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Matthias Hebrok, PhD

TitleProfessor
SchoolUCSF School of Medicine
DepartmentDiabetes Center
Address513 Parnassus Ave
San Francisco CA 94143
Phone415-514-0820
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    Other Positions
    TitleDirector, Diabetes Center


    Collapse Overview 
    Collapse Overview
    The main focus of my lab is to understand how islets of Langerhans, the endocrine component of the pancreas, are formed during organogenesis, how their function is regulated in the mature organism, and how changes in gene expression might allow islet regeneration. Islet cells, including glucagon-producing a- and insulin-producing ß-cells, regulate blood glucose homeostasis. The importance of the latter is highlighted by the fact that loss of ß-cells leads to type I diabetes mellitus. Conventional treatment of diabetic patients is based on insulin injections. Unfortunately, episodes of hypo- and hyperglycemia occur frequently and result in severe secondary complications, including coronary and microvascular diseases. Recent reports have shown that islet transplantation successfully restores glucose tolerance. However islets are in short supply, a dilemma that severely restricts the feasibility of large-scale therapy through islet transplantation. An alternative approach is the regeneration of ß- or islet cells from committed precursor cells and the majority of the projects in my lab are designed to unravel the program that directs an ordinary cell in the gut to become a ß-cell. Understanding of these processes will be crucial for future cell replacement strategies.

    Analysis of known signaling pathways: We employ knockout and transgenic mice lines to study the effect of known signaling pathways involved in cell proliferation, differentiation and migration on islet progenitor cells. In particular, we are interested in understanding how components of the Hedgehog and Wnt pathways influence pancreas development and endocrine cell differentiation. While previous studies have suggested an inhibitory role for members of the Hedgehog family, our recent results indicate that some Hedgehog signaling is required for pancreas formation. Currently, we are using a combination of knockout and transgenic approaches to determine if manipulations of the Hedgehog and Wnt pathways stimulate ß-cell development and function.

    Identification of novel pancreas/islet genes: In another set of experiments we have identified novel pancreatic genes via 'gene-trapping'. This technique allows to randomly trap and mark genes by inserting a target construct containing the bacterial LacZ gene into the DNA of embryonic stem (ES) cells. Trapped genes are identified by sequencing of amplified cDNA fragments (5' RACE) and mouse lines are established by blastocyst injection. The insertion of the gene-trap vector places the bacterial ß-galactosidase gene under control of the promoter of the trapped gene. Thus, the normal expression pattern of this gene can rapidly be visualized by staining for ß-galactosidase activity within any given tissue, including the pancreas. More importantly, vector insertion causes either null or severe hypomorphic mutations that reveal if the trapped gene is essential for pancreas and ß-cell differentiation. These studies are done in collaboration with Marc Tessier-Lavigne, Stanford University, who is interested in brain development and is generously providing mice for our analysis.

    Generation of ß-cells from adult progenitor cells: Recent studies have shown that adult organ stem cells have the ability to develop into a number of different tissues. We are taking advantage of our understanding of pancreas development and have started to investigate if adult progenitor cells have the potential to develop into insulin-producing ß-cells. Bone marrow derived stem cells are co-cultured with embryonic pancreas buds that develop into endocrine islets and thus provide the necessary signals for ß-cell differentiation. Initially, we focus on murine adult stem cells, but will include human cells as soon as the 'proof of principle' experiments have shown that murine cells can adopt pancreatic fates.

    Model systems for pancreatic cancer: Overt hedgehog signaling has been implicated in cancer formation in various tissues; however it has not been linked to the formation of pancreatic adenocarcinomas, an aggressive form of cancer that is virtually incurable. We have started collaboration with Martin McMahon's laboratory at the UCSF Cancer Center to show that deregulated Hedgehog signaling promotes proliferation of pancreatic cancer cell lines and if inhibition of Hedgehog signaling blocks cell proliferation. Currently, we are manipulating the Hedgehog pathway in pancreatic tissue of transgenic animals to address the tumorigenic activity of this pathway in vivo.


    Collapse Research 
    Collapse Research Activities and Funding
    Using human stem cell-derived thymic epithelium to remodel T1D immune tolerance
    NIH/NIDDK R01DK107383Jul 1, 2016 - Jun 30, 2020
    Role: Co-Principal Investigator
    Using human stem cell-derived thymic epithelium to remodel T1D immune tolerance
    NIH/NIDDK U01DK107383Jul 1, 2016 - Jun 30, 2020
    Role: Co-Principal Investigator
    Mechanisms of beta cell maturation
    NIH/NIDDK R01DK108666Sep 30, 2015 - Jul 31, 2019
    Role: Principal Investigator
    Regulation of beta cell identity and dedifferentiation
    NIH/NIDDK R01DK105831May 1, 2015 - Apr 30, 2019
    Role: Principal Investigator
    Epigenetic regulation of pancreatic cancer
    NIH/NCI R01CA172045Apr 3, 2014 - Feb 28, 2019
    Role: Principal Investigator
    Defining the role of MafA in islet beta cells
    NIH/NIDDK R01DK090570Jul 29, 2011 - Jun 30, 2020
    Role: Co-Principal Investigator
    "Expanding beta-cell mass"
    NIH/NIDDK U01DK089541Sep 15, 2010 - Jun 30, 2015
    Role: Co-Principal Investigator
    Embryonic signaling pathways in pancreatic cancer
    NIH/NCI R01CA112537Sep 1, 2004 - Nov 30, 2015
    Role: Principal Investigator
    Diabetes Research Center
    NIH/NIDDK P30DK063720Sep 1, 2002 - Mar 31, 2020
    Role: Co-Investigator
    Effects of Hedgehog Signaling on Pancreas Organogenesis
    NIH/NIDDK R01DK060533Dec 1, 2001 - Feb 28, 2014
    Role: Principal Investigator
    Molecular Control of Pancreatic Islet Development
    NIH/NIDDK U19DK061245Sep 30, 2001 - Jul 31, 2006
    Role: Co-Investigator

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    Collapse In The News
    Collapse Global Health

    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
    List All   |   Timeline
    1. Faleo G, Russ HA, Wisel S, Parent AV, Nguyen V, Nair GG, Freise JE, Villanueva KE, Szot GL, Hebrok M, Tang Q. Mitigating Ischemic Injury of Stem Cell-Derived Insulin-Producing Cells after Transplant. Stem Cell Reports. 2017 Aug 08. PMID: 28803916.
      View in: PubMed
    2. Chang R, Faleo G, Russ HA, Parent AV, Elledge SK, Bernards DA, Allen JL, Villanueva K, Hebrok M, Tang Q, Desai TA. Nanoporous Immunoprotective Device for Stem-Cell-Derived ß-Cell Replacement Therapy. ACS Nano. 2017 Aug 07. PMID: 28763191.
      View in: PubMed
    3. von Figura G, Fahrenkrog-Petersen L, Hidalgo-Sastre A, Hartmann D, Hüser N, Schmid RM, Hebrok M, Roy N, Esposito I. Atypical flat lesions derive from pancreatic acinar cells. Pancreatology. 2017 May - Jun; 17(3):350-353. PMID: 28473229.
      View in: PubMed
    4. Ivry SL, Sharib JM, Dominguez DA, Roy N, Hatcher SE, Yip-Schneider M, Schmidt CM, Brand RE, Park WG, Hebrok M, Kim G, O'Donoghue AJ, Kirkwood KS, Craik CS. Global protease activity profiling provides differential diagnosis of pancreatic cysts. Clin Cancer Res. 2017 Apr 19. PMID: 28424202.
      View in: PubMed
    5. Hebrok M. Designing ß Cells. Cell Metab. 2017 02 07; 25(2):223-224. PMID: 28178560.
      View in: PubMed
    6. Liu JS, Hebrok M. All mixed up: defining roles for ß-cell subtypes in mature islets. Genes Dev. 2017 Feb 01; 31(3):228-240. PMID: 28270515.
      View in: PubMed
    7. Roy N, Takeuchi KK, Ruggeri JM, Bailey P, Chang D, Li J, Leonhardt L, Puri S, Hoffman MT, Gao S, Halbrook CJ, Song Y, Ljungman M, Malik S, Wright CV, Dawson DW, Biankin AV, Hebrok M, Crawford HC. PDX1 dynamically regulates pancreatic ductal adenocarcinoma initiation and maintenance. Genes Dev. 2016 Dec 15; 30(24):2669-2683. PMID: 28087712.
      View in: PubMed
    8. Bonifacio E, Mathieu C, Nepom GT, Ziegler AG, Anhalt H, Haller MJ, Harrison LC, Hebrok M, Kushner JA, Norris JM, Peakman M, Powers AC, Todd JA, Atkinson MA. Rebranding asymptomatic type 1 diabetes: the case for autoimmune beta cell disorder as a pathological and diagnostic entity. Diabetologia. 2016 Oct 26. PMID: 27785529.
      View in: PubMed
    9. Muñoz-Bravo JL, Flores-Martínez A, Herrero-Martin G, Puri S, Taketo MM, Rojas A, Hebrok M, Cano DA. Loss of Pancreas upon Activated Wnt Signaling Is Concomitant with Emergence of Gastrointestinal Identity. PLoS One. 2016; 11(10):e0164714. PMID: 27736991.
      View in: PubMed
    10. Dorrell C, Schug J, Canaday PS, Russ HA, Tarlow BD, Grompe MT, Horton T, Hebrok M, Streeter PR, Kaestner KH, Grompe M. Human islets contain four distinct subtypes of ß cells. Nat Commun. 2016; 7:11756. PMID: 27399229.
      View in: PubMed
    11. Laklai H, Miroshnikova YA, Pickup MW, Collisson EA, Kim GE, Barrett AS, Hill RC, Lakins JN, Schlaepfer DD, Mouw JK, LeBleu VS, Roy N, Novitskiy SV, Johansen JS, Poli V, Kalluri R, Iacobuzio-Donahue CA, Wood LD, Hebrok M, Hansen K, Moses HL, Weaver VM. Genotype tunes pancreatic ductal adenocarcinoma tissue tension to induce matricellular fibrosis and tumor progression. Nat Med. 2016 May; 22(5):497-505. PMID: 27089513.
      View in: PubMed
    12. Hendley AM, Wang YJ, Polireddy K, Alsina J, Ahmed I, Lafaro KJ, Zhang H, Roy N, Savidge SG, Cao Y, Hebrok M, Maitra A, Reynolds A, Goggins MG, Younes M, Iacobuzio-Donahue CA, Leach SD, Bailey J. p120 Catenin Suppresses Basal Epithelial Cell Extrusion in Invasive Pancreatic Neoplasia. Cancer Res. 2016 Jun 1; 76(11):3351-63. PMID: 27032419.
      View in: PubMed
    13. Wilcox NS, Rui J, Hebrok M, Herold KC. Life and death of ß cells in Type 1 diabetes: A comprehensive review. J Autoimmun. 2016 Jul; 71:51-8. PMID: 27017348.
      View in: PubMed
    14. Saini C, Petrenko V, Pulimeno P, Giovannoni L, Berney T, Hebrok M, Howald C, Dermitzakis ET, Dibner C. A functional circadian clock is required for proper insulin secretion by human pancreatic islet cells. Diabetes Obes Metab. 2016 Apr; 18(4):355-65. PMID: 26662378.
      View in: PubMed
    15. Zhu S, Russ HA, Wang X, Zhang M, Ma T, Xu T, Tang S, Hebrok M, Ding S. Human pancreatic beta-like cells converted from fibroblasts. Nat Commun. 2016; 7:10080. PMID: 26733021.
      View in: PubMed
    16. Roy N, Hebrok M. Regulation of Cellular Identity in Cancer. Dev Cell. 2015 Dec 21; 35(6):674-84. PMID: 26702828.
      View in: PubMed
    17. Suriben R, Kaihara KA, Paolino M, Reichelt M, Kummerfeld SK, Modrusan Z, Dugger DL, Newton K, Sagolla M, Webster JD, Liu J, Hebrok M, Dixit VM. ß-Cell Insulin Secretion Requires the Ubiquitin Ligase COP1. Cell. 2015 Dec 3; 163(6):1457-67. PMID: 26627735.
      View in: PubMed
    18. Russ HA, Landsman L, Moss CL, Higdon R, Greer RL, Kaihara K, Salamon R, Kolker E, Hebrok M. Dynamic Proteomic Analysis of Pancreatic Mesenchyme Reveals Novel Factors That Enhance Human Embryonic Stem Cell to Pancreatic Cell Differentiation. Stem Cells Int. 2016; 2016:6183562. PMID: 26681951.
      View in: PubMed
    19. Zdravkovic T, Nazor KL, Larocque N, Gormley M, Donne M, Hunkapillar N, Giritharan G, Bernstein HS, Wei G, Hebrok M, Zeng X, Genbacev O, Mattis A, McMaster MT, Krtolica A, Valbuena D, Simón C, Laurent LC, Loring JF, Fisher SJ. Human stem cells from single blastomeres reveal pathways of embryonic or trophoblast fate specification. Development. 2015 Dec 1; 142(23):4010-25. PMID: 26483210.
      View in: PubMed
    20. Dhawan S, Tschen SI, Zeng C, Guo T, Hebrok M, Matveyenko A, Bhushan A. DNA methylation directs functional maturation of pancreatic ß cells. J Clin Invest. 2015 Jul 1; 125(7):2851-60. PMID: 26098213; PMCID: PMC4563682.
    21. Russ HA, Parent AV, Ringler JJ, Hennings TG, Nair GG, Shveygert M, Guo T, Puri S, Haataja L, Cirulli V, Blelloch R, Szot GL, Arvan P, Hebrok M. Controlled induction of human pancreatic progenitors produces functional beta-like cells in vitro. EMBO J. 2015 Jul 2; 34(13):1759-72. PMID: 25908839; PMCID: PMC4516429 [Available on 07/02/16].
    22. Nair G, Hebrok M. Islet formation in mice and men: lessons for the generation of functional insulin-producing ß-cells from human pluripotent stem cells. Curr Opin Genet Dev. 2015 Jun; 32:171-80. PMID: 25909383; PMCID: PMC4523641 [Available on 06/01/16].
    23. Roy N, Malik S, Villanueva KE, Urano A, Lu X, Von Figura G, Seeley ES, Dawson DW, Collisson EA, Hebrok M. Brg1 promotes both tumor-suppressive and oncogenic activities at distinct stages of pancreatic cancer formation. Genes Dev. 2015 Mar 15; 29(6):658-71. PMID: 25792600; PMCID: PMC4378197.
    24. Huskey NE, Guo T, Evason KJ, Momcilovic O, Pardo D, Creasman KJ, Judson RL, Blelloch R, Oakes SA, Hebrok M, Goga A. CDK1 inhibition targets the p53-NOXA-MCL1 axis, selectively kills embryonic stem cells, and prevents teratoma formation. Stem Cell Reports. 2015 Mar 10; 4(3):374-89. PMID: 25733019; PMCID: PMC4375943.
    25. Chen NM, Singh G, Koenig A, Liou GY, Storz P, Zhang JS, Regul L, Nagarajan S, Kühnemuth B, Johnsen SA, Hebrok M, Siveke J, Billadeau DD, Ellenrieder V, Hessmann E. NFATc1 Links EGFR Signaling to Induction of Sox9 Transcription and Acinar-Ductal Transdifferentiation in the Pancreas. Gastroenterology. 2015 May; 148(5):1024-1034.e9. PMID: 25623042; PMCID: PMC4409493 [Available on 05/01/16].
    26. Singh SK, Chen NM, Hessmann E, Siveke J, Lahmann M, Singh G, Voelker N, Vogt S, Esposito I, Schmidt A, Brendel C, Stiewe T, Gaedcke J, Mernberger M, Crawford HC, Bamlet WR, Zhang JS, Li XK, Smyrk TC, Billadeau DD, Hebrok M, Neesse A, Koenig A, Ellenrieder V. Antithetical NFATc1-Sox2 and p53-miR200 signaling networks govern pancreatic cancer cell plasticity. EMBO J. 2015 Feb 12; 34(4):517-30. PMID: 25586376; PMCID: PMC4331005 [Available on 02/12/16].
    27. Puri S, Folias AE, Hebrok M. Plasticity and dedifferentiation within the pancreas: development, homeostasis, and disease. Cell Stem Cell. 2015 Jan 8; 16(1):18-31. PMID: 25465113; PMCID: PMC4289422 [Available on 01/08/16].
    28. Russ HA, Hebrok M. Taming the young and restless--epigenetic gene regulation in pancreas and beta-cell precursors. EMBO J. 2014 Oct 1; 33(19):2135-6. PMID: 25154606; PMCID: PMC4282500.
    29. Folias AE, Penaranda C, Su AL, Bluestone JA, Hebrok M. Aberrant innate immune activation following tissue injury impairs pancreatic regeneration. PLoS One. 2014; 9(7):e102125. PMID: 25010227; PMCID: PMC4092101.
    30. Morris JP, Greer R, Russ HA, von Figura G, Kim GE, Busch A, Lee J, Hertel KJ, Kim S, McManus M, Hebrok M. Dicer regulates differentiation and viability during mouse pancreatic cancer initiation. PLoS One. 2014; 9(5):e95486. PMID: 24788257; PMCID: PMC4006805.
    31. Folias AE, Hebrok M. Diabetes. Solving human ß-cell development--what does the mouse say? Nat Rev Endocrinol. 2014 May; 10(5):253-5. PMID: 24566816.
      View in: PubMed
    32. von Figura G, Fukuda A, Roy N, Liku ME, Morris Iv JP, Kim GE, Russ HA, Firpo MA, Mulvihill SJ, Dawson DW, Ferrer J, Mueller WF, Busch A, Hertel KJ, Hebrok M. The chromatin regulator Brg1 suppresses formation of intraductal papillary mucinous neoplasm and pancreatic ductal adenocarcinoma. Nat Cell Biol. 2014 Mar; 16(3):255-67. PMID: 24561622.
      View in: PubMed
    33. Li K, Zhu S, Russ HA, Xu S, Xu T, Zhang Y, Ma T, Hebrok M, Ding S. Small molecules facilitate the reprogramming of mouse fibroblasts into pancreatic lineages. Cell Stem Cell. 2014 Feb 6; 14(2):228-36. PMID: 24506886.
      View in: PubMed
    34. Puri S, Akiyama H, Hebrok M. VHL-mediated disruption of Sox9 activity compromises ß-cell identity and results in diabetes mellitus. Genes Dev. 2013 Dec 1; 27(23):2563-75. PMID: 24298056; PMCID: PMC3861670.
    35. Puri S, García-Núñez A, Hebrok M, Cano DA. Elimination of von Hippel-Lindau function perturbs pancreas endocrine homeostasis in mice. PLoS One. 2013; 8(8):e72213. PMID: 23977255; PMCID: PMC3748057.
    36. Greer RL, Staley BK, Liou A, Hebrok M. Numb regulates acinar cell dedifferentiation and survival during pancreatic damage and acinar-to-ductal metaplasia. Gastroenterology. 2013 Nov; 145(5):1088-1097.e8. PMID: 23891977; PMCID: PMC3805717.
    37. Zhang Y, Morris JP, Yan W, Schofield HK, Gurney A, Simeone DM, Millar SE, Hoey T, Hebrok M, Pasca di Magliano M. Canonical wnt signaling is required for pancreatic carcinogenesis. Cancer Res. 2013 Aug 1; 73(15):4909-22. PMID: 23761328; PMCID: PMC3763696.
    38. Stanger BZ, Hebrok M. Control of cell identity in pancreas development and regeneration. Gastroenterology. 2013 Jun; 144(6):1170-9. PMID: 23622126; PMCID: PMC3639438.
    39. Parent AV, Russ HA, Khan IS, LaFlam TN, Metzger TC, Anderson MS, Hebrok M. Generation of functional thymic epithelium from human embryonic stem cells that supports host T cell development. Cell Stem Cell. 2013 Aug 1; 13(2):219-29. PMID: 23684540; PMCID: PMC3869399.
    40. von Figura G, Morris JP, Wright CV, Hebrok M. Nr5a2 maintains acinar cell differentiation and constrains oncogenic Kras-mediated pancreatic neoplastic initiation. Gut. 2014 Apr; 63(4):656-64. PMID: 23645620; PMCID: PMC3883808.
    41. Lin WC, Rajbhandari N, Liu C, Sakamoto K, Zhang Q, Triplett AA, Batra SK, Opavsky R, Felsher DW, DiMaio DJ, Hollingsworth MA, Morris JP, Hebrok M, Witkiewicz AK, Brody JR, Rui H, Wagner KU. Dormant cancer cells contribute to residual disease in a model of reversible pancreatic cancer. Cancer Res. 2013 Mar 15; 73(6):1821-30. PMID: 23467612; PMCID: PMC3602120.
    42. Guo T, Landsman L, Li N, Hebrok M. Factors expressed by murine embryonic pancreatic mesenchyme enhance generation of insulin-producing cells from hESCs. Diabetes. 2013 May; 62(5):1581-92. PMID: 23305648; PMCID: PMC3636645.
    43. Kopp JL, von Figura G, Mayes E, Liu FF, Dubois CL, Morris JP, Pan FC, Akiyama H, Wright CV, Jensen K, Hebrok M, Sander M. Identification of Sox9-dependent acinar-to-ductal reprogramming as the principal mechanism for initiation of pancreatic ductal adenocarcinoma. Cancer Cell. 2012 Dec 11; 22(6):737-50. PMID: 23201164; PMCID: PMC3568632.
    44. Pasca di Magliano M, Forsmark C, Freedman S, Hebrok M, Pasricha PJ, Saluja A, Stanger BZ, Holt J, Serrano J, James SP, Rustgi AK. Advances in acute and chronic pancreatitis: from development to inflammation and repair. Gastroenterology. 2013 Jan; 144(1):e1-4. PMID: 23159450; PMCID: PMC4096699.
    45. Puri S, Hebrok M. Diabetic ß Cells: To Be or Not To Be? Cell. 2012 Sep 14; 150(6):1103-4. PMID: 22980973.
      View in: PubMed
    46. Hebrok M. Generating ß cells from stem cells-the story so far. Cold Spring Harb Perspect Med. 2012 Jun; 2(6):a007674. PMID: 22675664; PMCID: PMC3367541.
    47. Fukuda A, Morris JP, Hebrok M. Bmi1 is required for regeneration of the exocrine pancreas in mice. Gastroenterology. 2012 Sep; 143(3):821-31.e1-2. PMID: 22609312; PMCID: PMC3485080.
    48. Qin H, Blaschke K, Wei G, Ohi Y, Blouin L, Qi Z, Yu J, Yeh RF, Hebrok M, Ramalho-Santos M. Transcriptional analysis of pluripotency reveals the Hippo pathway as a barrier to reprogramming. Hum Mol Genet. 2012 May 1; 21(9):2054-67. PMID: 22286172; PMCID: PMC3315209.
    49. Landsman L, Parent A, Hebrok M. Elevated Hedgehog/Gli signaling causes beta-cell dedifferentiation in mice. Proc Natl Acad Sci U S A. 2011 Oct 11; 108(41):17010-5. PMID: 21969560; PMCID: PMC3193206.
    50. Landsman L, Nijagal A, Whitchurch TJ, Vanderlaan RL, Zimmer WE, Mackenzie TC, Hebrok M. Pancreatic mesenchyme regulates epithelial organogenesis throughout development. PLoS Biol. 2011 Sep; 9(9):e1001143. PMID: 21909240; PMCID: PMC3167782.
    51. Atkinson MA, Bluestone JA, Eisenbarth GS, Hebrok M, Herold KC, Accili D, Pietropaolo M, Arvan PR, Von Herrath M, Markel DS, Rhodes CJ. How does type 1 diabetes develop?: the notion of homicide or ß-cell suicide revisited. Diabetes. 2011 May; 60(5):1370-9. PMID: 21525508; PMCID: PMC3292309.
    52. Ohi Y, Qin H, Hong C, Blouin L, Polo JM, Guo T, Qi Z, Downey SL, Manos PD, Rossi DJ, Yu J, Hebrok M, Hochedlinger K, Costello JF, Song JS, Ramalho-Santos M. Incomplete DNA methylation underlies a transcriptional memory of somatic cells in human iPS cells. Nat Cell Biol. 2011 May; 13(5):541-9. PMID: 21499256; PMCID: PMC3987913.
    53. Fukuda A, Wang SC, Morris JP, Folias AE, Liou A, Kim GE, Akira S, Boucher KM, Firpo MA, Mulvihill SJ, Hebrok M. Stat3 and MMP7 contribute to pancreatic ductal adenocarcinoma initiation and progression. Cancer Cell. 2011 Apr 12; 19(4):441-55. PMID: 21481787; PMCID: PMC3075548.
    54. Morris JP, Wang SC, Hebrok M. KRAS, Hedgehog, Wnt and the twisted developmental biology of pancreatic ductal adenocarcinoma. Nat Rev Cancer. 2010 Oct; 10(10):683-95. PMID: 20814421; PMCID: PMC4085546.
    55. Kockel L, Kerr KS, Melnick M, Brückner K, Hebrok M, Perrimon N. Dynamic switch of negative feedback regulation in Drosophila Akt-TOR signaling. PLoS Genet. 2010 Jun; 6(6):e1000990. PMID: 20585550; PMCID: PMC2887466.
    56. Cervantes S, Lau J, Cano DA, Borromeo-Austin C, Hebrok M. Primary cilia regulate Gli/Hedgehog activation in pancreas. Proc Natl Acad Sci U S A. 2010 Jun 1; 107(22):10109-14. PMID: 20479231; PMCID: PMC2890485.
    57. Puri S, Hebrok M. Cellular plasticity within the pancreas--lessons learned from development. Dev Cell. 2010 Mar 16; 18(3):342-56. PMID: 20230744; PMCID: PMC4085547.
    58. Lau J, Hebrok M. Hedgehog signaling in pancreas epithelium regulates embryonic organ formation and adult beta-cell function. Diabetes. 2010 May; 59(5):1211-21. PMID: 20185815; PMCID: PMC2857901.
    59. Morris JP, Cano DA, Sekine S, Wang SC, Hebrok M. Beta-catenin blocks Kras-dependent reprogramming of acini into pancreatic cancer precursor lesions in mice. J Clin Invest. 2010 Feb; 120(2):508-20. PMID: 20071774; PMCID: PMC2810083.
    60. Morris JP, Hebrok M. It's a free for all--insulin-positive cells join the group of potential progenitors for pancreatic ductal adenocarcinoma. Cancer Cell. 2009 Nov 6; 16(5):359-61. PMID: 19878864.
      View in: PubMed
    61. Sekine S, Ogawa R, Mcmanus MT, Kanai Y, Hebrok M. Dicer is required for proper liver zonation. J Pathol. 2009 Nov; 219(3):365-72. PMID: 19718708.
      View in: PubMed
    62. Guo T, Hebrok M. Stem cells to pancreatic beta-cells: new sources for diabetes cell therapy. Endocr Rev. 2009 May; 30(3):214-27. PMID: 19389995; PMCID: PMC2726841.
    63. Sekine S, Ogawa R, Ito R, Hiraoka N, McManus MT, Kanai Y, Hebrok M. Disruption of Dicer1 induces dysregulated fetal gene expression and promotes hepatocarcinogenesis. Gastroenterology. 2009 Jun; 136(7):2304-2315.e1-4. PMID: 19272382; PMCID: PMC3167383.
    64. Nolan-Stevaux O, Lau J, Truitt ML, Chu GC, Hebrok M, Fernández-Zapico ME, Hanahan D. GLI1 is regulated through Smoothened-independent mechanisms in neoplastic pancreatic ducts and mediates PDAC cell survival and transformation. Genes Dev. 2009 Jan 1; 23(1):24-36. PMID: 19136624; PMCID: PMC2632164.
    65. Cervantes S, Yamaguchi TP, Hebrok M. Wnt5a is essential for intestinal elongation in mice. Dev Biol. 2009 Feb 15; 326(2):285-94. PMID: 19100728; PMCID: PMC2654720.
    66. Puri S, Cano DA, Hebrok M. A role for von Hippel-Lindau protein in pancreatic beta-cell function. Diabetes. 2009 Feb; 58(2):433-41. PMID: 19033400; PMCID: PMC2628617.
    67. Cano DA, Hebrok M. Hedgehog spikes pancreas regeneration. Gastroenterology. 2008 Aug; 135(2):347-51. PMID: 18619970.
      View in: PubMed
    68. Heiser PW, Cano DA, Landsman L, Kim GE, Kench JG, Klimstra DS, Taketo MM, Biankin AV, Hebrok M. Stabilization of beta-catenin induces pancreas tumor formation. Gastroenterology. 2008 Oct; 135(4):1288-300. PMID: 18725219; PMCID: PMC2613004.
    69. Bluestone JA, Hebrok M. Safer, longer-lasting regulatory T cells with beta-catenin. Nat Med. 2008 Feb; 14(2):118-9. PMID: 18256611.
      View in: PubMed
    70. Cano DA, Rulifson IC, Heiser PW, Swigart LB, Pelengaris S, German M, Evan GI, Bluestone JA, Hebrok M. Regulated beta-cell regeneration in the adult mouse pancreas. Diabetes. 2008 Apr; 57(4):958-66. PMID: 18083786.
      View in: PubMed
    71. Regard JB, Kataoka H, Cano DA, Camerer E, Yin L, Zheng YW, Scanlan TS, Hebrok M, Coughlin SR. Probing cell type-specific functions of Gi in vivo identifies GPCR regulators of insulin secretion. J Clin Invest. 2007 Dec; 117(12):4034-43. PMID: 17992256; PMCID: PMC2066199.
    72. Pasca di Magliano M, Biankin AV, Heiser PW, Cano DA, Gutierrez PJ, Deramaudt T, Segara D, Dawson AC, Kench JG, Henshall SM, Sutherland RL, Dlugosz A, Rustgi AK, Hebrok M. Common activation of canonical Wnt signaling in pancreatic adenocarcinoma. PLoS One. 2007; 2(11):e1155. PMID: 17982507; PMCID: PMC2048934.
    73. Burris RE, Hebrok M. Pancreatic innervation in mouse development and beta-cell regeneration. Neuroscience. 2007 Dec 12; 150(3):592-602. PMID: 18006238; PMCID: PMC2245866.
    74. Nawroth R, van Zante A, Cervantes S, McManus M, Hebrok M, Rosen SD. Extracellular sulfatases, elements of the Wnt signaling pathway, positively regulate growth and tumorigenicity of human pancreatic cancer cells. PLoS One. 2007; 2(4):e392. PMID: 17460759; PMCID: PMC1849966.
    75. Robbins DJ, Hebrok M. Hedgehogs: la dolce vita. Workshop on Hedgehog-Gli Signaling in Cancer and Stem Cells. EMBO Rep. 2007 May; 8(5):451-5. PMID: 17431408; PMCID: PMC1866211.
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    77. Morton JP, Mongeau ME, Klimstra DS, Morris JP, Lee YC, Kawaguchi Y, Wright CV, Hebrok M, Lewis BC. Sonic hedgehog acts at multiple stages during pancreatic tumorigenesis. Proc Natl Acad Sci U S A. 2007 Mar 20; 104(12):5103-8. PMID: 17372229; PMCID: PMC1828712.
    78. Puri S, Hebrok M. Dynamics of embryonic pancreas development using real-time imaging. Dev Biol. 2007 Jun 1; 306(1):82-93. PMID: 17448459; PMCID: PMC1988845.
    79. Cano DA, Hebrok M, Zenker M. Pancreatic development and disease. Gastroenterology. 2007 Feb; 132(2):745-62. PMID: 17258745.
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    80. Sekine S, Gutiérrez PJ, Lan BY, Feng S, Hebrok M. Liver-specific loss of beta-catenin results in delayed hepatocyte proliferation after partial hepatectomy. Hepatology. 2007 Feb; 45(2):361-8. PMID: 17256747.
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    81. Pasca di Magliano M, Sekine S, Ermilov A, Ferris J, Dlugosz AA, Hebrok M. Hedgehog/Ras interactions regulate early stages of pancreatic cancer. Genes Dev. 2006 Nov 15; 20(22):3161-73. PMID: 17114586; PMCID: PMC1635150.
    82. Cano DA, Sekine S, Hebrok M. Primary cilia deletion in pancreatic epithelial cells results in cyst formation and pancreatitis. Gastroenterology. 2006 Dec; 131(6):1856-69. PMID: 17123526.
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    83. Heiser PW, Lau J, Taketo MM, Herrera PL, Hebrok M. Stabilization of beta-catenin impacts pancreas growth. Development. 2006 May; 133(10):2023-32. PMID: 16611688.
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    84. Sekine S, Lan BY, Bedolli M, Feng S, Hebrok M. Liver-specific loss of beta-catenin blocks glutamine synthesis pathway activity and cytochrome p450 expression in mice. Hepatology. 2006 Apr; 43(4):817-25. PMID: 16557553.
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    85. Lau J, Kawahira H, Hebrok M. Hedgehog signaling in pancreas development and disease. Cell Mol Life Sci. 2006 Mar; 63(6):642-52. PMID: 16465449.
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    86. Kawahira H, Scheel DW, Smith SB, German MS, Hebrok M. Hedgehog signaling regulates expansion of pancreatic epithelial cells. Dev Biol. 2005 Apr 1; 280(1):111-21. PMID: 15766752.
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    87. Perez SE, Cano DA, Dao-Pick T, Rougier JP, Werb Z, Hebrok M. Matrix metalloproteinases 2 and 9 are dispensable for pancreatic islet formation and function in vivo. Diabetes. 2005 Mar; 54(3):694-701. PMID: 15734845; PMCID: PMC2771170.
    88. Cano DA, Murcia NS, Pazour GJ, Hebrok M. Orpk mouse model of polycystic kidney disease reveals essential role of primary cilia in pancreatic tissue organization. Development. 2004 Jul; 131(14):3457-67. PMID: 15226261.
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    89. Hebrok M, Reichardt LF. Brain meets pancreas: netrin, an axon guidance molecule, controls epithelial cell migration. Trends Cell Biol. 2004 Apr; 14(4):153-5. PMID: 15134068; PMCID: PMC2744962.
    90. Heiser PW, Hebrok M. Development and cancer: lessons learned in the pancreas. Cell Cycle. 2004 Mar; 3(3):270-2. PMID: 14726662.
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    91. Pasca di Magliano M, Hebrok M. Hedgehog signalling in cancer formation and maintenance. Nat Rev Cancer. 2003 Dec; 3(12):903-11. PMID: 14737121.
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    92. Thayer SP, di Magliano MP, Heiser PW, Nielsen CM, Roberts DJ, Lauwers GY, Qi YP, Gysin S, Fernández-del Castillo C, Yajnik V, Antoniu B, McMahon M, Warshaw AL, Hebrok M. Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature. 2003 Oct 23; 425(6960):851-6. PMID: 14520413; PMCID: PMC3688051.
    93. Kawahira H, Ma NH, Tzanakakis ES, McMahon AP, Chuang PT, Hebrok M. Combined activities of hedgehog signaling inhibitors regulate pancreas development. Development. 2003 Oct; 130(20):4871-9. PMID: 12917290.
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    94. Hebrok M. Hedgehog signaling in pancreas development. Mech Dev. 2003 Jan; 120(1):45-57. PMID: 12490295.
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    95. Kim SK, Hebrok M. Intercellular signals regulating pancreas development and function. Genes Dev. 2001 Jan 15; 15(2):111-27. PMID: 11157769.
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    96. Hebrok M, Kim SK, St Jacques B, McMahon AP, Melton DA. Regulation of pancreas development by hedgehog signaling. Development. 2000 Nov; 127(22):4905-13. PMID: 11044404.
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    97. Kim SK, Hebrok M, Li E, Oh SP, Schrewe H, Harmon EB, Lee JS, Melton DA. Activin receptor patterning of foregut organogenesis. Genes Dev. 2000 Aug 1; 14(15):1866-71. PMID: 10921901; PMCID: PMC316826.
    98. Hebrok M, Kim SK, Melton DA. Screening for novel pancreatic genes expressed during embryogenesis. Diabetes. 1999 Aug; 48(8):1550-6. PMID: 10426372.
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    99. Hebrok M, Kim SK, Melton DA. Notochord repression of endodermal Sonic hedgehog permits pancreas development. Genes Dev. 1998 Jun 1; 12(11):1705-13. PMID: 9620856; PMCID: PMC316875.
    100. Kim SK, Hebrok M, Melton DA. Notochord to endoderm signaling is required for pancreas development. Development. 1997 Nov; 124(21):4243-52. PMID: 9334273.
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    101. Hebrok M, Füchtbauer A, Füchtbauer EM. Repression of muscle-specific gene activation by the murine Twist protein. Exp Cell Res. 1997 May 1; 232(2):295-303. PMID: 9168805.
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    102. Kim SK, Hebrok M, Melton DA. Pancreas development in the chick embryo. Cold Spring Harb Symp Quant Biol. 1997; 62:377-83. PMID: 9598372.
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    103. Rohwedel J, Horák V, Hebrok M, Füchtbauer EM, Wobus AM. M-twist expression inhibits mouse embryonic stem cell-derived myogenic differentiation in vitro. Exp Cell Res. 1995 Sep; 220(1):92-100. PMID: 7664846.
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    104. Hebrok M, Wertz K, Füchtbauer EM. M-twist is an inhibitor of muscle differentiation. Dev Biol. 1994 Oct; 165(2):537-44. PMID: 7958419.
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