Steven D Leach

Summary

Affiliation: Johns Hopkins University
Country: USA

Publications

  1. pmc Wnt/beta-catenin signaling is required for development of the exocrine pancreas
    James M Wells
    Department of Developmental Biology, Cincinnati Children s Hospital Research 45267, Cincinnati, OH 45267, USA
    BMC Dev Biol 7:4. 2007
  2. ncbi request reprint Mouse models of pancreatic cancer: the fur is finally flying!
    Steven D Leach
    The Sidney Kimmel Cancer Center at Johns Hopkins, 600 North Wolfe Street Osler 603, Baltimore, MD 21287, USA
    Cancer Cell 5:7-11. 2004
  3. pmc Oncogenic KRAS induces progenitor cell expansion and malignant transformation in zebrafish exocrine pancreas
    Seung Woo Park
    Department of Surgery, The Sol Goldman Center for Pancreatic Cancer Research, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Gastroenterology 134:2080-90. 2008
  4. pmc Hedgehog signaling is required for effective regeneration of exocrine pancreas
    Volker Fendrich
    Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Gastroenterology 135:621-31. 2008
  5. pmc Ribosomal biogenesis genes play an essential and p53-independent role in zebrafish pancreas development
    Elayne Provost
    Department of Surgery, Johns Hopkins University, Baltimore, MD 21205, USA
    Development 139:3232-41. 2012
  6. pmc Notch-responsive cells initiate the secondary transition in larval zebrafish pancreas
    Michael J Parsons
    Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Mech Dev 126:898-912. 2009
  7. ncbi request reprint Gene expression alterations in the non-neoplastic parenchyma adjacent to infiltrating pancreatic ductal adenocarcinoma
    Noriyoshi Fukushima
    Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD 21205 2196, USA
    Mod Pathol 18:779-87. 2005
  8. doi request reprint Screening pancreatic oncogenes in zebrafish using the Gal4/UAS system
    Shu Liu
    Department of Surgery and McKusick Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Methods Cell Biol 105:367-81. 2011
  9. doi request reprint Characterization of Kras-mediated pancreatic tumorigenesis in zebrafish
    Jon M Davison
    Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Methods Enzymol 438:391-417. 2008
  10. pmc Repression of the miR-143/145 cluster by oncogenic Ras initiates a tumor-promoting feed-forward pathway
    Oliver A Kent
    Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Genes Dev 24:2754-9. 2010

Research Grants

Detail Information

Publications51

  1. pmc Wnt/beta-catenin signaling is required for development of the exocrine pancreas
    James M Wells
    Department of Developmental Biology, Cincinnati Children s Hospital Research 45267, Cincinnati, OH 45267, USA
    BMC Dev Biol 7:4. 2007
    ..A Pdx1-cre mouse line was used to delete a floxed beta-catenin allele specifically in the developing pancreas, and embryonic pancreata were studied by immunohistochemistry and microarray analysis...
  2. ncbi request reprint Mouse models of pancreatic cancer: the fur is finally flying!
    Steven D Leach
    The Sidney Kimmel Cancer Center at Johns Hopkins, 600 North Wolfe Street Osler 603, Baltimore, MD 21287, USA
    Cancer Cell 5:7-11. 2004
    ....
  3. pmc Oncogenic KRAS induces progenitor cell expansion and malignant transformation in zebrafish exocrine pancreas
    Seung Woo Park
    Department of Surgery, The Sol Goldman Center for Pancreatic Cancer Research, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Gastroenterology 134:2080-90. 2008
    ..To examine the effects of oncogene activation within the pancreatic progenitor pool, we devised a system for real-time visualization of both normal and oncogenic KRAS-expressing pancreatic progenitor cells in living zebrafish embryos...
  4. pmc Hedgehog signaling is required for effective regeneration of exocrine pancreas
    Volker Fendrich
    Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Gastroenterology 135:621-31. 2008
    ..Given the known role of Hh signaling in exocrine pancreatic cancer, these findings may provide a mechanistic link between injury-induced activation of pancreatic progenitors and subsequent pancreatic neoplasia...
  5. pmc Ribosomal biogenesis genes play an essential and p53-independent role in zebrafish pancreas development
    Elayne Provost
    Department of Surgery, Johns Hopkins University, Baltimore, MD 21205, USA
    Development 139:3232-41. 2012
    ..The pancreatic phenotypes observed in rpl3- and pes-deficient embryos were also independent of p53. Together, these data suggest novel p53-independent roles for ribosomal biogenesis genes in zebrafish pancreas development...
  6. pmc Notch-responsive cells initiate the secondary transition in larval zebrafish pancreas
    Michael J Parsons
    Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Mech Dev 126:898-912. 2009
    ..We also show that Notch-responsive cells persist in the adult pancreas and possess the classical characteristics of centroacinar cells, a cell type believed to be a multipotent progenitor cell in adult mammalian pancreas...
  7. ncbi request reprint Gene expression alterations in the non-neoplastic parenchyma adjacent to infiltrating pancreatic ductal adenocarcinoma
    Noriyoshi Fukushima
    Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD 21205 2196, USA
    Mod Pathol 18:779-87. 2005
    ....
  8. doi request reprint Screening pancreatic oncogenes in zebrafish using the Gal4/UAS system
    Shu Liu
    Department of Surgery and McKusick Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Methods Cell Biol 105:367-81. 2011
    ..We also describe techniques used to identify and characterize pancreatic tumors in adult transgenic fish...
  9. doi request reprint Characterization of Kras-mediated pancreatic tumorigenesis in zebrafish
    Jon M Davison
    Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Methods Enzymol 438:391-417. 2008
    ....
  10. pmc Repression of the miR-143/145 cluster by oncogenic Ras initiates a tumor-promoting feed-forward pathway
    Oliver A Kent
    Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Genes Dev 24:2754-9. 2010
    ..Additionally, KRAS and RREB1 are targets of miR-143/miR-145, revealing a feed-forward mechanism that potentiates Ras signaling...
  11. pmc Spontaneous induction of murine pancreatic intraepithelial neoplasia (mPanIN) by acinar cell targeting of oncogenic Kras in adult mice
    Nils Habbe
    Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 105:18913-8. 2008
    ....
  12. pmc In vivo imaging of zebrafish digestive organ function using multiple quenched fluorescent reporters
    Kotaro Hama
    Department of Embriology, Carnegie Institution, Baltimore, MD 21224, USA
    Am J Physiol Gastrointest Liver Physiol 296:G445-53. 2009
    ..Thus the multiple fluorescent reporter-based methodology facilitates the rapid analysis of digestive organ function in live zebrafish larvae...
  13. doi request reprint Sphere-forming assays for assessment of benign and malignant pancreatic stem cells
    YUE J WANG
    McKusick Nathans Institute of Genetic Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA
    Methods Mol Biol 980:281-90. 2013
    ..Here we briefly review both the capabilities of pancreatosphere and pancreatic tumorsphere assays, discuss important caveats regarding their use, and provide detailed protocols for the assay of both normal and neoplastic cells...
  14. pmc Isolation and characterization of centroacinar/terminal ductal progenitor cells in adult mouse pancreas
    Meritxell Rovira
    Department of Surgery and McKusick Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 107:75-80. 2010
    ..These findings suggest that CA/TD cells are indeed capable of progenitor function and may contribute to the maintenance of tissue homeostasis in adult mouse pancreas...
  15. doi request reprint Gal4/UAS transgenic tools and their application to zebrafish
    Marnie E Halpern
    Carnegie Institution for Science, Baltimore, Maryland, USA
    Zebrafish 5:97-110. 2008
    ..We describe some exciting new directions, in large part afforded by the Tol2 transposition system, that are generating valuable new Gal4/UAS reagents for zebrafish research...
  16. ncbi request reprint Viral 2A peptides allow expression of multiple proteins from a single ORF in transgenic zebrafish embryos
    Elayne Provost
    Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Genesis 45:625-9. 2007
    ..The successful application of this technology in zebrafish will be valuable for visually marking transgenic embryos and transgene-expressing cells, or in any situation where reliable expression of multiple transgenes is desired...
  17. pmc Transactivation from Gal4-VP16 transgenic insertions for tissue-specific cell labeling and ablation in zebrafish
    Jon M Davison
    Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Dev Biol 304:811-24. 2007
    ....
  18. ncbi request reprint Differential requirement for ptf1a in endocrine and exocrine lineages of developing zebrafish pancreas
    John W Lin
    Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA
    Dev Biol 270:474-86. 2004
    ..Together, these findings suggest the presence of distinct ptf1a-dependent and ptf1a-independent precursor populations in developing zebrafish pancreas...
  19. ncbi request reprint Expression of the caudal-type homeodomain transcription factors CDX 1/2 and outcome in carcinomas of the ampulla of Vater
    Donna E Hansel
    MBBS, Department of Surgery, The Johns Hopkins University School of Medicine, 720 Rutland Ave, Ross 771, Baltimore, MD 21205, USA
    J Clin Oncol 23:1811-8. 2005
    ..We assessed the expression of these putative intestinal epithelial-specific transcription factors and their influence on patient outcome...
  20. ncbi request reprint Notch inhibits Ptf1 function and acinar cell differentiation in developing mouse and zebrafish pancreas
    Farzad Esni
    Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Development 131:4213-24. 2004
    ..These results define a normal inhibitory role for Notch in the regulation of exocrine pancreatic differentiation...
  21. pmc Core signaling pathways in human pancreatic cancers revealed by global genomic analyses
    Sian Jones
    Sol Goldman Pancreatic Cancer Research Center, Ludwig Center and Howard Hughes Medical Institute at the Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA
    Science 321:1801-6. 2008
    ..Dysregulation of these core pathways and processes through mutation can explain the major features of pancreatic tumorigenesis...
  22. ncbi request reprint Notch mediates TGF alpha-induced changes in epithelial differentiation during pancreatic tumorigenesis
    Yoshiharu Miyamoto
    Departments of Surgery, Oncology, and Pathology, The Sidney Kimmel Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Cancer Cell 3:565-76. 2003
    ..These findings suggest that Notch mediates the tumor-initiating effects of TG alpha by expanding a population of undifferentiated precursor cells...
  23. ncbi request reprint Differential requirement for ptf1a in endocrine and exocrine lineages of developing zebrafish pancreas
    John W Lin
    Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA
    Dev Biol 274:491-503. 2004
    ..Together, these findings suggest the presence of distinct ptf1a-dependent and ptf1a-independent precursor populations in developing zebrafish pancreas...
  24. ncbi request reprint Predicting resectability of periampullary cancer with three-dimensional computed tomography
    Michael G House
    Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
    J Gastrointest Surg 8:280-8. 2004
    ....
  25. ncbi request reprint Gene expression profiles in pancreatic intraepithelial neoplasia reflect the effects of Hedgehog signaling on pancreatic ductal epithelial cells
    Nijaguna B Prasad
    Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
    Cancer Res 65:1619-26. 2005
    ..These data show frequent up-regulation of foregut markers in early PanIN lesions and suggest that PanIN development may involve Hedgehog-mediated conversion to a gastric epithelial differentiation program...
  26. doi request reprint Zebrafish models for cancer
    Shu Liu
    Department of Surgery, McKusick Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Annu Rev Pathol 6:71-93. 2011
    ....
  27. ncbi request reprint The role of PET scanning in pancreatic cancer
    Oscar K Serrano
    Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Hospital, 733 North Broadway, Baltimore, MD 21205, USA
    Adv Surg 44:313-25. 2010
    ....
  28. pmc Interactions between hairy/enhancer of split-related proteins and the pancreatic transcription factor Ptf1-p48 modulate function of the PTF1 transcriptional complex
    Bidyut Ghosh
    Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Biochem J 393:679-85. 2006
    ....
  29. pmc Targeted ablation of beta cells in the embryonic zebrafish pancreas using E. coli nitroreductase
    Harshan Pisharath
    Department of Comparative Medicine, Johns Hopkins School of Medicine, 720 Rutland Avenue, Ross 771, Baltimore, MD 21205, USA
    Mech Dev 124:218-29. 2007
    ....
  30. ncbi request reprint Origin of exocrine pancreatic cells from nestin-positive precursors in developing mouse pancreas
    Farzad Esni
    Department of Surgery, Johns Hopkins University School of Medicine, 600 N Wolfe St Osler 603, Baltimore, MD 21287, USA
    Mech Dev 121:15-25. 2004
    ..As in neural tissue, nestin-positive cells act as epithelial progenitors during pancreatic development, and may be regulated by EGF receptor activity...
  31. pmc Efficient drug screening and gene correction for treating liver disease using patient-specific stem cells
    Su Mi Choi
    Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Hepatology 57:2458-68. 2013
    ....
  32. pmc Multiple ribosomal proteins are expressed at high levels in developing zebrafish endoderm and are required for normal exocrine pancreas development
    Elayne Provost
    Department of Surgery, Johns Hopkins University, Baltimore, MD 21205, USA
    Zebrafish 10:161-9. 2013
    ....
  33. pmc Disputed paternity: the uncertain ancestry of pancreatic ductal neoplasia
    Anirban Maitra
    Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA
    Cancer Cell 22:701-3. 2012
    ..Whereas a rare ductal subpopulation may still prove capable of neoplastic transformation, these findings refocus attention on acinar and other non-ductal cell types as initiators of this deadly neoplasm...
  34. ncbi request reprint A histological survey of green fluorescent protein expression in 'green' mice: implications for stem cell research
    Sandra A Biankin
    Epithelial Stem Cell Working Group, Department of Surgery, Sidney Kimmel Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, USA
    Pathology 39:247-51. 2007
    ..Our aim was to investigate this assumed ubiquitous expression by performing a detailed histological survey of EGFP expression in these mice...
  35. ncbi request reprint Epithelial differentiation in pancreatic development and neoplasia: new niches for nestin and Notch
    Steven D Leach
    Department of Surgery and Oncology, Johns Hopkins University, Baltimore, MD 21205, USA
    J Clin Gastroenterol 39:S78-82. 2005
    ..In this review, we summarize recent studies involving regulation of epithelial differentiation in both embryonic and adult pancreas and highlight the role of Notch in regulating an exocrine progenitor pool...
  36. pmc Results of pancreaticoduodenectomy for lymphoplasmacytic sclerosing pancreatitis
    Jeffrey M Hardacre
    Department of Surgery, The Johns Hopkins Hospital, 600 N Wolfe Street, Baltimore, MD 21287 4688, USA
    Ann Surg 237:853-8; discussion 858-9. 2003
    ....
  37. ncbi request reprint Characterization of gene expression in mucinous cystic neoplasms of the pancreas using oligonucleotide microarrays
    Noriyoshi Fukushima
    Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA
    Oncogene 23:9042-51. 2004
    ..Some of the genes identified as overexpressed in these neoplasms may be useful as markers that can distinguish MCNs from non-neoplastic pancreatic cystic lesions...
  38. ncbi request reprint Primary explant cultures of adult and embryonic pancreas
    Farzad Esni
    Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Methods Mol Med 103:259-71. 2005
    ..These methods may be utilized in studies involving normal epithelial differentiation, contributing to improved understanding of pancreatic development and disease...
  39. ncbi request reprint Pancreatic epithelial plasticity mediated by acinar cell transdifferentiation and generation of nestin-positive intermediates
    Anna L Means
    Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Development 132:3767-76. 2005
    ....
  40. ncbi request reprint Pancreatic cancer
    Theresa Pluth Yeo
    Departments of Surgery, Oncology, Pathology and Medicine Johns Hopkins Medical Institutions Baltimore, Maryland, USA
    Curr Probl Cancer 26:176-275. 2002
  41. ncbi request reprint A case of mistaken identity? Nonductal origins of pancreatic "ductal" cancers
    L Charles Murtaugh
    Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA
    Cancer Cell 11:211-3. 2007
    ..The results shed new light on the "cell of origin" of pancreatic ductal cancer and demonstrate that chronic pancreatitis provides a permissive environment for Kras-induced pancreatic neoplasia...
  42. ncbi request reprint Notch in malignancy
    Douglas W Ball
    Cancer Treat Res 115:95-121. 2003
  43. ncbi request reprint Overexpression of heparin-binding EGF-like growth factor in mouse pancreas results in fibrosis and epithelial metaplasia
    Anna L Means
    Department of Surgical Sciences, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    Gastroenterology 124:1020-36. 2003
    ..This report examines the effects of HB-EGF overexpression in mouse pancreas...
  44. pmc Matrix metalloproteinase-7 is expressed by pancreatic cancer precursors and regulates acinar-to-ductal metaplasia in exocrine pancreas
    Howard C Crawford
    Department of Cancer Biology, Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA
    J Clin Invest 109:1437-44. 2002
    ..Thus, MMP-7 and FasL influence the initiation and maintenance of metaplastic events in pancreatic epithelium, explaining the observed link between metaplasia and apoptosis in pancreas and other gastrointestinal tissues...
  45. ncbi request reprint Evidence for repatterning of the gastric fundic epithelium associated with Ménétrier's disease and TGFalpha overexpression
    Sachiyo Nomura
    Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 2733, USA
    Gastroenterology 128:1292-305. 2005
    ....
  46. pmc Graded levels of Ptf1a differentially regulate endocrine and exocrine fates in the developing pancreas
    P Duc Si Dong
    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94158, USA
    Genes Dev 22:1445-50. 2008
    ..We propose that low levels of Ptf1a promote endocrine fate, whereas high levels repress endocrine fate and promote exocrine fate...
  47. ncbi request reprint Differential ability of Ptf1a and Ptf1a-VP16 to convert stomach, duodenum and liver to pancreas
    Zeina H Jarikji
    Laboratory of Molecular Organogenesis, Institut de Recherches Cliniques de Montreal, 110 Pine Avenue West, Montreal, QC, Canada H2W 1R7
    Dev Biol 304:786-99. 2007
    ..Lastly, we demonstrate that, similar to mouse and zebrafish, Xenopus Ptf1a is essential for the initial specification of both endocrine and exocrine cells during normal pancreas development...
  48. pmc Preexisting pancreatic acinar cells contribute to acinar cell, but not islet beta cell, regeneration
    Biva M Desai
    Division of Endocrinology, Diabetes, and Metabolism and Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    J Clin Invest 117:971-7. 2007
    ..These results indicate that mature acinar cells harbor a facultative acinar but not endocrine progenitor capacity...
  49. ncbi request reprint Nonapical symmetric divisions underlie horizontal cell layer formation in the developing retina in vivo
    Leanne Godinho
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, MO 63110, USA
    Neuron 56:597-603. 2007
    ..We have thus identified a dedicated HC precursor, and our findings suggest a mechanism of neuronal layer formation whereby the location of mitosis could facilitate rapid contact between synaptic partners...
  50. ncbi request reprint Metaplastic metamorphoses in the mammalian pancreas
    Stephen F Konieczny
    Gastroenterology 133:2056-9. 2007
  51. ncbi request reprint Transgenic overexpression of amphiregulin induces a mitogenic response selectively in pancreatic duct cells
    Martin Wagner
    Department of Internal Medicine I, University of Ulm, Germany
    Gastroenterology 122:1898-912. 2002
    ....

Research Grants2

  1. Centroacinar progenitors in mouse and zebrafish pancreas
    Steven D Leach; Fiscal Year: 2010
    ..This project will characterize a novel population of progenitor cells in mouse and zebra fish pancreas, in hopes that they will provide a renewable resource for replacement b-cells. ..
  2. Regulation of Exocrine Pancreatic Progenitors by Ptf1a-p48
    Steven D Leach; Fiscal Year: 2010
    ....