Research Topics
Genomes and Genes
| Steven D LeachSummaryAffiliation: Johns Hopkins University Country: USA Publications
Research Grants
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Detail Information
Publications
Wnt/beta-catenin signaling is required for development of the exocrine pancreasJames 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...
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....- Oncogenic KRAS induces progenitor cell expansion and malignant transformation in zebrafish exocrine pancreasSeung 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... - Hedgehog signaling is required for effective regeneration of exocrine pancreasVolker 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... - Ribosomal biogenesis genes play an essential and p53-independent role in zebrafish pancreas developmentElayne 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... 
Characterization of Kras-mediated pancreatic tumorigenesis in zebrafishJon M Davison
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Methods Enzymol 438:391-417. 2008....- Gene expression alterations in the non-neoplastic parenchyma adjacent to infiltrating pancreatic ductal adenocarcinomaNoriyoshi Fukushima
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD 21205-2196, USA
Mod Pathol 18:779-87. 2005.... - Repression of the miR-143/145 cluster by oncogenic Ras initiates a tumor-promoting feed-forward pathwayOliver 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... - Notch-responsive cells initiate the secondary transition in larval zebrafish pancreasMichael 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... - Screening pancreatic oncogenes in zebrafish using the Gal4/UAS systemShu 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... - Spontaneous induction of murine pancreatic intraepithelial neoplasia (mPanIN) by acinar cell targeting of oncogenic Kras in adult miceNils 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.... - In vivo imaging of zebrafish digestive organ function using multiple quenched fluorescent reportersKotaro 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... - Gal4/UAS transgenic tools and their application to zebrafishMarnie 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... - Isolation and characterization of centroacinar/terminal ductal progenitor cells in adult mouse pancreasMeritxell 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... - Transactivation from Gal4-VP16 transgenic insertions for tissue-specific cell labeling and ablation in zebrafishJon M Davison
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Dev Biol 304:811-24. 2007.... - Viral 2A peptides allow expression of multiple proteins from a single ORF in transgenic zebrafish embryosElayne 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... - Differential requirement for ptf1a in endocrine and exocrine lineages of developing zebrafish pancreasJohn 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... - Expression of the caudal-type homeodomain transcription factors CDX 1/2 and outcome in carcinomas of the ampulla of VaterDonna 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... - Notch inhibits Ptf1 function and acinar cell differentiation in developing mouse and zebrafish pancreasFarzad 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... - Core signaling pathways in human pancreatic cancers revealed by global genomic analysesSian 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... - Notch mediates TGF alpha-induced changes in epithelial differentiation during pancreatic tumorigenesisYoshiharu 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... - Predicting resectability of periampullary cancer with three-dimensional computed tomographyMichael G House
Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
J Gastrointest Surg 8:280-8. 2004.... - Differential requirement for ptf1a in endocrine and exocrine lineages of developing zebrafish pancreasJohn 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... - Targeted ablation of beta cells in the embryonic zebrafish pancreas using E. coli nitroreductaseHarshan 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.... - Gene expression profiles in pancreatic intraepithelial neoplasia reflect the effects of Hedgehog signaling on pancreatic ductal epithelial cellsNijaguna 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... - The role of PET scanning in pancreatic cancerOscar 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.... - Interactions between hairy/enhancer of split-related proteins and the pancreatic transcription factor Ptf1-p48 modulate function of the PTF1 transcriptional complexBidyut Ghosh
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Biochem J 393:679-85. 2006.... - Zebrafish models for cancerShu 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.... - Origin of exocrine pancreatic cells from nestin-positive precursors in developing mouse pancreasFarzad 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... - Disputed paternity: the uncertain ancestry of pancreatic ductal neoplasiaAnirban 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... - A histological survey of green fluorescent protein expression in 'green' mice: implications for stem cell researchSandra 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... - Epithelial differentiation in pancreatic development and neoplasia: new niches for nestin and NotchSteven 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... - Results of pancreaticoduodenectomy for lymphoplasmacytic sclerosing pancreatitisJeffrey 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..Nevertheless, differentiation from pancreatic neoplasia remains difficult. Patients undergoing pancreaticoduodenectomy for LPSP have durable relief of symptoms and a subjectively improved quality of life... - Characterization of gene expression in mucinous cystic neoplasms of the pancreas using oligonucleotide microarraysNoriyoshi 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... - Primary explant cultures of adult and embryonic pancreasFarzad 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... - Pancreatic cancerTheresa Pluth Yeo
Departments of Surgery, Oncology, Pathology and Medicine Johns Hopkins Medical Institutions Baltimore, Maryland, USA
Curr Probl Cancer 26:176-275. 2002 - A case of mistaken identity? Nonductal origins of pancreatic "ductal" cancersL 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... - Pancreatic epithelial plasticity mediated by acinar cell transdifferentiation and generation of nestin-positive intermediatesAnna L Means
Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
Development 132:3767-76. 2005.... - Metaplastic metamorphoses in the mammalian pancreasStephen F Konieczny
Gastroenterology 133:2056-9. 2007 - Notch in malignancyDouglas W Ball
Cancer Treat Res 115:95-121. 2003 - Overexpression of heparin-binding EGF-like growth factor in mouse pancreas results in fibrosis and epithelial metaplasiaAnna 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... - Matrix metalloproteinase-7 is expressed by pancreatic cancer precursors and regulates acinar-to-ductal metaplasia in exocrine pancreasHoward 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... - Differential ability of Ptf1a and Ptf1a-VP16 to convert stomach, duodenum and liver to pancreasZeina 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... - Evidence for repatterning of the gastric fundic epithelium associated with Ménétrier's disease and TGFalpha overexpressionSachiyo Nomura
Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 2733, USA
Gastroenterology 128:1292-305. 2005.... - Preexisting pancreatic acinar cells contribute to acinar cell, but not islet beta cell, regenerationBiva 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... - Nonapical symmetric divisions underlie horizontal cell layer formation in the developing retina in vivoLeanne 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... - Graded levels of Ptf1a differentially regulate endocrine and exocrine fates in the developing pancreasP 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... - Transgenic overexpression of amphiregulin induces a mitogenic response selectively in pancreatic duct cellsMartin Wagner
Department of Internal Medicine I, University of Ulm, Germany
Gastroenterology 122:1898-912. 2002....
Research Grants
- Centroacinar progenitors in mouse and zebrafish pancreasSteven 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. ..
- Regulation of Exocrine Pancreatic Progenitors by Ptf1a-p48Steven D Leach; Fiscal Year: 2010....