Alan Wells, MD DMS
Professor of Pathology
The 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.
The two central foci are tumor progression and wound repair. In tumor progression, we examine breast and prostate carcinoma invasion and metastases in terms of molecular signals and the special micro-environments. For this, the laboratory uses human tissues, animal models, and a unique 4-dimensional liver microtissue. In would repair, the current model system is skin wound healing, in which the communications between the epidermis, dermis, and blood vessels is parsed at the molecular levels. The role of stem cells in the natural repair process and as a rationale therapeutic is also being investigated. These two areas are re-inforcing as many of the key molecules and cellular processes are part of the generalizable onco-fetal-wound program.
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For details of current projects, publications and members of the Wells Lab please see: http://www.path.upmc.edu/divisions/wells-lab/wells.htm
Recent Publication
View Dr. Wells' publications on PubMed.
Primary Articles:
CC Yates, D Whaley, S Hooda, PA Hebda, RJ Bodnar, A Wells (2009). Delayed re-epithelialization and basement membrane regeneration after wounding in mice lacking CXCR3. Wound Repair and Regeneration 17, 34-41. PMID: 19152649
RJ Bodnar, CC Yates, M Rodgers, X Du, A Wells (2009). IP-10 induces dissociation of newly formed vessels. Journal of Cell Science 122, 2064-2077. PMID: 19470579. PMC2723158
MO Platt, AJ Roman, A Wells, DA Lauffenburger, LG Griffith (2009). Sustained epidermal growth factor levels and activation by tethered ligand binding enhances osteogenic differentiation of multi-potent marrow stromal cells. Journal of Cellular Physiology 221, 306-317. PMID: 19544388.
MO Platt, CL Wilder, A Wells, LG Griffith, DA Lauffenburger (2009). Multi-pathway kinase signatures of multipotential stromal cells are predictive for osteogenic differentiation: tissue-specific stem cells. Stem Cells 27, 2804-2814. PMID: 19750537.
CC Yates, P Krishna, D Whaley, R Bodnar, T Turner, A Wells (2010). Lack of CXC chemokine receptor 3 (CXCR3) signaling leads to hypertrophic and hypercellular scarring. American Journal of Pathology 176, 1743-1755. PMID: 20203286. PMCID: PMC2843466
H Shao, C Wu, A Wells (2010). Phosphorylation of -actinin-4 upon epidermal growth factor (EGF) exposure regulates its interaction with actin. Journal of Biological Chemistry 285, 2591-2600. PMID: 19920151. PMC2807316.
M Li, JM Aliotta, JM Asara, Q Wu, LD Tucker, A Wells, PJ Queensberry, B Ramratnam (2010). Intercellular transfer of proteins as identified by stable isotope labeling of amino acids in cell culture. Journal of Biological Chemistry 285, 6285-6297. PMID: 20026604. PMCID: PMC2825424.
BL Hood, J Grahovac, MS Flint, M Sun, N Charro, D Becker, A Wells, TP Conrads (2010). Proteomic analysis of laser microdissected melanoma cells from skin organ cultures. Journal of Proteome Research 9, 3656-3663. PMID: 20459140. PMCID: NIHMS209402
YL Chao, CR Shepard, A Wells (2010). Breast carcinoma cells re-express E-cadherin during mesenchymal to epithelial reverting transition. Molecular Cancer 9, 179. PMID: 20609236. PMC2907333.
L Leloup, H Shao, Y-H Bae, B Deasy, D Stolz, P Roy, A Wells (2010). M-Calpain activation is regulated by its membrane localization and by its binding to PIP2. Journal of Biological Chemistry 285, 33549-33566. PMID: 20729206. PMC2963356.
H Shao, J-C Wang, MR Pollak, A Wells (2010). -Actinin-4 is essential for maintaining the spreading, motility, and contractility of fibroblasts. PLoS One 5, e13291. PMID: 21085685. PMC2978680
YH Bae, Z Ding, T Das, A Wells, F Gertler, P Roy (2010). Profilin-1 regulates PI(3,4)P2 and lamellipodin accumulation at the leading edge thus influencing MDA-MB-231 cell motility. Proceedings of the National Academy of Sciences (USA) 107, 21547-21552. PMID: 21115820. PMC3003040.
S Wu, A Wells, L Griffith, DA Lauffenburger (2011). Controlling multipotential stromal cell migration by integrating "coarse-graining" materials and "fine-tuning" small molecules via decision tree signal-response modeling. Biomaterials 32, 7524-7531. PMID: 21782235.
C Yates, DL Whaley, A Wells (2011). Transplanted fibroblasts prevent dysfunctional repair in a murine CXCR3-deficient scarring model. Cell Transplantation, in press.
YL Chao, Q Wu, M Acquafondata, R Dhir, A Wells (2011). Partial mesenchymal to epithelial reverting transition in breast and prostate cancer metastases. Cancer Microenvironment, in press.
HD Kim, AS Meyer, JP Wagner, SK Alford, A Wells, FB Gertler, DA Lauffenburger (2011). Signaling network state predicts Twist-mediated effects on breast cell migration across diverse growth factor contexts. Molecular and Cellular Proteomics, in press.
YL Chao, Q Wu, C Shepard, A Wells (2011). Hepatocyte-induced re-expression of E-cadherin in breast and prostate cancer cells increases chemoresistance. Clinical and Experimental Metastasis, in press.
Reviews:
M Rodrigues, LG Griffith, A Wells (2010). Growth factor regulation of proliferation and survival of MSC. Stem Cell Research and Therapy 1, 32.
A Wells, YL Chao, Q Wu (2010). Biology of metastatic liver tumors. In Molecular Pathology of Liver Diseases (Ed: PSP Monga, Springer).
A Wells, YL Chao, J Grahovac, Q Wu, DA Lauffenburger (2011). Cell motility in carcinoma metastasis as modulated by switching between epithelial and mesenchymal phenotypes. Frontiers in Bioscience 16, 815-837. PMID: 21196205.
L Leloup, A Wells (2011). Calpains as potential anti-cancer targets. Expert Opinion on Therapeutic Targets 15, 309-323. PMID: 21244345.
CC Yates, R Bodnar, A Wells (2011). Matrix control of scarring. Cellular and Molecular Life Sciences 68, 1861-1871. PMID: 21390544
