Donna Jane Webb, Ph.D.

Associate Professor
Faculty Appointments
Associate Professor of Biological Sciences Associate Professor of Cancer Biology
Ph.D., Biochemistry, University of Virginia, Charlottesville, VirginiaB.S., Chemistry, James Madison University, Harrisonburg, Virginia
Office Address
VU Station B, Box 35-1634
Nashville, TN 37235
Research Description
My laboratory is interested in cell migration, which plays a pivotal role in many important phenomena including cancer, mental retardation and embryonic development. We are studying the signaling pathways that regulate adhesion and cytoskeletal dynamics in a variety of normal and cancer cells since this could lead to new targets for the development of anti-cancer therapeutics. A special focus in my lab is understanding the signaling pathways that regulate the formation of dendritic spines and synapses in the central nervous system. The dynamics of these spines is an exciting frontier in neuroscience because it contributes to synaptic plasticity, which underlies cognitive functions, such as learning and memory.
Research Keywords
Signal Transduction Pathways that Regulate Adhesion and Cytoskeletal Dynamics in Migration and Synapse Formation, Cell biology, Neurobiology
Gao Y, Majumdar D, Jovanovic B, Shaifer C, Lin PC, Zijlstra A, Webb DJ, Li D. A versatile valve-enabled microfluidic cell co-culture platform and demonstration of its applications to neurobiology and cancer biology. Biomed Microdevices. 2011 Jun; 13(3): 539-48. PMID: 21424383, PMCID: PMC3085600, DOI: 10.1007/s10544-011-9523-9, ISSN: 1572-8781.

Majumdar D, Gao Y, Li D, Webb DJ. Co-culture of neurons and glia in a novel microfluidic platform. J. Neurosci. Methods [print-electronic]. 2011 Mar 3/15/2011; 196(1): 38-44. PMID: 21185867, PMCID: PMC3042731, PII: S0165-0270(10)00712-0, DOI: 10.1016/j.jneumeth.2010.12.024, ISSN: 1872-678X.

Majumdar D, Nebhan CA, Hu L, Anderson B, Webb DJ. An APPL1/Akt signaling complex regulates dendritic spine and synapse formation in hippocampal neurons. Mol. Cell. Neurosci [print-electronic]. 2011 Mar; 46(3): 633-44. PMID: 21236345, PMCID: PMC3046229, PII: S1044-7431(11)00007-8, DOI: 10.1016/j.mcn.2011.01.003, ISSN: 1095-9327.

Lin WH, Nebhan CA, Anderson BR, Webb DJ. Vasodilator-stimulated phosphoprotein (VASP) induces actin assembly in dendritic spines to promote their development and potentiate synaptic strength. J. Biol. Chem [print-electronic]. 2010 Nov 11/12/2010; 285(46): 36010-20. PMID: 20826790, PMCID: PMC2975223, PII: M110.129841, DOI: 10.1074/jbc.M110.129841, ISSN: 1083-351X.

Svitkina T, Lin WH, Webb DJ, Yasuda R, Wayman GA, Van Aelst L, Soderling SH. Regulation of the postsynaptic cytoskeleton: roles in development, plasticity, and disorders. J. Neurosci. 2010 Nov 11/10/2010; 30(45): 14937-42. PMID: 21068295, PMCID: PMC3074493, PII: 30/45/14937, DOI: 10.1523/JNEUROSCI.4276-10.2010, ISSN: 1529-2401.

Gant-Branum RL, Broussard JA, Mahsut A, Webb DJ, McLean JA. Identification of phosphorylation sites within the signaling adaptor APPL1 by mass spectrometry. J. Proteome Res. 2010 Mar 3/5/2010; 9(3): 1541-8. PMID: 20095645, PMCID: PMC2845304, DOI: 10.1021/pr901043e, ISSN: 1535-3907.

Bristow JM, Sellers MH, Majumdar D, Anderson B, Hu L, Webb DJ. The Rho-family GEF Asef2 activates Rac to modulate adhesion and actin dynamics and thereby regulate cell migration. J. Cell. Sci [print-electronic]. 2009 Dec 12/15/2009; 122(Pt 24): 4535-46. PMID: 19934221, PMCID: PMC2787464, PII: jcs.053728, DOI: 10.1242/jcs.053728, ISSN: 1477-9137.

Lin WH, Webb DJ. Actin and Actin-Binding Proteins: Masters of Dendritic Spine Formation, Morphology, and Function. Open Neurosci J. 2009 Jan 1/1/2009; 3: 54-66. PMID: 20717495, PMCID: PMC2921857, DOI: 10.2174/1874082000903020054, ISSN: 1874-0820.

Wegner AM, Nebhan CA, Hu L, Majumdar D, Meier KM, Weaver AM, Webb DJ. N-wasp and the arp2/3 complex are critical regulators of actin in the development of dendritic spines and synapses. J. Biol. Chem [print-electronic]. 2008 Jun 6/6/2008; 283(23): 15912-20. PMID: 18430734, PMCID: PMC2414292, PII: M801555200, DOI: 10.1074/jbc.M801555200, ISSN: 0021-9258.

Broussard JA, Webb DJ, Kaverina I. Asymmetric focal adhesion disassembly in motile cells. Curr. Opin. Cell Biol. 2008 Feb; 20(1): 85-90. PMID: 18083360, PII: S0955-0674(07)00160-3, DOI: 10.1016/, ISSN: 0955-0674.

Webb DJ, Zhang H, Majumdar D, Horwitz AF. Alpha5 integrin signaling regulates the formation of spines and synapses in hippocampal neurons. J. Biol. Chem [print-electronic]. 2007 Mar 3/9/2007; 282(10): 6929-35. PMID: 17213186, PMCID: PMC2750863, PII: M610981200, DOI: 10.1074/jbc.M610981200, ISSN: 0021-9258.

Peacock JG, Miller A.L., Bradley W.D., Rodriguez O.C., Webb D.J., and Koleske A.J.. The Abl-Related Gene Tyrosine Kinase Acts through p190RhoGAP to Inhibit Actomyosin Contractility and Regulate Focal Adhesion Dynamics upon Adhesion to Fibronectin. Mol. Biol. Cell. 2007; 18: 3860-72.

Mayhew MW, Webb DJ, Kovalenko M, Whitmore L, Fox JW, Horwitz AF. Identification of protein networks associated with the PAK1-betaPIX-GIT1-paxillin signaling complex by mass spectrometry. J. Proteome Res. 2006 Sep; 5(9): 2417-23. PMID: 16944954, DOI: 10.1021/pr060140t, ISSN: 1535-3893.

Webb DJ, Kovalenko M, Whitmore L, Horwitz AF. Phosphorylation of serine 709 in GIT1 regulates protrusive activity in cells. Biochem. Biophys. Res. Commun [print-electronic]. 2006 Aug 8/11/2006; 346(4): 1284-8. PMID: 16797488, PII: S0006-291X(06)01341-6, DOI: 10.1016/j.bbrc.2006.06.036, ISSN: 0006-291X.

Webb DJ, Mayhew MW, Kovalenko M, Schroeder MJ, Jeffery ED, Whitmore L, Shabanowitz J, Hunt DF, Horwitz AF. Identification of phosphorylation sites in GIT1. J. Cell. Sci. 2006 Jul 7/15/2006; 119(Pt 14): 2847-50. PMID: 16825424, PII: 119/14/2847, DOI: 10.1242/jcs03044, ISSN: 0021-9533.

Lieu AS, Li JZ, Webb DJ, Hankins GR, Howng SL, Helm GA. Functions of G protein-coupled receptor kinase interacting protein 1 in human neuronal (NT2N) cells. J. Neurosurg. 2006 Jul; 105(1): 103-10. PMID: 16871884, DOI: 10.3171/jns.2006.105.1.103, ISSN: 0022-3085.

Nayal A, Webb DJ, Brown CM, Schaefer EM, Vicente-Manzanares M, Horwitz AR. Paxillin phosphorylation at Ser273 localizes a GIT1-PIX-PAK complex and regulates adhesion and protrusion dynamics. J. Cell Biol. 2006 May 5/22/2006; 173(4): 587-9. PMID: 16717130, PMCID: PMC2063867, PII: jcb.200509075, DOI: 10.1083/jcb.200509075, ISSN: 0021-9525.

Vicente-Manzanares M, Webb DJ, Horwitz AR. Cell migration at a glance. J. Cell. Sci. 2005 Nov 11/1/2005; 118(Pt 21): 4917-9. PMID: 16254237, PII: 118/21/4917, DOI: 10.1242/jcs.02662, ISSN: 0021-9533.

Webb DJ, Schroeder MJ, Brame CJ, Whitmore L, Shabanowitz J, Hunt DF, Horwitz AR. Paxillin phosphorylation sites mapped by mass spectrometry. J. Cell. Sci. 2005 Nov 11/1/2005; 118(Pt 21): 4925-9. PMID: 16254239, PII: 118/21/4925, DOI: 10.1242/jcs.02563, ISSN: 0021-9533.

Schroeder MJ, Webb DJ, Shabanowitz J, Horwitz AF, Hunt DF. Methods for the detection of paxillin post-translational modifications and interacting proteins by mass spectrometry. J. Proteome Res. 2005 Sep; 4(5): 1832-41. PMID: 16212439, DOI: 10.1021/pr0502020, ISSN: 1535-3893.

Bryce NS, Clark ES, Leysath JL, Currie JD, Webb DJ, Weaver AM. Cortactin promotes cell motility by enhancing lamellipodial persistence. Curr. Biol. 2005 Jul 7/26/2005; 15(14): 1276-85. PMID: 16051170, PII: S0960-9822(05)00678-0, DOI: 10.1016/j.cub.2005.06.043, ISSN: 0960-9822.

Zhang H, Webb DJ, Asmussen H, Niu S, Horwitz AF. A GIT1/PIX/Rac/PAK signaling module regulates spine morphogenesis and synapse formation through MLC. J. Neurosci. 2005 Mar 3/30/2005; 25(13): 3379-88. PMID: 15800193, PII: 25/13/3379, DOI: 10.1523/JNEUROSCI.3553-04.2005, ISSN: 1529-2401.

Webb DJ, Zhang H, Horwitz AF. Cell migration: an overview. Methods Mol. Biol. 2005; 294: 3-11. PMID: 15576900, PII: 1-59259-860-9:003, ISSN: 1064-3745.

Wiseman PW, Brown CM, Webb DJ, Hebert B, Johnson NL, Squier JA, Ellisman MH, Horwitz AF. Spatial mapping of integrin interactions and dynamics during cell migration by image correlation microscopy. J. Cell. Sci [print-electronic]. 2004 Nov 11/1/2004; 117(Pt 23): 5521-34. PMID: 15479718, PII: jcs.01416, DOI: 10.1242/jcs.01416, ISSN: 0021-9533.

Webb DJ, Donais K, Whitmore LA, Thomas SM, Turner CE, Parsons JT, Horwitz AF. FAK-Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly. Nat. Cell Biol [print-electronic]. 2004 Feb; 6(2): 154-61. PMID: 14743221, PII: ncb1094, DOI: 10.1038/ncb1094, ISSN: 1465-7392.

Nayal A, Webb DJ, Horwitz AF. Talin: an emerging focal point of adhesion dynamics. Curr. Opin. Cell Biol. 2004 Feb; 16(1): 94-8. PMID: 15037311, PII: S0955067403001650, DOI: 10.1016/, ISSN: 0955-0674.

Webb DJ, Brown CM, Horwitz AF. Illuminating adhesion complexes in migrating cells: moving toward a bright future. Curr. Opin. Cell Biol. 2003 Oct; 15(5): 614-20. PMID: 14519397, PII: S0955067403001054, ISSN: 0955-0674.

Webb DJ, Horwitz AF. New dimensions in cell migration. Nature cell biology. 2003 Aug; 5(8) Sect. 690,2.

Zhang H, Webb DJ, Asmussen H, Horwitz AF. Synapse formation is regulated by the signaling adaptor GIT1. J. Cell Biol. 2003 Apr 4/14/2003; 161(1): 131-42. PMID: 12695502, PMCID: PMC2172873, PII: jcb.200211002, DOI: 10.1083/jcb.200211002, ISSN: 0021-9525.

Ma Z, Thomas KS, Webb DJ, Moravec R, Salicioni AM, Mars WM, Gonias SL. Regulation of Rac1 activation by the low density lipoprotein receptor-related protein. J. Cell Biol [print-electronic]. 2002 Dec 12/23/2002; 159(6): 1061-70. PMID: 12499359, PMCID: PMC2173989, PII: jcb.200207070, DOI: 10.1083/jcb.200207070, ISSN: 0021-9525.

Corbin JD, Francis SH, Webb DJ. Phosphodiesterase type 5 as a pharmacologic target in erectile dysfunction. Urology. 2002 Sep; 60(2 Suppl 2): 4-11. PMID: 12414329, PII: S0090429502016862, ISSN: 1527-9995.

Mettenburg JM, Webb DJ, Gonias SL. Distinct binding sites in the structure of alpha 2-macroglobulin mediate the interaction with beta-amyloid peptide and growth factors. J. Biol. Chem [print-electronic]. 2002 Apr 4/12/2002; 277(15): 13338-45. PMID: 11823454, PII: M106792200, DOI: 10.1074/jbc.M106792200, ISSN: 0021-9258.

Webb DJ, Parsons JT, Horwitz AF. Adhesion assembly, disassembly and turnover in migrating cells -- over and over and over again. Nat. Cell Biol. 2002 Apr; 4(4): E97-100. PMID: 11944043, PII: ncb0402-e97, DOI: 10.1038/ncb0402-e97, ISSN: 1465-7392.

Manabe R, Kovalenko M, Webb DJ, Horwitz AR. GIT1 functions in a motile, multi-molecular signaling complex that regulates protrusive activity and cell migration. J. Cell. Sci. 2002 Apr 4/1/2002; 115(Pt 7): 1497-510. PMID: 11896197, ISSN: 0021-9533.

Webb DJ, Asmussen H, Murase S, Horwitz AF. Cell migration in slice cultures. Methods Cell Biol. 2002; 69: 341-58. PMID: 12071004, ISSN: 0091-679X.

Ma Z, Webb DJ, Jo M, Gonias SL. Endogenously produced urokinase-type plasminogen activator is a major determinant of the basal level of activated ERK/MAP kinase and prevents apoptosis in MDA-MB-231 breast cancer cells. J. Cell. Sci. 2001 Sep; 114(Pt 18): 3387-96. PMID: 11591826, ISSN: 0021-9533.

Laukaitis CM, Webb DJ, Donais K, Horwitz AF. Differential dynamics of alpha 5 integrin, paxillin, and alpha-actinin during formation and disassembly of adhesions in migrating cells. J. Cell Biol. 2001 Jun 6/25/2001; 153(7): 1427-40. PMID: 11425873, PMCID: PMC2150721, ISSN: 0021-9525.

Webb DJ, Thomas KS, Gonias SL. Plasminogen activator inhibitor 1 functions as a urokinase response modifier at the level of cell signaling and thereby promotes MCF-7 cell growth. J. Cell Biol. 2001 Feb 2/19/2001; 152(4): 741-52. PMID: 11266465, PMCID: PMC2195772, ISSN: 0021-9525.

Webb DJ, Roadcap DW, Dhakephalkar A, Gonias SL. A 16-amino acid peptide from human alpha2-macroglobulin binds transforming growth factor-beta and platelet-derived growth factor-BB. Protein Sci. 2000 Oct; 9(10): 1986-92. PMID: 11106172, PMCID: PMC2144455, DOI: 10.1110/ps.9.10.1986, ISSN: 0961-8368.

Nguyen DH, Webb DJ, Catling AD, Song Q, Dhakephalkar A, Weber MJ, Ravichandran KS, Gonias SL. Urokinase-type plasminogen activator stimulates the Ras/Extracellular signal-regulated kinase (ERK) signaling pathway and MCF-7 cell migration by a mechanism that requires focal adhesion kinase, Src, and Shc. Rapid dissociation of GRB2/Sps-Shc complex is associated with the transient phosphorylation of ERK in urokinase-treated cells. J. Biol. Chem. 2000 Jun 6/23/2000; 275(25): 19382-8. PMID: 10777511, PII: M909575199, DOI: 10.1074/jbc.M909575199, ISSN: 0021-9258.

Gonias SL, Carmichael A, Mettenburg JM, Roadcap DW, Irvin WP, Webb DJ. Identical or overlapping sequences in the primary structure of human alpha(2)-macroglobulin are responsible for the binding of nerve growth factor-beta, platelet-derived growth factor-BB, and transforming growth factor-beta. J. Biol. Chem. 2000 Feb 2/25/2000; 275(8): 5826-31. PMID: 10681572, ISSN: 0021-9258.

Garber TR, Gonias SL, Webb DJ. Interleukin-4 and IL-10 bind covalently to activated human alpha2-macroglobulin by a mechanism that requires Cys949. J. Interferon Cytokine Res. 2000 Feb; 20(2): 125-31. PMID: 10714547, DOI: 10.1089/107999000312522, ISSN: 1079-9907.

Webb DJ, Nguyen DH, Gonias SL. Extracellular signal-regulated kinase functions in the urokinase receptor-dependent pathway by which neutralization of low density lipoprotein receptor-related protein promotes fibrosarcoma cell migration and matrigel invasion. J. Cell. Sci. 2000 Jan; 113 ( Pt 1): 123-34. PMID: 10591631, ISSN: 0021-9533.

Nguyen DH, Catling AD, Webb DJ, Sankovic M, Walker LA, Somlyo AV, Weber MJ, Gonias SL. Myosin light chain kinase functions downstream of Ras/ERK to promote migration of urokinase-type plasminogen activator-stimulated cells in an integrin-selective manner. J. Cell Biol. 1999 Jul 7/12/1999; 146(1): 149-64. PMID: 10402467, PMCID: PMC2199739, ISSN: 0021-9525.

Webb DJ, Nguyen DH, Sankovic M, Gonias SL. The very low density lipoprotein receptor regulates urokinase receptor catabolism and breast cancer cell motility in vitro. J. Biol. Chem. 1999 Mar 3/12/1999; 274(11): 7412-20. PMID: 10066806, ISSN: 0021-9258.

Kralovich KR, Li L, Hembrough TA, Webb DJ, Karns LR, Gonias SL. Characterization of the binding sites for plasminogen and tissue-type plasminogen activator in cytokeratin 8 and cytokeratin 18. J. Protein Chem. 1998 Nov; 17(8): 845-54. PMID: 9988531, ISSN: 0277-8033.

Webb DJ, Gonias SL. A modified human alpha 2-macroglobulin derivative that binds tumor necrosis factor-alpha and interleukin-1 beta with high affinity in vitro and reverses lipopolysaccharide toxicity in vivo in mice. Lab. Invest. 1998 Aug; 78(8): 939-48. PMID: 9714181, ISSN: 0023-6837.

Webb DJ, Wen J, Karns LR, Kurilla MG, Gonias SL. Localization of the binding site for transforming growth factor-beta in human alpha2-macroglobulin to a 20-kDa peptide that also contains the bait region. J. Biol. Chem. 1998 May 5/22/1998; 273(21): 13339-46. PMID: 9582381, ISSN: 0021-9258.

Webb DJ, Gonias SL. Chemical modification of alpha2-macroglobulin to generate derivatives that bind transforming growth factor-beta with increased affinity. FEBS Lett. 1997 Jun 6/30/1997; 410(2-3): 249-53. PMID: 9237639, PII: S0014-5793(97)00598-X, ISSN: 0014-5793.

Webb DJ, Weaver AM, Atkins-Brady TL, Gonias SL. Proteinases are isoform-specific regulators of the binding of transforming growth factor beta to alpha 2-macroglobulin. Biochem. J. 1996 Dec 12/1/1996; 320 ( Pt 2): 551-5. PMID: 8973565, PMCID: PMC1217964, ISSN: 0264-6021.

Webb DJ, Wen J, Lysiak JJ, Umans L, Van Leuven F, Gonias SL. Murine alpha-macroglobulins demonstrate divergent activities as neutralizers of transforming growth factor-beta and as inducers of nitric oxide synthesis. A possible mechanism for the endotoxin insensitivity of the alpha2-macroglobulin gene knock-out mouse. J. Biol. Chem. 1996 Oct 10/4/1996; 271(40): 24982-8. PMID: 8798779, ISSN: 0021-9258.

Webb DJ, Hussaini IM, Weaver AM, Atkins TL, Chu CT, Pizzo SV, Owens GK, Gonias SL. Activated alpha 2-macroglobulin promotes mitogenesis in rat vascular smooth muscle cells by a mechanism that is independent of growth-factor-carrier activity. Eur. J. Biochem. 1995 Dec 12/15/1995; 234(3): 714-22. PMID: 8575427, ISSN: 0014-2956.

Webb DJ, Crookston KP, Figler NL, Lamarre J, Gonias SL. Differences in the binding of transforming growth factor beta 1 to the acute-phase reactant and constitutively synthesized alpha-macroglobulins of rat. Biochem. J. 1995 Dec 12/1/1995; 312 ( Pt 2): 579-86. PMID: 8526873, PMCID: PMC1136301, ISSN: 0264-6021.

Lysiak JJ, Hussaini IM, Webb DJ, Glass WF, Allietta M, Gonias SL. Alpha 2-macroglobulin functions as a cytokine carrier to induce nitric oxide synthesis and cause nitric oxide-dependent cytotoxicity in the RAW 264.7 macrophage cell line. J. Biol. Chem. 1995 Sep 9/15/1995; 270(37): 21919-27. PMID: 7545171, ISSN: 0021-9258.

Available Postdoctoral Position Details
Posted: 6/8/2011
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