Donna J. Webb, Ph.D.
Assistant Professor of Biological Sciences
Assistant Professor of Cancer Biology
Vanderbilt University Medical Center
U6211 MRBIII, 465 21st Av S.
Nashville, TN 37232
Signal Transduction Pathways that Regulate Adhesion and Cytoskeletal Dynamics in Migration and Synapse Formation, Cell biology, Neurobiology
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.
- 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, 13(3), 539-48, 2011.
- 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, 46(3), 633-44, 2011.
- Majumdar, D, Gao, Y, Li, D, Webb, DJ Co-culture of neurons and glia in a novel microfluidic platform. J Neurosci Methods, 196(1), 38-44, 2011.
- 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, 9(3), 1541-8, 2010.
- 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, 30(45), 14937-42, 2010.
- 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, 285(46), 36010-20, 2010.
- Lin, WH, Webb, DJ Actin and Actin-Binding Proteins: Masters of Dendritic Spine Formation, Morphology, and Function. Open Neurosci J, 354-66, 2009.
- 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, 122(Pt 24), 4535-46, 2009.
- Broussard, JA, Webb, DJ, Kaverina, I Asymmetric focal adhesion disassembly in motile cells. Curr Opin Cell Biol, 20(1), 85-90, 2008.
- 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, 2008.
- 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. , 183860-3872, 2007.
- Webb, DJ, Zhang, H, Majumdar, D, Horwitz, AF alpha 5 integrin signaling regulates the formation of spines and synapses in hippocampal neurons. J Biol Chem, 2826929-6935, 2007.
- 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, 105(1), 103-10, 2006.
- 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, 119(Pt 14), 2847-50, 2006.
- 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, 5(9), 2417-23, 2006.
- 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, 173(4), 587-9, 2006.
- Webb, DJ, Kovalenko, M, Whitmore, L, Horwitz, AF Phosphorylation of serine 709 in GIT1 regulates protrusive activity in cells. Biochem Biophys Res Commun, 346(4), 1284-8, 2006.
- 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, 25(13), 3379-88, 2005.
- Vicente-Manzanares, M, Webb, DJ, Horwitz, AR Cell migration at a glance. J Cell Sci, 118(Pt 21), 4917-9, 2005.
- Webb, DJ, Zhang, H, Horwitz, AF Cell migration: an overview. Methods Mol Biol, 2943-11, 2005.
- Bryce, NS, Clark, ES, Leysath, JL, Currie, JD, Webb, DJ, Weaver, AM Cortactin promotes cell motility by enhancing lamellipodial persistence. Curr Biol, 15(14), 1276-85, 2005.
- 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, 4(5), 1832-41, 2005.
- Webb, DJ, Schroeder, MJ, Brame, CJ, Whitmore, L, Shabanowitz, J, Hunt, DF, Horwitz, AR Paxillin phosphorylation sites mapped by mass spectrometry. J Cell Sci, 118(Pt 21), 4925-9, 2005.
- 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, 6(2), 154-61, 2004.
- 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, 117(Pt 23), 5521-34, 2004.
- Nayal, A, Webb, DJ, Horwitz, AF Talin: an emerging focal point of adhesion dynamics. Curr Opin Cell Biol, 16(1), 94-8, 2004.
- Webb, DJ, Brown, CM, Horwitz, AF Illuminating adhesion complexes in migrating cells: moving toward a bright future. Curr Opin Cell Biol, 15(5), 614-20, 2003.
- Webb, DJ, Horwitz, AF New dimensions in cell migration. Nat Cell Biol, 5(8), 690-2, 2003.
- Zhang, H, Webb, DJ, Asmussen, H, Horwitz, AF Synapse formation is regulated by the signaling adaptor GIT1. J Cell Biol, 161(1), 131-42, 2003.
- Webb, DJ, Parsons, JT, Horwitz, AF Adhesion assembly, disassembly and turnover in migrating cells -- over and over and over again. Nat Cell Biol, 4(4), E97-100, 2002.
- Webb, DJ, Asmussen, H, Murase, S, Horwitz, AF Cell migration in slice cultures. Methods Cell Biol, 69341-58, 2002.
- 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, 277(15), 13338-45, 2002.
- 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, 115(Pt 7), 1497-510, 2002.
- 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, 159(6), 1061-70, 2002.
- 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, 153(7), 1427-40, 2001.
- 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, 114(Pt 18), 3387-96, 2001.
- 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, 152(4), 741-52, 2001.
- 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, 9(10), 1986-92, 2000.
- 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, 113 ( Pt 1)123-34, 2000.
- 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, 275(8), 5826-31, 2000.
- 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, 20(2), 125-31, 2000.
- 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, 275(25), 19382-8, 2000.
- 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, 146(1), 149-64, 1999.
- 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, 274(11), 7412-20, 1999.
- 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, 78(8), 939-48, 1998.
- 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, 17(8), 845-54, 1998.
- 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, 273(21), 13339-46, 1998.