Alan Wells

Scaife 713
Department of Pathology
University of Pittsburgh
Pittsburgh, PA 15261
412-624-0973/647-7813

wellsa@msx.upmc.edu

Education

Positions

1983-84 Visiting Scientist, Okayama University Medical School, Okayama, Japan
1988 Visiting Medical Scientist, Armauer Hansen Research Institute, Ethiopia
1991-97 Assistant Professor, Department of Pathology, University of Alabama at Birmingham
1991-97 Associate Scientist, Comprehensive Cancer Center, UAB
1991-99 Medical Director, Diagnostic Molecular Biology Laboratory, UAB Hospital, Birmingham
1992-99 Staff Pathologist, Veterans Administration Medical Center, Birmingham, AL
1994-99 Associate Scientist, UAB Center for Aging, University of Alabama at Birmingham
1994-99 Associate Scientist, UAB Cell and Adhesion Matrix Research Center, UAB
1997-99 Associate Professor, Department of Pathology, University of Alabama at Birmingham
1997-99 Scientist, Comprehensive Cancer Center, UAB
1999 Visiting Scientist, Laboratory for Molecular Cell Biology, University College London
1999- Adjunct Associate Professor,  Department of Pathology, University of Alabama at Birmingham
1999- Thomas J Gill III Professor, Department of Pathology, University of Pittsburgh
1999- Vice-Chair for Laboratory Medicine, Department of Pathology, University of Pittsburgh
1999- Medical Director, CSLI, University of Pittsburgh Medical Center (UPMC), Pittsburgh
1999- Staff Pathologist, Veterans Administration Medical Center, Pittsburgh, PA
2002- Executive Council, McGowan Institute for Regenerative Medicine, Pittsburgh, PA

Publications

2. N Koide, A Wells, D Volsky, I Shapiro, G Klein (1981). The detection of Epstein-Barr virus receptors utilizing radiolabelled virus. Journal of General Virology 54, 191-195. 

3. A Wells, HB Steen, S Saeland, T Godal, G Klein (1981). A microassay for quantitatively detecting the Epstein-Barr virus receptor on single cells utilizing flow cytometry. Journal of Virological Methods 3, 127-136. 

4. A Wells, HB Steen, T Godal, G Klein (1981). Epstein-Barr virus receptor expression is correlated to cell cycle phase. Journal of Receptor Research 2, 285-298. 

5. N Koide, A Wells, G Klein, I Ernberg (1981). Cell surface glycoprotein patterns of two EBV-negative lines and their EBV-converted sublines. Intervirology 16, 142-148. 

6. A Wells, N Koide, G Klein (1982). Two large virion envelope glycoproteins mediate Epstein-Barr virus binding to receptor-positive cells. Journal of Virology 41, 286-297. 

7. A Wells, T Godal, S Kvaloy, HB Steen, G Klein (1982). Quantitative comparison of Epstein-Barr virus receptor expression on sIgM and sIgG cell lines and B-cell lymphoma biopsies. Differentiation 22, 113-119. 

8. V Jonsson, A Wells, G Klein (1982). Receptors for the complement C3d component and the Epstein-Barr virus are quantitatively co-expressed on a series of B-cell lines and their derived somatic cell hybrids. Cellular Immunology 72, 263-276. 

9. A Wells, N Koide, H Stein, J Gerdes, G Klein (1983). The Epstein-Barr virus receptor is distinct from the C3 receptor. Journal of General Virology 64, 449-453. 

10. A Wells, N Koide, G Eggertsen, A Lundwall, T Godal, HB Steen,G Klein (1984). Epstein-Barr virus binding to virus-carrying cell lines is enhanced in the presence of C3 and C3d. Journal of General Virology 65, 507-513. 

11. A Wells, JM Bishop, D Helmeste (1988). Amplified gene for EGF receptor in a human glioblastoma cell line presenting an enzymatically inactive protein. Molecular and Cellular Biology 8, 4561-4565. 

12. A Wells, JM Bishop (1988). Genetic determinants of neoplastic transformation by the retroviral oncogene v-erb-B. Proceedings of the National Academy of Sciences (USA) 85, 7597-7601. 

13. A Wells, JB Welsh, CS Lazar, HS Wiley, GN Gill, MG Rosenfeld (1990). Ligand-induced transformation by a non-internalizing EGF receptor. Science 247, 962-964. 

14. U Marti, SJ Burwen, A Wells, ME Barker, S Huling, AM Feren, AL Jones (1991). Localization of epidermal growth factor receptor in hepatocyte nuclei. Hepatology 13, 15-20. 

15. JB Welsh, GN Gill, MG Rosenfeld, A Wells (1991). A negative feedback loop attenuates EGF-induced morphological changes. Journal of Cell Biology 114, 533-543. 

16. H Masui, A Wells, CS Lazar, MG Rosenfeld, GN Gill (1991). Enhanced tumorigenesis of NR6 cells which express non-downregulating epidermal growth factor receptors. Cancer Research 51, 6170-6175. 

17. C-P Chang, JP-Y Kao, CS Lazar, BJ Walsh, A Wells, HS Wiley, MG Rosenfeld, GN Gill (1991). Ligand-induced internalization and calcium mobilization require distinct carboxy terminal regions of the EGF receptor. Journal of Biological Chemistry 266, 23467-23470. 

18. P Chen, K Gupta, A Wells (1994). Cell movement elicited by epidermal growth factor receptor requires kinase and autophosphorylation but is separable from mitogenesis. Journal of Cell Biology 124, 547-555. 

19. CC Reddy, A Wells, DA Lauffenburger (1994). Proliferative response of fibroblasts expressing internalization- deficient EGF receptors is altered via differential EGF depletion effects. Biotechnology Progress 10, 377-384. 

20. P Chen, H Xie, MC Sekar, K Gupta, A Wells (1994). Epidermal growth factor receptor-mediated cell motility: Phospholipase C activity is required, but MAP kinase activity is not sufficient for induced cell motility. Journal of Cell Biology 127, 847-857. 

21. R Hardy, KB Gupta, JM. McDonald, J Williford, A Wells (1995) EGF receptor carboxy-terminal domains are required for EGF-induced glucose transport in transgenic 3T3-L1 adipocytes. Endocrinology 136, 431-439. 

22. BW Hughes, A Wells, Z Bebok, VK Gadi, RI Garver, WB Parker, EJ Sorscher (1995). Sensitization and high level bystander killing of melanoma cells using the human tyrosinase promoter to express the E. coli purine nucleoside phosphorylase gene. Cancer Research 55, 3339-3345. 

23. H Xie, T Turner, M-H Wang, RK Singh, GP Siegal, A Wells (1995). Prostate carcinoma cell, DU-145, invasiveness in vitro is modulated by EGF receptor signaling. Clinical and Experimental Metastasis 13, 407-419. 

24. C Reddy, A Wells, DA Lauffenburger (1996). Receptor-mediated effects on ligand availability influence relative mitogenic potencies of epidermal growth factor and transforming growth factor a. Journal of Cellular Physiology 166, 512-522. 

25. EA Lowenthal, A Wells, PD Emanuel, R Player, JT Prchal (1996). Sickle cell acute chest syndrome associated with parvovirus B19 infection. American Journal of Hematology 51, 207-213. 

26. M David, L Wong, R Flavell, SA Thompson, A Wells, AC Larner, GR Johnson (1996). STAT activation by EGF and amphiregulin: requirement for the EGF receptor kinase, but not for tyrosine phosphorylation sites or JAK1. Journal of Biological Chemistry 271, 9185-9188. 

27. P Chen, H Xie, A Wells (1996). Mitogenic signaling from the EGF receptor is attenuated by a phospholipase C- g/protein kinase C feedback mechanism. Molecular Biology of the Cell 7, 871-881. 

28. M Zhang, RK Singh, M-H Wang, A Wells, GP Siegal (1996). Epidermal growth factor modulates cell attachment to hyaluronic acid by the cell surface glycoprotein CD44. Clinical and Experimental Metastasis 14, 268-276. 

29. P Chen, J Murphy-Ullrich, A Wells (1996). A role for gelsolin in actuating EGF receptor-mediated cell motility. Journal of Cell Biology 134, 689-698. 

30. T Turner, P Chen, LJ Goodly, A Wells (1996). EGF receptor signaling enhances in vivo invasiveness of DU-145 human prostate carcinoma cells. Clinical and Experimental Metastasis 14, 409-418. 

31. M Van Epps-Fung, K Gupta, J Williford, RW Hardy, A Wells (1996). Epidermal growth factor induces glucose storage in transgenic 3T3-L1 adipocytes overexpressing epidermal growth factor receptors. Diabetes 45, 1619- 1625. 

32. CC Reddy, SK Niyogi, A Wells, HS Wiley, DA Lauffenburger (1996). Re-engineering epidermal growth factor for enhanced potency. Nature Biotechnology 14, 1696-1699. 

33. M Zhang, M-H Wang, RK Singh, A Wells, GP Siegal (1997). Epidermal growth factor induces CD44 expression through a novel regulatory element in mouse fibroblasts. Journal of Biological Chemistry 272, 14139-14146. 

34. M Van Epps-Fung, J Williford, A Wells, RW Hardy (1997). Fatty acid-induced insulin resistance in adipocytes. Endocrinology 138, 4338-4345. 

35. M Van Epps-Fung, K Gupta, R Hardy, A Wells (1997). A role for phospholipase C activity in GLUT4-mediated glucose transport. Endocrinology 138, 5170-5175. 

36. WB Parker, SA King, PW Allan, LL Bennett, JA Secrist, JA Montgomery, KS Gilbert, WR Waud, A Wells, GY Gillespie, EJ Sorscher (1997). In vivo gene therapyof cancer using E. coli purine nucleoside phosphorylase. Human Gene Therapy 8, 1637-1644. 

37. T Turner, M Van Epps-Fung, J Kassis, A Wells (1997). Molecular inhibition of PLCg signaling abrogates DU-145 prostate tumor cell invasion. Clinical Cancer Research 3, 2275-2282. 

38. T Turner, W Roberts, G R Pettit, A Wells, A Kraft (1998). Treatment of human prostate cancer with Dolastatin 10, a peptide isolated from a marine shell-less mollusk. Prostate 34, 175-181. 

39. H Xie, MA Pallero, K Gupta, MF Ware, P Chang, W Witke, DJ Kwiatkowski, DA Lauffenburger, J Murphy-Ullrich, A Wells (1998). EGF receptor regulation of cell-substratum interactions: EGF-induced disassembly of focal adhesions does not require the motility-associated PLCg signaling pathway. Journal of Cell Science 111, 616-625. 

40. CC Reddy, A Wells, DA Lauffenburger (1998).  Comparative mitogenic potencies of EGF and TGFa depend on receptor limitation versus ligand-limitation.  Medical  and Biological Engineering and Computation 36, 499-507.

41. MF Ware, A Wells, DA Lauffenburger (1998).  Epidermal growth factor increases fibroblast migration speed but decreases directional persistence in a substratum-dependent manner.  Journal of Cell Science 111, 2423-2432.

42. H Qin, JD Moellinger, A Wells, LJ Windsor, Y Sun, EN Benveniste (1998). Transcriptional suppression of matrix metalloproteinase-2 gene expression in human astroglioma cells by TNF-a and IFN-g.  Journal of Immunology 161, 6664-6673.

43.  JC Hancock, A Wells, K Tilashalski, MG Conner, CM Listinsky (1999). Composite B cell and T cell lymphoma arising 24 years after nodular lymphocyte predominant hodgkin’s disease.  Annals of Diagnostic Pathology 3, 23-34.

44.  S Khoshyomn, PL Penar, J Rossi, A Bhushan, A Wells, TR Tritton, DL Abamson (1999).  Inhibition of PLC gamma-1 activation blocks glioma cell motility and invasion of fetal rat brain aggregates. Neurosurgery 44, 568-577.

45.  JM Haugh, A Wells, HS Wiley, DA Lauffenburger (1999).  Effect of epidermal growth factor receptor internalization on regulation of the phospholipase C-g signaling pathway. Journal of Biological Chemistry 274, 8958-8965.

46. G Maheshwari, A Wells, LG Griffith, DA Lauffenburger (1999).  Crosstalk between EGF and fibronectin receptors affects fibroblast migration and underlying biophysical processes.  Biophysical Journal 76, 2814-2823.

47. L Wong, TB Debs, A Wells, SA Thompson, GR Johnson (1999).  A differential requirement for the COOH-terminal region of the EGF receptor in Amphiregulin and EGF mitogenic signaling. Journal of Biological Chemistry 274, 8900-8909.

48. H Shiraha, A Glading, K Gupta, A Wells (1999).  Chemokine transmodulation of EGF Receptor signaling:  IP-10 inhibits motility by decreasing EGF-induced calpain activity.  Journal of Cell Biology 146, 243-253.

49. KB Waites, KR Smith, MA Crum, RD Hockett, A Wells, EW Hook (1999). Detection of Chlamydia trachomatis endocervical infections by the ligase chain reaction versus the ACCESS Chlamydia antigen assay. Journal of Clinical Microbiology 37, 3072-3073.

50. JA Secrist, WB Parker, PW Allan, LL Bennett, WR Waud, JW Truss, AT Fowler, JA Montgomery, SE Ealick, AH Wells, GY Gillespie, VKGadi, EJ Sorscher (1999).  Gene therapy of cancer: activation of nucleoside prodrugs with E. coli purine nucleoside phosphorylase. Nucleosides and Nucleotides 18, 745-757.

51. J Kassis, J Moellinger, H Lo, N Greenberg, H Kim, A Wells (1999).  A role for PLCg-mediated signaling in tumor cell invasion.  Clinical Cancer Research 5, 2251-2260.

52. JM Haugh, AC Huang, HS Wiley, A Wells, DA Lauffenburger (1999). Participation of internalized epidermal growth factors receptors in the activation of p21ras.  Journal of Biological Chemistry 274, 34350-34360.

53. A Glading, P Chang, DA Lauffenburger, A Wells (2000).  EGF receptor activation of calpain is required for fibroblast motility and occurs via an ERK/MAP kinase signaling pathway. Journal of Biological Chemistry 275, 2390-2398.

54. U Marti, A Wells (2000). The nuclear accumulation of a variant epidermal growth factor receptor (EGFR) lacking the transmembrane domain requires co-expression of a full length EGFR. Molecular Cell Biology Research Communications 3, 8-14.

55. G Maheshwari, G Brown, DA Lauffenburger, A Wells, LG Griffith (2000). Cell adhesion and motility depend on nanoscale RGD clustering. Journal of Cell Science 113, 1677-1686.

56. H Shiraha, K Gupta, KA Drabik, A Wells (2000).  Preferential loss of epiderml growth factor receptor results in reduced responsiveness in aging dermal fibroblasts.  Journal of Biological Chemistry 275, 19343-19351.

57. JM Haugh, A Wells, DA Lauffenburger (2000).  Mathematical modeling of epidermal growth factor receptor signaling through the Phospholipase C pathway:  mechanistics insights and predictions for molecular interventions.  Biotechnology and Bioengineering 70, 225-238.

58. MA Barbieri, R Roberts, A Gumusboga, H Highfield, C Alvarez-Dominguez, A Wells, PD Stahl (2000).  Signal transduction and membrane trafficking:  activation of MAP kinase and endocytosis by the EGF receptor requires Rab 5a.  Journal of Cell Biology 151, 539-550.

59.  RJ Botelho, M Teruel, R Dierckman, R Anderson,  A Wells, JD York, T Meyer, S Grinstein (2000).  Localized changes in phosphatidylinositol-4,5-bisphosphate metabolism during Fcg receptor-mediated phagocytosis. Journal of Cell Biology 151, 1353-1367.

60. TB Deb, L Su, L Wong, E Bonvini, A Wells, M David, GR Johnson (2001). EGF receptor kinase-independent signaling by EGF.  Journal of Biological Chemistry 276, 1554-15560.

61. EJ Manos, M Kim, J Kassis, B Chang, A Wells, DA Jones (2001). Dolichol-phosphate-mannose-3 (DPM3)/prostin-1 is a novel phospholipase C-gamma regulated gene negatively associated with prostate tumor invasion. Oncogene 20, 2781-2790.

62. A Glading, F Uberall, SM Keyse, DA Lauffenburger, A Wells (2001).  Membrane proximal ERK signaling is required for M-calpain activation downstream of EGF receptor signaling. Journal of Biological Chemistry 276, 23341-23348.

63. CS Swindel, KT Tran, TD Johnson, P Banerjee, AM Mayes, LG Griffith, A Wells (2001). Direct activation of the epidermal growth factor receptor by EGF-like repeats of human tenascin-C. Journal of Cell Biology, in press.

64. MA Barbieri, CM Heath, EM Peters, A Wells, NJ Davis, PD Stahl (2001). Phosphatidylinositol-4-phosphate 5-kinase-1? is essential for epidermal growth factor receptor-mediated endocytosis. Journal of Biological Chemistry 276, 47212-47216.

65. H Shiraha, A Glading, J Chou, Z Jia, A Wells (2002). Activation of M-calpain (calpain II) by epidermal growth factor is inhibited by PKA phosphorylation of M-calpain. Molecular and Cellular Biology 22, 2716-2727.

66. A Wells, JCS. Souto, J Solava, J Kassis, KJ Bailey, T Turner (2002). LHRH agonist limits DU-145 prostate cancer growth by attenuating EGF receptor signaling. Clinical Cancer Research 8, 1251-1257.

67. J Kassis, R Radinsky, A Wells (2002). Motility is rate-limiting for invasion of bladder carcinoma cell lines. International Journal of Biochemistry and Cell Biology 34, 762-775.

68. J Chou, D Beer-Stolz, NA Burke, SC Watkins, A Wells (2002). Distribution of gelsolin and phosphoinositol 4,5-bisphosphate in lamellipodia during EGF-induced motility. International Journal of Biochemistry and Cell Biology 34, 776-790.

69. FD Allen, CF Asnes, P Chang, EL Elson, DA Lauffenburger, A Wells (2002). EGF-induced matrix contraction is modulated by calpain. Wound Repair and Regeneration 10, 67-76.

70. J Kassis, A Maeda, N Teramoto, K Takada, C Wu, G Klein, A Wells (2002). EBV-expressing AGS gastric carcinoma cell sublines present increased motility and invasiveness. International Journal of Cancer 99, 644-651.

Invited publications: 

1. A Wells (1982). Characterization of the Epstein-Barr virus receptor. Thesis (Karolinska Inst, Stockholm, Sweden). 

2. A Wells (1989). The epidermal growth factor receptor and its ligands. in Oncogenes (S Benz and E Lui, eds.) Kluwer Academic Publishers,143-168. 

3. DA Lauffenburger, L Chu, A French, F Oehrtman, C Reddy, B Will, A Wells, HS Wiley (1996). Engineering dynamics of growth factors and other therapeutic ligands. Biotechnology and Bioengineering 52, 61-80. 

4. RW Hardy, NSMD Wickramasinghe, A Wells (1997). Fatty acids and breast cancer cell proliferation. Advances in Experimental Medicine and Biology 422, 57-69.

5. A Wells, K Gupta, P Chang, S Swindle, A Glading, H Shiraha (1998).  Epidermal growth factor receptor-mediated motility in fibroblasts.  Microscopy Research and Technique 43, 395-411.

6. H Kim, T Turner, J Kassis, A Wells (1999).  EGF receptor signaling in prostate development.  Histology and Histopathology, in press.

7. A Wells (1999).  Molecule in Focus:  EGF receptor.  International Journal of Biochemistry and Cell Biology 31,637-643.

8. A Wells, MF Ware, FD Allen, DA Lauffenburger (1999).  Shapping up for shipping out:  PLCg signaling of morphology changes in EGF-stimulated fibroblast migration.  Cell Motility and the Cytoskeleton 44, 227-233.

9. A Wells (2000). Tumor invasion: role of growth factor-induced cell motility.  Advances in Cancer Research 78, 31-101.

10. J Kassis, DA Lauffenburger, T Turner, A Wells (2001).  Tumor invasion as dysregulated cell motility.  Seminars in Cancer Biology 11, 105-119.

11. A Wells (2000). The epidermal growth factor receptor ? a new target in cancer therapy. Signal 1, 4-10.

12.  A Wells (2001).  The EGF receptor signaling system: a model for growth factor receptor signaling.  Hormone Signaling, in press.

13. DA Lauffenburger, A Wells (2001).  Getting a grip: new insights for cell adhesion and traction. Nature Cell Biology 3, E110-112.

15. A Glading, DA Lauffenburger, A Wells (2002). Cutting to the chase: calpain proteases in cell motility. Trends in Cell Biology 12, 46-54.

16. A Wells, J Kassis, J Solava, T Turner, DA Lauffenburger (2002). Growth factor-induced cell motility in tumor invasion. Acta Oncologica 41, 124-130.

17. A Wells, U Marti (2002). Signalling shortcuts: Cell surface receptors in the nucleus? Nature Reviews Molecular Cell Biology 3, 967-702.

18. A. Wells, A Huttenlocher (2003). Calpain. in Handbook of Cellular Signaling (Eds: RA Bradshaw, E Dennis, Academic Press). in press.

19. A Wells, JR Grandis (2003). PLC?-1 in tumor progression. Clinical & Experimental Metastasis, in press.