanced Immunopharmacology
  • PCOL 7333 Principles of Molecular Pharmacology

Other Current Appointments

Department of Biology and Biochemistry, University of Houston, College of Natural Sciences and Mathematics (Joint)

Grant Proposal Review Groups

  • American Heart Association, Texas Affiliate, Central
    Research Review Committee, 1991-1998
  • Basic Sciences Subcommittee, Research Committee,
    Houston VA Medical Center, 1994-1996
  • American Heart Association, Western States Affiliate Peer
    Review Consortium, 1999-2002
  • Texas Advanced Research Program Biological Sciences Internal Review Committee,
    University of Houston, 2005
  • Graduate Student Research Fellowship,
    National Science Foundation, 2014-present

Editorial Appointments

Editorial Boards

  • PLoS ONE (2012-present)
  • British Journal of Pharmacology (2009-12)

Journal Referee

  • American Journal of Pathology
  • Archives of Biochemistry and Biophysics
  • Biochemical Pharmacology
  • Biochemistry
  • Biochimica et Biophysica Acta (Biomembranes)
  • British Journal of Pharmacology
  • Cancer Research
  • Endocrinology
  • Experimental Cell Research
  • Journal of Biological Chemistry
  • Journal of Cell Science
  • Journal of Cellular Physiology
  • Journal of Pharmacology and Experimental Therapeutics
  • International Journal of Biochemistry & Cell Biology
  • Life Sciences
  • Molecular Pharmacology
  • Placenta
  • PLoS One
  • Proceedings of the National Academy Science, U.S.A

Society Memberships

  • American Association of Colleges of Pharmacy
  • American Society for Pharmacology and Experimental Therapeutics
  • British Pharmacological Society