John P Lynch

Summary

Affiliation: University of Pennsylvania
Country: USA

Publications

  1. pmc Ectopic Cdx2 expression in murine esophagus models an intermediate stage in the emergence of Barrett's esophagus
    Jianping Kong
    Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
    PLoS ONE 6:e18280. 2011
  2. ncbi request reprint The genetic pathogenesis of colorectal cancer
    John P Lynch
    Division of Gastroenterology, Department of Medicine, University of Pennsylvania, 415 Curie, Boulevard, Philadelphia, PA 19104, USA
    Hematol Oncol Clin North Am 16:775-810. 2002
  3. ncbi request reprint Cdx1 inhibits the proliferation of human colon cancer cells by reducing cyclin D1 gene expression
    John Lynch
    Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Oncogene 22:6395-407. 2003
  4. pmc Cdx2 levels modulate intestinal epithelium maturity and Paneth cell development
    Mary Ann S Crissey
    Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Gastroenterology 140:517-528.e8. 2011
  5. pmc The homeodomain transcription factor Cdx1 does not behave as an oncogene in normal mouse intestine
    Mary Ann S Crissey
    Division of Gastroenterology, Department of Medicine, University of Pennsylvania, 600 Clinical Research Building, 415 Curie Blvd, Philadelphia, PA 19104 USA
    Neoplasia 10:8-19. 2008
  6. pmc Intestine-specific transcription factor Cdx2 induces E-cadherin function by enhancing the trafficking of E-cadherin to the cell membrane
    Shinsuke Funakoshi
    Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Am J Physiol Gastrointest Liver Physiol 299:G1054-67. 2010
  7. ncbi request reprint The homeodomain transcription factors Cdx1 and Cdx2 induce E-cadherin adhesion activity by reducing beta- and p120-catenin tyrosine phosphorylation
    Toshihiko Ezaki
    Division of Gastroenterology 650 CRB, Department of Medicine, University of Pennsylvania, 415 Curie Blvd, Philadelphia, PA 19104, USA
    Am J Physiol Gastrointest Liver Physiol 293:G54-65. 2007
  8. ncbi request reprint Cdx1 inhibits human colon cancer cell proliferation by reducing beta-catenin/T-cell factor transcriptional activity
    Rong Jun Guo
    Division of Gastroenterology, The Department of Medicine, University of Pennsylvania, 415 Curie Boulevard, Philadelphia, PA 19104, USA
    J Biol Chem 279:36865-75. 2004
  9. pmc Induction of intestinalization in human esophageal keratinocytes is a multistep process
    Jianping Kong
    Department of Medicine, Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Carcinogenesis 30:122-30. 2009
  10. pmc Cox2 and β-catenin/T-cell factor signaling intestinalize human esophageal keratinocytes when cultured under organotypic conditions
    Jianping Kong
    Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    Neoplasia 13:792-805. 2011

Collaborators

Detail Information

Publications23

  1. pmc Ectopic Cdx2 expression in murine esophagus models an intermediate stage in the emergence of Barrett's esophagus
    Jianping Kong
    Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
    PLoS ONE 6:e18280. 2011
    ..These altered cells represent a transitional cell type between normal squamous and columnar BE cells. The K14-Cdx2 mice represent a useful model to study progression from squamous epithelium to BE...
  2. ncbi request reprint The genetic pathogenesis of colorectal cancer
    John P Lynch
    Division of Gastroenterology, Department of Medicine, University of Pennsylvania, 415 Curie, Boulevard, Philadelphia, PA 19104, USA
    Hematol Oncol Clin North Am 16:775-810. 2002
    ..Increasingly rapid research developments and technologic advances will transform the way we prevent, diagnose, and treat this common and deadly form of cancer...
  3. ncbi request reprint Cdx1 inhibits the proliferation of human colon cancer cells by reducing cyclin D1 gene expression
    John Lynch
    Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Oncogene 22:6395-407. 2003
    ..We conclude that Cdx1 reduces the proliferation of human colon cancer cells by reducing cyclin D1 gene transcription...
  4. pmc Cdx2 levels modulate intestinal epithelium maturity and Paneth cell development
    Mary Ann S Crissey
    Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Gastroenterology 140:517-528.e8. 2011
    ..We generated transgenic mice that overexpress Cdx2 in the small intestinal and colonic epithelium to investigate the role of Cdx2 in differentiation and function of the intestinal epithelium...
  5. pmc The homeodomain transcription factor Cdx1 does not behave as an oncogene in normal mouse intestine
    Mary Ann S Crissey
    Division of Gastroenterology, Department of Medicine, University of Pennsylvania, 600 Clinical Research Building, 415 Curie Blvd, Philadelphia, PA 19104 USA
    Neoplasia 10:8-19. 2008
    ..Our results therefore suggest that Cdx1 is not an oncogene in normal intestinal epithelium...
  6. pmc Intestine-specific transcription factor Cdx2 induces E-cadherin function by enhancing the trafficking of E-cadherin to the cell membrane
    Shinsuke Funakoshi
    Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Am J Physiol Gastrointest Liver Physiol 299:G1054-67. 2010
    ..This novel mechanism advances Cdx2's prodifferentiation and antitumor properties and suggests that Cdx2 may broadly regulate RTK activity in normal intestinal epithelium by modulating membrane trafficking of proteins...
  7. ncbi request reprint The homeodomain transcription factors Cdx1 and Cdx2 induce E-cadherin adhesion activity by reducing beta- and p120-catenin tyrosine phosphorylation
    Toshihiko Ezaki
    Division of Gastroenterology 650 CRB, Department of Medicine, University of Pennsylvania, 415 Curie Blvd, Philadelphia, PA 19104, USA
    Am J Physiol Gastrointest Liver Physiol 293:G54-65. 2007
    ..Ascertaining the mechanism for this novel Cdx effect may improve our understanding of the regulation of cell-cell adhesion in the colonic epithelium...
  8. ncbi request reprint Cdx1 inhibits human colon cancer cell proliferation by reducing beta-catenin/T-cell factor transcriptional activity
    Rong Jun Guo
    Division of Gastroenterology, The Department of Medicine, University of Pennsylvania, 415 Curie Boulevard, Philadelphia, PA 19104, USA
    J Biol Chem 279:36865-75. 2004
    ..We conclude that Cdx1 and Cdx2 inhibit colon cancer cell proliferation by blocking beta-catenin/TCF transcriptional activity...
  9. pmc Induction of intestinalization in human esophageal keratinocytes is a multistep process
    Jianping Kong
    Department of Medicine, Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Carcinogenesis 30:122-30. 2009
    ..We conclude that ectopic proliferation signals, alterations in epigenetic gene regulation and the inhibition of tumor suppressor mechanisms are required for Cdx2-mediated intestinalization of human esophageal keratinocytes in BE...
  10. pmc Cox2 and β-catenin/T-cell factor signaling intestinalize human esophageal keratinocytes when cultured under organotypic conditions
    Jianping Kong
    Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    Neoplasia 13:792-805. 2011
    ..We conclude that in vitro modeling of BE pathogenesis can be improved by enhancing Wnt signaling and Cox2 activity and using three-dimensional organotypic culture conditions...
  11. doi request reprint Repression of the desmocollin 2 gene expression in human colon cancer cells is relieved by the homeodomain transcription factors Cdx1 and Cdx2
    Shinsuke Funakoshi
    Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Mol Cancer Res 6:1478-90. 2008
    ..The regulation of desmosomal junctions by Cdx contributes to normal intestinal epithelial columnar morphology and likely antagonizes the epithelial-to-mesenchymal transition necessary for the metastasis of colon cancer cells in humans...
  12. pmc Cdx1 and c-Myc foster the initiation of transdifferentiation of the normal esophageal squamous epithelium toward Barrett's esophagus
    Douglas B Stairs
    Division of Gastroenterology, Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    PLoS ONE 3:e3534. 2008
    ..Despite this well-defined epidemiologic association between acid reflux and Barrett's esophagus, the genetic changes that induce this transdifferentiation process in esophageal keratinocytes have remained undefined...
  13. pmc Math1/Atoh1 contributes to intestinalization of esophageal keratinocytes by inducing the expression of Muc2 and Keratin-20
    Jianping Kong
    Department of Medicine, Division of Gastroenterology, University of Pennsylvania, 650 CRB 415 Curie Blvd, Philadelphia, PA 19104, USA
    Dig Dis Sci 57:845-57. 2012
    ..Barrett's esophagus is an important risk factor for adenocarcinoma development. In-vitro models for Barrett's esophagus have not, to date, focused on the induction of goblet cells in Barrett's epithelium...
  14. pmc The intestine-specific transcription factor Cdx2 inhibits beta-catenin/TCF transcriptional activity by disrupting the beta-catenin-TCF protein complex
    Rong Jun Guo
    Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Carcinogenesis 31:159-66. 2010
    ....
  15. ncbi request reprint Intestinal metaplasia with a high salt diet induces epithelial proliferation and alters cell composition in the gastric mucosa of mice
    Fang Xiao
    Gastroenterology Division, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Cancer Biol Ther 4:669-75. 2005
    ..Alteration in the composition of the gastric epithelium may play a role in influencing the microenvironment to engender susceptibility to carcinogens...
  16. pmc H. pylori infection is associated with DNA damage of Lgr5-positive epithelial stem cells in the stomach of patients with gastric cancer
    Takeshi Uehara
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 3400 Spruce Street, Founders 6, Philadelphia, PA 19104, USA
    Dig Dis Sci 58:140-9. 2013
    ..H. pylori (Hp) infection is a major risk factor in gastric carcinogenesis leading to epithelial mutagenesis, and may affect gastric epithelial stem cells...
  17. doi request reprint Modelling Barrett's oesophagus
    Jianping Kong
    Division of Gastroenterology, Department of Medicine, University of Pennsylvania, 415 Curie Boulevard, Philadelphia, PA 19104, USA
    Biochem Soc Trans 38:321-6. 2010
    ..Moreover, our findings suggest that it may be possible to induce Barrett's oesophagus epithelial cells from oesophageal keratinocytes by altering the expression of certain critical genes...
  18. pmc Acid and bile salt-induced CDX2 expression differs in esophageal squamous cells from patients with and without Barrett's esophagus
    Xiaofang Huo
    Department of Medicine, VA North Texas Health Care System and the University of Texas Southwestern Medical School, Dallas, Texas, USA
    Gastroenterology 139:194-203.e1. 2010
    ..We hypothesized that differences among individuals in molecular pathways activated when esophageal squamous epithelium is exposed to reflux underlie the development of Barrett's metaplasia...
  19. doi request reprint Cdx genes, inflammation, and the pathogenesis of intestinal metaplasia
    Douglas B Stairs
    Department of Medicine, Division of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Prog Mol Biol Transl Sci 96:231-70. 2010
    ..We review the observations regarding the role of chronic inflammation and the Cdx transcription factors in the pathogenesis of gastric IM and BE...
  20. ncbi request reprint Cdx1 or Cdx2 expression activates E-cadherin-mediated cell-cell adhesion and compaction in human COLO 205 cells
    Matthew S Keller
    Division of Gastroenterology 660 CRB, University of Pennsylvania, 415 Curie Blvd, Philadelphia, PA 19104, USA
    Am J Physiol Gastrointest Liver Physiol 287:G104-14. 2004
    ..Ascertaining the mechanism for this novel Cdx effect may yield insight into the development of mature colonic epithelium...
  21. ncbi request reprint The role of Cdx proteins in intestinal development and cancer
    Rong Jun Guo
    Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Cancer Biol Ther 3:593-601. 2004
    ..This review will explore our current understanding of the roles of the caudal homologues Cdx1 and Cdx2 in intestinal development and carcinogenesis...
  22. pmc Autophagy inhibitor Lys05 has single-agent antitumor activity and reproduces the phenotype of a genetic autophagy deficiency
    Quentin McAfee
    Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 109:8253-8. 2012
    ..Unlike HCQ, significant single-agent antitumor activity is observed without toxicity in mice treated with lower doses of Lys05, establishing the therapeutic potential of this compound in cancer...
  23. ncbi request reprint To differentiate or proliferate? The interaction between PI3K/PTEN and Cdx2
    John P Lynch
    Gastroenterology 123:1395-7. 2002

Research Grants12

  1. REGULATION OF INTESTINAL EPITHELIAL CELL PROLIFERATION
    John Lynch; Fiscal Year: 2004
    ..It will also enhance our understanding of the events leading to dysregulation of proliferation and human colon cancers. ..
  2. Cdx2 modulates beta-catenin activity in intestinal cells
    John Lynch; Fiscal Year: 2007
    ..As a result, potential novel targeted therapeutics mayalso emerge. ..
  3. Cdx2 modulates beta-catenin activity in intestinal cells
    John Lynch; Fiscal Year: 2006
    ..abstract_text> ..
  4. Cdx2 modulates beta-catenin activity in intestinal cells
    John P Lynch; Fiscal Year: 2010
    ..As a result, potential novel targeted therapeutics mayalso emerge. ..
  5. Cdx2 modulates beta-catenin activity in intestinal cells
    John Lynch; Fiscal Year: 2009
    ..As a result, potential novel targeted therapeutics mayalso emerge. ..