J. Thomas Parsons

Education

  • BA, Depauw University, Greencastle, IN
  • Postdoc, St. Louis University, St Louis, MO
  • PhD, Duke University, Durham, NC
  • Postdoc, Universitat Zurich, Zurich, Switzerland

Primary Appointment

  • Professor, Unaffiliated

Contact

Research Interest(s)

Adhesion Signaling in Normal, Cardiovascular and Cancer Cells

Research Description

Growth Factor and Adhesion Signaling. For the past 25 years my laboratory has been interested in how the activation of protein tyrosine kinases contributes to cancer progression and metastasis. In 1991 we identified Focal Adhesion Kinase (FAK) as an integrin regulated tyrosine protein kinase and in the ensuing years identified and characterized the signaling pathways regulated by adhesion to the extracellular matrix. Our studies have helped to define the role of FAK in tumor initiation, progression and metastasis and have laid ground work for efforts to develop small molecule inhibitors to FAK. We have helped to characterize one such inhibitor that has gone on to phase I trials in cancer patients. In the past 10 years my laboratory has focused on how receptor and non-receptor tyrosine kinase signaling contributes to tumor growth and metabolism and response to therapies, with particular interest in the tumor microenvironment. This interest has manifested itself in a highly productive and interactive collaboration with Todd Bauer, Associate Professor of Surgery and led to the establishment of patient-derived xenografts of pancreatic cancer as a model to develop effective combinatorial therapies for pancreatic adenocarcinomas. We have further developed mouse models that recapitulate the steps in the metastatic outgrowth of pancreas cancers in the liver. We are using these models to identify novel therapies for patients with recurrent metastatic disease.

Selected Publications

  • Reynolds A, Kanner S, Bouton A, Schaller M, Weed S, Flynn D, Parsons J. SRChing for the substrates of Src. Oncogene. 2013. PMID: 24121272
  • Walters D, Lindberg J, Adair S, Newhook T, Cowan C, Stokes J, Borgman C, Stelow E, Lowrey B, Chopivsky M, Gilmer T, Parsons J, Bauer T. Inhibition of the growth of patient-derived pancreatic cancer xenografts with the MEK inhibitor trametinib is augmented by combined treatment with the epidermal growth factor receptor/HER2 inhibitor lapatinib. Neoplasia (New York, N.Y.). 2013;15(2): 143-55. PMID: 23441129
  • Walters D, Stokes J, Adair S, Stelow E, Borgman C, Lowrey B, Xin W, Blais E, Lee J, Papin J, Parsons J, Bauer T. Clinical, molecular and genetic validation of a murine orthotopic xenograft model of pancreatic adenocarcinoma using fresh human specimens. PloS one. 2013;8(10): e77065. PMID: 24204737
  • Grigera P, Ma L, Borgman C, Pinto A, Sherman N, Parsons J, Fox J. Mass spectrometric analysis identifies a cortactin-RCC2/TD60 interaction in mitotic cells. Journal of proteomics. 2012;75(7): 2153-9. PMID: 22282019 | PMCID: PMC3312979
  • Guerrero M, Parsons J, Bouton A. Cas and NEDD9 Contribute to Tumor Progression through Dynamic Regulation of the Cytoskeleton. Genes & cancer. 2012;3(5): 371-81. PMID: 23226575
  • Tilghman R, Blais E, Cowan C, Sherman N, Grigera P, Jeffery E, Fox J, Blackman B, Tschumperlin D, Papin J, Parsons J. Matrix rigidity regulates cancer cell growth by modulating cellular metabolism and protein synthesis. PloS one. 2012;7(5): e37231. PMID: 22623999 | PMCID: PMC3356407
  • Stokes J, Adair S, Slack-Davis J, Walters D, Tilghman R, Hershey E, Lowrey B, Thomas K, Bouton A, Hwang R, Stelow E, Parsons J, Bauer T. Inhibition of focal adhesion kinase by PF-562,271 inhibits the growth and metastasis of pancreatic cancer concomitant with altering the tumor microenvironment. Molecular cancer therapeutics. 2011;10(11): 2135-45. PMID: 21903606 | PMCID: PMC3213273
  • Parsons J, Horwitz A, Schwartz M. Cell adhesion: integrating cytoskeletal dynamics and cellular tension. Nature reviews. Molecular cell biology. 2010;11(9): 633-43. PMID: 20729930 | PMCID: PMC2992881
  • Tilghman R, Cowan C, Mih J, Koryakina Y, Gioeli D, Slack-Davis J, Blackman B, Tschumperlin D, Parsons J. Matrix rigidity regulates cancer cell growth and cellular phenotype. PloS one. 2010;5(9): e12905. PMID: 20886123 | PMCID: PMC2944843
  • Iwanicki M, Vomastek T, Tilghman R, Martin K, Banerjee J, Wedegaertner P, Parsons J. FAK, PDZ-RhoGEF and ROCKII cooperate to regulate adhesion movement and trailing-edge retraction in fibroblasts. J Cell Sci. 2008;121(6): 895-905.
  • Iwanicki M, Vomastek T, Tilghman R, Martin K, Banerjee J, Wedegaertner P, Parsons J. FAK, PDZ-RhoGEF and ROCKII cooperate to regulate adhesion movement and trailing-edge retraction in fibroblasts. Journal of cell science. 2008;121 895-905. PMID: 18303050
  • Parsons J, Slack-Davis J, Tilghman R, Roberts W. Focal adhesion kinase: targeting adhesion signaling pathways for therapeutic intervention. Clin Cancer Res. 2008;14(3): 627-32.
  • Parsons J, Slack-Davis J, Tilghman R, Roberts W. Focal adhesion kinase: targeting adhesion signaling pathways for therapeutic intervention. Clinical cancer research : an official journal of the American Association for Cancer Research. 2008;14(3): 627-32. PMID: 18245520
  • Sayers R, Sundberg-Smith L, Rojas M, Hayasaka H, Parsons J, Mack C, Taylor J. FRNK expression promotes smooth muscle cell maturation during vascular development and after vascular injury. Arterioscler Thromb Vasc Biol. 2008;28(12): 2115-22. PMCID: PMC2785047
  • Tilghman R, Parsons J. Focal adhesion kinase as a regulator of cell tension in the progression of cancer. Semin Cancer Biol. 2008;18(1): 45-52. PMCID: PMC2267763
  • Vomastek T, Iwanicki M, Burack W, Tiwari D, Kumar D, Parsons J, Weber M, Nandicoori V. Extracellular signal-regulated kinase 2 (ERK2) phosphorylation sites and docking domain on the nuclear pore complex protein Tpr cooperatively regulate ERK2-Tpr interaction. Mol Cell Biol. 2008;28(22): 6954-66. PMCID: PMC2573295
  • Slack-Davis J, Martin K, Tilghman R, Iwanicki M, Ung E, Autry C, Luzzio M, Cooper B, Kath J, Roberts W, Parsons J. Cellular characterization of a novel focal adhesion kinase inhibitor. The Journal of biological chemistry. 2007;282(20): 14845-52. PMID: 17395594
  • Webb D, Donais K, Whitmore L, Thomas S, Turner C, Parsons J, Horwitz A. FAK-Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly. Nature cell biology. 2004;6(2): 154-61. PMID: 14743221
  • Ridley A, Schwartz M, Burridge K, Firtel R, Ginsberg M, Borisy G, Parsons J, Horwitz A. Cell migration: integrating signals from front to back. Science (New York, N.Y.). 2003;302(5651): 1704-9. PMID: 14657486
  • Bernaciak T, Zareno J, Parsons J, Silva C. A novel role for signal transducer and activator of transcription 5b (STAT5b) in beta1-integrin-mediated human breast cancer cell migration. Breast Cancer Res. 11(4): R52. PMCID: PMC2750113
  • Hayasaka H, Martin K, Hershey E, Parsons J. Disruption of FRNK expression by gene targeting of the intronic promoter within the focal adhesion kinase gene. J Cell Biochem. 102(4): 947-54.
  • Martin K, Jeffery E, Grigera P, Shabanowitz J, Hunt D, Parsons J. Cortactin phosphorylation sites mapped by mass spectrometry. J Cell Sci. 119 2851-3.
  • Mayhew M, Jeffery E, Sherman N, Nelson K, Polefrone J, Pratt S, Shabanowitz J, Parsons J, Fox J, Hunt D, Horwitz A. Identification of phosphorylation sites in betaPIX and PAK1. J Cell Sci. 120 3911-8.
  • Owen K, Pixley F, Thomas K, Vicente-Manzanares M, Ray B, Horwitz A, Parsons J, Beggs H, Stanley E, Bouton A. Regulation of lamellipodial persistence, adhesion turnover, and motility in macrophages by focal adhesion kinase. J Cell Biol. 179(6): 1275-87. PMCID: PMC2140030
  • Parsons J, Horwitz A, Schwartz M. Cell adhesion: integrating cytoskeletal dynamics and cellular tension. Nat Rev Mol Cell Biol. 11(9): 633-43.
  • Petzold T, Orr A, Hahn C, Jhaveri K, Parsons J, Schwartz M. Focal adhesion kinase modulates activation of NF-kappaB by flow in endothelial cells. Am J Physiol Cell Physiol. 297(4): C814-22. PMCID: PMC2770750
  • Slack-Davis J, Hershey E, Theodorescu D, Frierson H, Parsons J. Differential requirement for focal adhesion kinase signaling in cancer progression in the transgenic adenocarcinoma of mouse prostate model. Mol Cancer Ther. 8(8): 2470-7. PMCID: PMC2728172
  • Vomastek T, Iwanicki M, Schaeffer H, Tarcsafalvi A, Parsons J, Weber M. RACK1 targets the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway to link integrin engagement with focal adhesion disassembly and cell motility. Mol Cell Biol. 27(23): 8296-305. PMCID: PMC2169169
  • Zhang X, Yuan Z, Zhang Y, Yong S, Salas-Burgos A, Koomen J, Olashaw N, Parsons J, Yang X, Dent S, Yao T, Lane W, Seto E. HDAC6 modulates cell motility by altering the acetylation level of cortactin. Mol Cell. 27(2): 197-213. PMCID: PMC2684874