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Research Interests:
Dr. Wells' laboratory research program, in close collaboration with its research partners, aims to understand cell migration in terms of how motility processes are regulated, and understand how this regulation of migration plays a role in physiologic and pathologic situations. We are integrating the knowledge gained from our biochemical and biophysical mechanistic studies into our investigations concerning conditions of dysregulated (tumor invasion) and orchestrated (wound healing and organogenesis) cell motility. As part of understanding the motility response, we are investigating both how this particular integrated cell response is selected from among others and the metabolic consequences of motility. This integrative approach provides reinforcing insights and novel avenues for exploration into the basic signaling pathways as well as functioning of whole organism. As a model system, we explore motility signaling from the epidermal growth factor receptor (EGFR) in adherent cells. EGFR plays a central role in the functioning in a wide variety of both stromal and epithelial tissues, and is the prototype for other receptors with intrinsic tyrosine kinase activity. Thus, these studies should have widespread implications.
Selected Publications:
A Glading, R Bodnar, IJ Reynolds, H Shiraha, L Satish, DA Potter, HC Blair, A Wells (2004). EGF activates m-calpain (calpain 2), at least in part, by ERK-mediated phosphorylation. Molecular and Cellular Biology 24, 2499-2512.
A Iwabu, K Smith, FD Allen, DA Lauffenburger, A Wells (2004). EGF induces fibroblast contractility and motility via a PKC -dependent pathway. Journal of Biological Chemistry 279, 14551-14560.
A Mamoune, J Kassis, S Kharait, S Kloecker, E Manos, DA Jones, A Wells (2004). DU145 human prostate carcinoma invasiveness is modulated by urokinase receptor (uPAR) downstream of epidermal growth factor receptor (EGFR) signaling. Experimental Cell Research 299, 91-100.
A Wells, L Lillien (2004). Attraction or repulsion: a matter of individual taste? Science STKE 2004, pe47.
C Yates, A Wells, T Turner (2005). Luteinizing hormone releasing hormone (LHRH) analog reverses the cell adhesion profile of EGFR overexpressing DU-145 human prostate carcinoma subline. British Journal of Cancer 92, 366-375.
L Satish, HC Blair, A Glading, A Wells (2005). IP-9 (CXCL11) induced cell motility in keratinocytes requires calcium flux-dependent activation of -calpain. Molecular and Cellular Biology 25, 1922-1941.
S Hauteniemi, S Kharait, A Iwabu, A Wells, DA Lauffenburger (2005). Modeling and prediction of signal transduction cascades using decision trees. Bioinformatics 21, 2027-2035.
A Wells, ed (2005). Cell Motility in Cancer Invasion and Metastasis, Kluwer Academic Press.
C Yates, CR Shepard, G Papworth, A Dash, DB Stolz, S Tannenbaum, L Griffith, A Wells (2006). Novel three-dimensional organotypic liver bioreactor to directly visualize early events in metastatic progression. Advances in Cancer Research, in press.
K Tamama, VH Fan, LG Griffith, HC Blair, A Wells (2006). Epidermal growth factor as candidate for ex vivo expansion of bone marrow-derived mesenchymal stem cells. Stem Cells 24, 686-695.
R Bodnar, C Yates, A Wells (2006). IP-10 blocks VEGF-induced endothelial cell motility and tube formation via inhibition of calpain. Circulation Research 98, 617-625.
BR Smith, A Wells, CB Alexander, S Campbell, A Dasgupta, M Fung, B Haller, JG Howe, C Parvin, E Peerschke, H Rinder, S Spitalnik, R Weiss, M Wener (2006). Curriculum content and evaluation of resident competency in Clinical Pathology (Laboratory Medicine): a proposal. Multiple coordinated publications in: Clinical Chemistry 52, 917-949. Pathology Patterns 125, S1-37. Human Pathology, in press.
R Babu, J Zhang, EJ Beckman, M Virji, WA Pasculle, A Wells (2006). Antimicrobial activities of silver used as a polymerization catalyst for a wound healing matrix. Biomaterials 27, 4304-4314.
H Shao, J Chou, CJ Batey, NA Burke, SC Watkins, DB Stolz, A Wells (2006). Spatial localization of m-calpain to the plasma membrane by PIP2 binding during EGF receptor-mediated activation. Molecular and Cellular Biology 26, 5481-5496.
MH Zaman, LM Trapani, A Siemeski, D McKeller, H Gong, RD Kamm, A Wells, DA Lauffenburger, P Matsudaira (2006). Migration of tumor cells in three-dimensional matrices is governed by matrix stiffness along with cell-matrix adhesion and proteolysis. Proceedings of the National Academy of Sciences (USA) 103, 10889-10894.
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