Profile: Brian Knoll

Brian Knoll
Brian J. Knoll, Ph.D.
Associate Professor of Pharmacology
Director of Graduate Education
Department of Pharmacological and Pharmaceutical Sciences
521 D Science and Research Building 2
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

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

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 6470 Advanced Pharmacology
  • 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
  • American Heart Association, Western States Affiliate Peer
    Review Consortium, 1999-2002
  • Basic Sciences Subcommittee, Research Committee,
    Houston VA Medical Center, 1994-1996

Editorial Board

  • PLoS ONE (2012-present)
  • British Journal of Pharmacology (2003-2006)

Society Memberships

  • American Society for Pharmacology and Experimental Therapeutics
  • British Pharmacological Society