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Alan Wells, D.M.Sc., M.D.
Professor and Vice-Chair, Department of Pathology, Professor, Department of Bioengineering, Executive Council, McGowan Institute for Regenerative Medicine, University of Pittsburgh Cancer Institute


Research summary: Physiological and Pathological Aspects of Cell Motility – from Molecules to Tissues.
Degrees:
M.D. in Medicine from Brown University, 1988
D.M.Sc. in Tumor Biology from Karolinska Institute, Stockholm, Sweden, 1982

Training technologies used:
Biological Imaging; Receptor Analysis; Transgenic and Gene Knock-out Animals

Departments:
Department of Pathology and Department of Bioengineering

Contact:
Scaife 713
Department of Pathology
Pittsburgh PA 15261

Phone: 412-624-0973
E-mail: wellsa@upmc.edu
Website: http://path.upmc.edu/divisions/wells-lab/wells.htm
Research interests:
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 molecular cell biological and biophysical mechanistic studies, integrated via a systems biology approach, 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 wound 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 physiological and pathological onco-fetal-wound program.
Recent publications:

Yates CC, Bodnar R, Wells A. Matrix control of scarring. Cell Mol Life Sci. 2011 Jun;68(11):1871-81. Epub 2011 Mar 10. PubMed PMID: 21390544.

Wells A, Chao YL, Grahovac J, Wu Q, Lauffenburger DA. Epithelial and mesenchymal phenotypic switchings modulate cell motility in metastasis. Front Biosci. 2011 Jan 1;16:815-37. Review. PubMed PMID: 21196205.

Bae YH, Ding Z, Das T, Wells A, Gertler F, Roy P. Profilin1 regulates PI(3,4)P2 and lamellipodin accumulation at the leading edge thus influencing motility of MDA-MB-231 cells. Proc Natl Acad Sci U S A. 2010 Dec14;107(50):21547-52. Epub 2010 Nov 29. PubMed PMID: 21115820; PubMed Central PMCID: PMC3003040.

Shao H, Wang JH, Pollak MR, Wells A. α-actinin-4 is essential for maintaining the spreading, motility and contractility of fibroblasts. PLoS One. 2010 Nov 11;5(11):e13921. PubMed PMID: 21085685; PubMed Central PMCID: PMC2978680.

Rodrigues M, Griffith LG, Wells A. Growth factor regulation of proliferation and survival of multipotential stromal cells. Stem Cell Res Ther. 2010 Oct 26;1(4):32. PubMed PMID: 20977782; PubMed Central PMCID: PMC2983445.

Krishna P, Regner M, Palko J, Liu F, Abramowitch S, Jiang J, Wells A. The effects of decorin and HGF-primed vocal fold fibroblasts in vitro and ex vivo in a porcine model of vocal fold scarring. Laryngoscope. 2010 Nov;120(11):2247-57. PubMed PMID: 20830759.

Leloup L, Shao H, Bae YH, Deasy B, Stolz D, Roy P, Wells A. m-Calpain activation is regulated by its membrane localization and by its binding to phosphatidylinositol 4,5-bisphosphate. J Biol Chem. 2010 Oct 22;285(43):33549-66. Epub 2010 Aug 20. PubMed PMID: 20729206; PubMed Central PMCID: PMC2963356.

Chao YL, Shepard CR, Wells A. Breast carcinoma cells re-express E-cadherin during mesenchymal to epithelial reverting transition. Mol Cancer. 2010 Jul 7;9:179. PubMed PMID: 20609236; PubMed Central PMCID: PMC2907333.

Hood BL, Grahovac J, Flint MS, Sun M, Charro N, Becker D, Wells A, Conrads TP. Proteomic analysis of laser microdissected melanoma cells from skin organ cultures. J Proteome Res. 2010 Jul 2;9(7):3656-63. PubMed PMID: 20459140.

Yates CC, Krishna P, Whaley D, Bodnar R, Turner T, Wells A. Lack of CXC chemokine receptor 3 signaling leads to hypertrophic and hypercellular scarring. Am J Pathol. 2010 Apr;176(4):1743-55. Epub 2010 Mar 4. PubMed PMID: 20203286; PubMed Central PMCID: PMC2843466.

Shao H, Wu C, Wells A. Phosphorylation of alpha-actinin 4 upon epidermal growth factor exposure regulates its interaction with actin. J Biol Chem. 2010 Jan 22;285(4):2591-600. Epub 2009 Nov 17. PubMed PMID: 19920151; PubMed Central PMCID: PMC2807316.

Ding Z, Gau D, Deasy B, Wells A, Roy P. Both actin and polyproline interactions of profilin-1 are required for migration, invasion and capillary morphogenesis of vascular endothelial cells. Exp Cell Res. 2009 Oct 15;315(17):2963-73. Epub 2009 Jul 14. PubMed PMID: 19607826; PubMed Central PMCID: PMC2757537.

Bodnar RJ, Yates CC, Rodgers ME, Du X, Wells A. IP-10 induces dissociation of newly formed blood vessels. J Cell Sci. 2009 Jun 15;122(Pt 12):2064-77. Epub 2009 May 26. PubMed PMID: 19470579; PubMed Central PMCID: PMC2723158.

Yates CC, Whaley D, Hooda S, Hebda PA, Bodnar RJ, Wells A. Delayed reepithelialization and basement membrane regeneration after wounding in mice lacking CXCR3. Wound Repair Regen. 2009 Jan-Feb;17(1):34-41. PubMed PMID: 19152649; PubMed Central PMCID: PMC2928121.

Bae YH, Ding Z, Zou L, Wells A, Gertler F, Roy P. Loss of profilin-1 expression enhances breast cancer cell motility by Ena/VASP proteins. J Cell Physiol. 2009 May;219(2):354-64. PubMed PMID: 19115233; PubMed Central PMCID:
PMC2990882.

Das T, Bae YH, Wells A, Roy P. Profilin-1 overexpression upregulates PTEN and suppresses AKT activation in breast cancer cells. J Cell Physiol. 2009 Feb;218(2):436-43. PubMed PMID: 18937284; PubMed Central PMCID: PMC2874249.

Yates CC, Whaley D, Y-Chen A, Kulesekaran P, Hebda PA, Wells A. ELR-negative CXC chemokine CXCL11 (IP-9/I-TAC) facilitates dermal and epidermal maturation during wound repair. Am J Pathol. 2008 Sep;173(3):643-52. Epub 2008 Jul 31. PubMed PMID: 18669615; PubMed Central PMCID: PMC2527079.

Shao H, Yi XM, Wells A. Epidermal growth factor protects fibroblasts from apoptosis via PI3 kinase and Rac signaling pathways. Wound Repair Regen. 2008 Jul-Aug;16(4):551-8. PubMed PMID: 18638274; PubMed Central PMCID: PMC2547354.

Mi Z, Holmes FA, Hellerstedt B, Pippen J, Collea R, Backner A, Bush JE, Gallion HH, Wells A, O'Shaughnessy JA. Feasibility assessment of a chemoresponse assay to predict pathologic response in neoadjuvant chemotherapy for breast cancer patients. Anticancer Res. 2008 May-Jun;28(3B):1733-40. PubMed PMID: 18630452.


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