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Matthias Hebrok, PhD

Title(s)Professor, Diabetes Center
SchoolSchool of Medicine
Address513 Parnassus Ave, HSW
San Francisco CA 94143
Phone415-514-0820
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    Other Positions
    Title(s)Director, 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
    Modeling autoimmune pathogenesis and beta cell destruction by T1D immune systems
    NIH/NIDDK U01DK123559Sep 20, 2019 - May 31, 2023
    Role: Co-Principal Investigator
    Microphysiological systems to interrogate the Islet-Liver-Adipose Axis in normal physiology and Type-2 Diabetes Mellitus
    NIH/NIDDK UH3DK120004Sep 20, 2018 - Jul 31, 2023
    Role: Co-Principal Investigator
    Microphysiological systems to interrogate the Islet-Liver-Adipose Axis in normal physiology and Type-2 Diabetes Mellitus
    NIH/NIDDK UG3DK120004Sep 20, 2018 - Jul 31, 2020
    Role: Co-Principal Investigator
    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 - Jul 31, 2023
    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 P30DK063720May 1, 2003 - Mar 31, 2020
    Role: Co-Investigator
    Effects of Hedgehog Signaling on Pancreas Organogenesis
    NIH/NIDDK R01DK060533Dec 1, 2001 - Mar 31, 2010
    Role: Principal Investigator
    Molecular Control of Pancreatic Islet Development
    NIH/NIDDK U19DK061245Sep 30, 2001 - Sep 29, 2005
    Role: Co-Investigator

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    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. to make corrections and additions.
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    Altmetrics Details PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Emerging routes to the generation of functional ß-cells for diabetes mellitus cell therapy. Nat Rev Endocrinol. 2020 Jun 25. Nair GG, Tzanakakis ES, Hebrok M. PMID: 32587391.
      View in: PubMed   Mentions:    Fields:    
    2. Loss of the transcription factor MAFB limits ß-cell derivation from human PSCs. Nat Commun. 2020 Jun 02; 11(1):2742. Russell R, Carnese PP, Hennings TG, Walker EM, Russ HA, Liu JS, Giacometti S, Stein R, Hebrok M. PMID: 32488111.
      View in: PubMed   Mentions:    Fields:    
    3. LIN28B Impairs the Transition of hESC-Derived ß Cells from the Juvenile to Adult State. Stem Cell Reports. 2020 01 14; 14(1):9-20. Zhou X, Nair GG, Russ HA, Belair CD, Li ML, Shveygert M, Hebrok M, Blelloch R. PMID: 31883920.
      View in: PubMed   Mentions:    Fields:    
    4. Lipid Droplet Accumulation in Human Pancreatic Islets Is Dependent On Both Donor Age and Health. Diabetes. 2020 Mar; 69(3):342-354. Tong X, Dai C, Walker JT, Nair GG, Kennedy A, Carr RM, Hebrok M, Powers AC, Stein R. PMID: 31836690.
      View in: PubMed   Mentions: 1     Fields:    
    5. Using a barcoded AAV capsid library to select for clinically relevant gene therapy vectors. JCI Insight. 2019 11 14; 4(22). Pekrun K, De Alencastro G, Luo QJ, Liu J, Kim Y, Nygaard S, Galivo F, Zhang F, Song R, Tiffany MR, Xu J, Hebrok M, Grompe M, Kay MA. PMID: 31723052.
      View in: PubMed   Mentions: 4     Fields:    
    6. Supporting Survival of Transplanted Stem-Cell-Derived Insulin-Producing Cells in an Encapsulation Device Augmented with Controlled Release of Amino Acids. Adv Biosyst. 2019 Sep; 3(9). Chendke GS, Faleo G, Juang C, Parent AV, Bernards DA, Hebrok M, Tang Q, Desai TA. PMID: 31633004.
      View in: PubMed   Mentions:
    7. mTORC1 to AMPK switching underlies ß-cell metabolic plasticity during maturation and diabetes. J Clin Invest. 2019 07 02; 129(10):4124-4137. Jaafar R, Tran S, Shah AN, Sun G, Valdearcos M, Marchetti P, Masini M, Swisa A, Giacometti S, Bernal-Mizrachi E, Matveyenko A, Hebrok M, Dor Y, Rutter GA, Koliwad SK, Bhushan A. PMID: 31265435.
      View in: PubMed   Mentions:    Fields:    Translation:AnimalsCells
    8. The Pdx1-Bound Swi/Snf Chromatin Remodeling Complex Regulates Pancreatic Progenitor Cell Proliferation and Mature Islet ß-Cell Function. Diabetes. 2019 09; 68(9):1806-1818. Spaeth JM, Liu JH, Peters D, Guo M, Osipovich AB, Mohammadi F, Roy N, Bhushan A, Magnuson MA, Hebrok M, Wright CVE, Stein R. PMID: 31201281.
      View in: PubMed   Mentions: 1     Fields:    Translation:AnimalsCells
    9. Author Correction: Recapitulating endocrine cell clustering in culture promotes maturation of human stem-cell-derived ß cells. Nat Cell Biol. 2019 06; 21(6):792. Nair GG, Liu JS, Russ HA, Tran S, Saxton MS, Chen R, Juang C, Li ML, Nguyen VQ, Giacometti S, Puri S, Xing Y, Wang Y, Szot GL, Oberholzer J, Bhushan A, Hebrok M. PMID: 30914825.
      View in: PubMed   Mentions:    Fields:    
    10. Pancreatic pericytes originate from the embryonic pancreatic mesenchyme. Dev Biol. 2019 05 01; 449(1):14-20. Harari N, Sakhneny L, Khalifa-Malka L, Busch A, Hertel KJ, Hebrok M, Landsman L. PMID: 30771302.
      View in: PubMed   Mentions:    Fields:    Translation:AnimalsCells
    11. Rapid generation of functional mature pancreatic islet-beta cells from human pluripotent stem cells. Protocol Exchange. 2019 Feb 4. Gopika Nair, Gopika Nair, Holger Russ, Matthias Hebrok. .
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    12. Recapitulating endocrine cell clustering in culture promotes maturation of human stem-cell-derived ß cells. Nat Cell Biol. 2019 02; 21(2):263-274. Nair GG, Liu JS, Russ HA, Tran S, Saxton MS, Chen R, Juang C, Li ML, Nguyen VQ, Giacometti S, Puri S, Xing Y, Wang Y, Szot GL, Oberholzer J, Bhushan A, Hebrok M. PMID: 30710150.
      View in: PubMed   Mentions: 15     Fields:    Translation:HumansAnimalsCells
    13. The BRG1/SOX9 axis is critical for acinar cell-derived pancreatic tumorigenesis. J Clin Invest. 2018 08 01; 128(8):3475-3489. Tsuda M, Fukuda A, Roy N, Hiramatsu Y, Leonhardt L, Kakiuchi N, Hoyer K, Ogawa S, Goto N, Ikuta K, Kimura Y, Matsumoto Y, Takada Y, Yoshioka T, Maruno T, Yamaga Y, Kim GE, Akiyama H, Ogawa S, Wright CV, Saur D, Takaori K, Uemoto S, Hebrok M, Chiba T, Seno H. PMID: 30010625.
      View in: PubMed   Mentions: 4     Fields:    Translation:HumansAnimalsCells
    14. Co-Transplant of Parathyroid Gland and Stem Cell-Derived Insulin-Producing Cells Enhances Graft Survival through Release of Pro-Angiogenic and Pro-Survival Factors. Transplantation Journal. 2018 Jul 1; 102(&NA;):s350. Gaetano Faleo, Casey Ward, Audrey Parent, Gopika Nair, Wenhan Chang, Peter Stock, Matthias Hebrok, Qizhi Tang. .
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    15. Stem Cell Therapies for Treating Diabetes: Progress and Remaining Challenges. Cell Stem Cell. 2018 Jun 01; 22(6):810-823. Sneddon JB, Tang Q, Stock P, Bluestone JA, Roy S, Desai T, Hebrok M. PMID: 29859172.
      View in: PubMed   Mentions: 9     Fields:    Translation:HumansAnimalsCells
    16. Synaptotagmin 4 Regulates Pancreatic ß Cell Maturation by Modulating the Ca2+ Sensitivity of Insulin Secretion Vesicles. Dev Cell. 2018 05 07; 45(3):347-361.e5. Huang C, Walker EM, Dadi PK, Hu R, Xu Y, Zhang W, Sanavia T, Mun J, Liu J, Nair GG, Tan HYA, Wang S, Magnuson MA, Stoeckert CJ, Hebrok M, Gannon M, Han W, Stein R, Jacobson DA, Gu G. PMID: 29656931.
      View in: PubMed   Mentions: 4     Fields:    Translation:HumansAnimalsCells
    17. Replication confers ß cell immaturity. Nat Commun. 2018 02 02; 9(1):485. Puri S, Roy N, Russ HA, Leonhardt L, French EK, Roy R, Bengtsson H, Scott DK, Stewart AF, Hebrok M. PMID: 29396395.
      View in: PubMed   Mentions: 6     Fields:    Translation:AnimalsCells
    18. Mitigating Ischemic Injury of Stem Cell-Derived Insulin-Producing Cells after Transplant. Stem Cell Reports. 2017 09 12; 9(3):807-819. Faleo G, Russ HA, Wisel S, Parent AV, Nguyen V, Nair GG, Freise JE, Villanueva KE, Szot GL, Hebrok M, Tang Q. PMID: 28803916.
      View in: PubMed   Mentions: 1     Fields:    Translation:HumansAnimalsCells
    19. Nanoporous Immunoprotective Device for Stem-Cell-Derived ß-Cell Replacement Therapy. ACS Nano. 2017 08 22; 11(8):7747-7757. Chang R, Faleo G, Russ HA, Parent AV, Elledge SK, Bernards DA, Allen JL, Villanueva K, Hebrok M, Tang Q, Desai TA. PMID: 28763191.
      View in: PubMed   Mentions: 3     Fields:    Translation:Animals
    20. Corticotropin-releasing hormone type 2 receptor deficiency impairs pancreatic function in a sex-specific manner. Pancreatology. 2017 Jul 1; 17(3):s8. Aditi Bhargava, Shinichiro Hagiwara, Sapna Puri, Matthias Hebrok, Gregory Szot, Burcu Hasdemir, Sreenivasan Paruthiyil. .
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    21. Atypical flat lesions derive from pancreatic acinar cells. Pancreatology. 2017 May - Jun; 17(3):350-353. von Figura G, Fahrenkrog-Petersen L, Hidalgo-Sastre A, Hartmann D, Hüser N, Schmid RM, Hebrok M, Roy N, Esposito I. PMID: 28473229.
      View in: PubMed   Mentions:    Fields:    Translation:AnimalsCells
    22. Global Protease Activity Profiling Provides Differential Diagnosis of Pancreatic Cysts. Clin Cancer Res. 2017 Aug 15; 23(16):4865-4874. Ivry SL, Sharib JM, Dominguez DA, Roy N, Hatcher SE, Yip-Schneider MT, Schmidt CM, Brand RE, Park WG, Hebrok M, Kim GE, O'Donoghue AJ, Kirkwood KS, Craik CS. PMID: 28424202.
      View in: PubMed   Mentions: 4     Fields:    Translation:HumansAnimals
    23. Designing ß Cells. Cell Metab. 2017 02 07; 25(2):223-224. Hebrok M. PMID: 28178560.
      View in: PubMed   Mentions:    Fields:    Translation:HumansAnimalsCells
    24. All mixed up: defining roles for ß-cell subtypes in mature islets. Genes Dev. 2017 02 01; 31(3):228-240. Liu JS, Hebrok M. PMID: 28270515.
      View in: PubMed   Mentions: 9     Fields:    Translation:HumansAnimalsCells
    25. PDX1 dynamically regulates pancreatic ductal adenocarcinoma initiation and maintenance. Genes Dev. 2016 12 15; 30(24):2669-2683. 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. PMID: 28087712.
      View in: PubMed   Mentions: 11     Fields:    Translation:HumansAnimalsCells
    26. Rebranding asymptomatic type 1 diabetes: the case for autoimmune beta cell disorder as a pathological and diagnostic entity. Diabetologia. 2017 01; 60(1):35-38. 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. PMID: 27785529.
      View in: PubMed   Mentions: 5     Fields:    Translation:HumansCells
    27. Loss of Pancreas upon Activated Wnt Signaling Is Concomitant with Emergence of Gastrointestinal Identity. PLoS One. 2016; 11(10):e0164714. Muñoz-Bravo JL, Flores-Martínez A, Herrero-Martin G, Puri S, Taketo MM, Rojas A, Hebrok M, Cano DA. PMID: 27736991.
      View in: PubMed   Mentions: 2     Fields:    Translation:AnimalsCells
    28. Human islets contain four distinct subtypes of ß cells. Nat Commun. 2016 07 11; 7:11756. Dorrell C, Schug J, Canaday PS, Russ HA, Tarlow BD, Grompe MT, Horton T, Hebrok M, Streeter PR, Kaestner KH, Grompe M. PMID: 27399229.
      View in: PubMed   Mentions: 72     Fields:    Translation:HumansCells
    29. Genotype tunes pancreatic ductal adenocarcinoma tissue tension to induce matricellular fibrosis and tumor progression. Nat Med. 2016 05; 22(5):497-505. 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. PMID: 27089513.
      View in: PubMed   Mentions: 95     Fields:    Translation:HumansAnimalsCells
    30. p120 Catenin Suppresses Basal Epithelial Cell Extrusion in Invasive Pancreatic Neoplasia. Cancer Res. 2016 06 01; 76(11):3351-63. 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 AB, Goggins M, Younes M, Iacobuzio-Donahue CA, Leach SD, Bailey JM. PMID: 27032419.
      View in: PubMed   Mentions: 6     Fields:    Translation:HumansAnimalsCells
    31. Life and death of ß cells in Type 1 diabetes: A comprehensive review. J Autoimmun. 2016 07; 71:51-8. Wilcox NS, Rui J, Hebrok M, Herold KC. PMID: 27017348.
      View in: PubMed   Mentions: 9     Fields:    Translation:HumansAnimalsCells
    32. A functional circadian clock is required for proper insulin secretion by human pancreatic islet cells. Diabetes Obes Metab. 2016 Apr; 18(4):355-65. Saini C, Petrenko V, Pulimeno P, Giovannoni L, Berney T, Hebrok M, Howald C, Dermitzakis ET, Dibner C. PMID: 26662378.
      View in: PubMed   Mentions: 20     Fields:    Translation:HumansCells
    33. Human pancreatic beta-like cells converted from fibroblasts. Nat Commun. 2016 Jan 06; 7:10080. Zhu S, Russ HA, Wang X, Zhang M, Ma T, Xu T, Tang S, Hebrok M, Ding S. PMID: 26733021.
      View in: PubMed   Mentions: 21     Fields:    Translation:HumansAnimalsCells
    34. Chapter 30 Development of the Endocrine Pancreas. Endocrinology: Adult and Pediatric. 2016 Jan 1; 517-526.e5. Matthias Hebrok, Michael S. German. .
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    35. Regulation of Cellular Identity in Cancer. Dev Cell. 2015 Dec 21; 35(6):674-84. Roy N, Hebrok M. PMID: 26702828.
      View in: PubMed   Mentions: 21     Fields:    Translation:HumansAnimalsCells
    36. ß-Cell Insulin Secretion Requires the Ubiquitin Ligase COP1. Cell. 2015 Dec 03; 163(6):1457-67. 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. PMID: 26627735.
      View in: PubMed   Mentions: 10     Fields:    Translation:HumansAnimalsCells
    37. 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. Russ HA, Landsman L, Moss CL, Higdon R, Greer RL, Kaihara K, Salamon R, Kolker E, Hebrok M. PMID: 26681951.
      View in: PubMed   Mentions:
    38. Human stem cells from single blastomeres reveal pathways of embryonic or trophoblast fate specification. Development. 2015 Dec 01; 142(23):4010-25. 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. PMID: 26483210.
      View in: PubMed   Mentions: 16     Fields:    Translation:HumansCells
    39. DNA methylation directs functional maturation of pancreatic ß cells. J Clin Invest. 2015 Jul 01; 125(7):2851-60. Dhawan S, Tschen SI, Zeng C, Guo T, Hebrok M, Matveyenko A, Bhushan A. PMID: 26098213.
      View in: PubMed   Mentions: 34     Fields:    Translation:HumansAnimalsCells
    40. Controlled induction of human pancreatic progenitors produces functional beta-like cells in vitro. EMBO J. 2015 Jul 02; 34(13):1759-72. 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. PMID: 25908839.
      View in: PubMed   Mentions: 101     Fields:    Translation:HumansAnimalsCells
    41. 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. Nair G, Hebrok M. PMID: 25909383.
      View in: PubMed   Mentions: 19     Fields:    Translation:HumansAnimalsCells
    42. Brg1 promotes both tumor-suppressive and oncogenic activities at distinct stages of pancreatic cancer formation. Genes Dev. 2015 Mar 15; 29(6):658-71. Roy N, Malik S, Villanueva KE, Urano A, Lu X, Von Figura G, Seeley ES, Dawson DW, Collisson EA, Hebrok M. PMID: 25792600.
      View in: PubMed   Mentions: 36     Fields:    Translation:HumansAnimalsCells
    43. 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. Huskey NE, Guo T, Evason KJ, Momcilovic O, Pardo D, Creasman KJ, Judson RL, Blelloch R, Oakes SA, Hebrok M, Goga A. PMID: 25733019.
      View in: PubMed   Mentions: 27     Fields:    Translation:HumansAnimalsCells
    44. NFATc1 Links EGFR Signaling to Induction of Sox9 Transcription and Acinar-Ductal Transdifferentiation in the Pancreas. Gastroenterology. 2015 May; 148(5):1024-1034.e9. 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. PMID: 25623042.
      View in: PubMed   Mentions: 18     Fields:    Translation:HumansAnimalsCells
    45. Antithetical NFATc1-Sox2 and p53-miR200 signaling networks govern pancreatic cancer cell plasticity. EMBO J. 2015 Feb 12; 34(4):517-30. 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. PMID: 25586376.
      View in: PubMed   Mentions: 19     Fields:    Translation:HumansAnimalsCells
    46. Plasticity and dedifferentiation within the pancreas: development, homeostasis, and disease. Cell Stem Cell. 2015 Jan 08; 16(1):18-31. Puri S, Folias AE, Hebrok M. PMID: 25465113.
      View in: PubMed   Mentions: 41     Fields:    Translation:Humans
    47. Taming the young and restless--epigenetic gene regulation in pancreas and beta-cell precursors. EMBO J. 2014 Oct 01; 33(19):2135-6. Russ HA, Hebrok M. PMID: 25154606.
      View in: PubMed   Mentions: 2     Fields:    Translation:HumansAnimalsCells
    48. Aberrant innate immune activation following tissue injury impairs pancreatic regeneration. PLoS One. 2014; 9(7):e102125. Folias AE, Penaranda C, Su AL, Bluestone JA, Hebrok M. PMID: 25010227.
      View in: PubMed   Mentions: 14     Fields:    Translation:AnimalsCells
    49. Dicer regulates differentiation and viability during mouse pancreatic cancer initiation. PLoS One. 2014; 9(5):e95486. Morris JP, Greer R, Russ HA, von Figura G, Kim GE, Busch A, Lee J, Hertel KJ, Kim S, McManus M, Hebrok M. PMID: 24788257.
      View in: PubMed   Mentions: 9     Fields:    Translation:AnimalsCells
    50. Generation of insulin-producing cells from human stem cells (207.3). The FASEB Journal. 2014 Apr 1; 28. Matthias Hebrok. .
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    51. Analyzing pancreas development with the goal to generate functional ß-cells from stem cells and prevent neoplastic transformation. Pancreatology. 2014 Mar 1; 14(2):e5. Matthias Hebrok. .
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    52. Diabetes. Solving human ß-cell development--what does the mouse say? Nat Rev Endocrinol. 2014 May; 10(5):253-5. Folias AE, Hebrok M. PMID: 24566816.
      View in: PubMed   Mentions:    Fields:    Translation:HumansAnimals
    53. The chromatin regulator Brg1 suppresses formation of intraductal papillary mucinous neoplasm and pancreatic ductal adenocarcinoma. Nat Cell Biol. 2014 Mar; 16(3):255-67. 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. PMID: 24561622.
      View in: PubMed   Mentions: 52     Fields:    Translation:HumansAnimalsCells
    54. Small molecules facilitate the reprogramming of mouse fibroblasts into pancreatic lineages. Cell Stem Cell. 2014 Feb 06; 14(2):228-36. Li K, Zhu S, Russ HA, Xu S, Xu T, Zhang Y, Ma T, Hebrok M, Ding S. PMID: 24506886.
      View in: PubMed   Mentions: 37     Fields:    Translation:AnimalsCells
    55. Overview. Metabolism of Human Diseases. 2014 Jan 1; 157-162. Alexandra E. Folias, Matthias Hebrok. .
      View in: Publisher Site   Mentions:
    56. VHL-mediated disruption of Sox9 activity compromises ß-cell identity and results in diabetes mellitus. Genes Dev. 2013 Dec 01; 27(23):2563-75. Puri S, Akiyama H, Hebrok M. PMID: 24298056.
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    57. Elimination of von Hippel-Lindau function perturbs pancreas endocrine homeostasis in mice. PLoS One. 2013; 8(8):e72213. Puri S, García-Núñez A, Hebrok M, Cano DA. PMID: 23977255.
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    58. Numb regulates acinar cell dedifferentiation and survival during pancreatic damage and acinar-to-ductal metaplasia. Gastroenterology. 2013 Nov; 145(5):1088-1097.e8. Greer RL, Staley BK, Liou A, Hebrok M. PMID: 23891977.
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    59. Canonical wnt signaling is required for pancreatic carcinogenesis. Cancer Res. 2013 Aug 01; 73(15):4909-22. Zhang Y, Morris JP, Yan W, Schofield HK, Gurney A, Simeone DM, Millar SE, Hoey T, Hebrok M, Pasca di Magliano M. PMID: 23761328.
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    60. Control of cell identity in pancreas development and regeneration. Gastroenterology. 2013 Jun; 144(6):1170-9. Stanger BZ, Hebrok M. PMID: 23622126.
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    61. Generation of functional thymic epithelium from human embryonic stem cells that supports host T cell development. Cell Stem Cell. 2013 Aug 01; 13(2):219-29. Parent AV, Russ HA, Khan IS, LaFlam TN, Metzger TC, Anderson MS, Hebrok M. PMID: 23684540.
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    62. Nr5a2 maintains acinar cell differentiation and constrains oncogenic Kras-mediated pancreatic neoplastic initiation. Gut. 2014 Apr; 63(4):656-64. von Figura G, Morris JP, Wright CV, Hebrok M. PMID: 23645620.
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    63. Dormant cancer cells contribute to residual disease in a model of reversible pancreatic cancer. Cancer Res. 2013 Mar 15; 73(6):1821-30. 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. PMID: 23467612.
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    64. Factors expressed by murine embryonic pancreatic mesenchyme enhance generation of insulin-producing cells from hESCs. Diabetes. 2013 May; 62(5):1581-92. Guo T, Landsman L, Li N, Hebrok M. PMID: 23305648.
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    65. 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. 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. PMID: 23201164.
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    66. Advances in acute and chronic pancreatitis: from development to inflammation and repair. Gastroenterology. 2013 Jan; 144(1):e1-4. Pasca di Magliano M, Forsmark C, Freedman S, Hebrok M, Pasricha PJ, Saluja A, Stanger BZ, Holt J, Serrano J, James SP, Rustgi AK. PMID: 23159450.
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    67. Diabetic ß Cells: To Be or Not To Be? Cell. 2012 Sep 14; 150(6):1103-4. Puri S, Hebrok M. PMID: 22980973.
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    68. Generating ß cells from stem cells-the story so far. Cold Spring Harb Perspect Med. 2012 Jun; 2(6):a007674. Hebrok M. PMID: 22675664.
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    69. Bmi1 is required for regeneration of the exocrine pancreas in mice. Gastroenterology. 2012 Sep; 143(3):821-831.e2. Fukuda A, Morris JP, Hebrok M. PMID: 22609312.
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    70. Transcriptional analysis of pluripotency reveals the Hippo pathway as a barrier to reprogramming. Hum Mol Genet. 2012 May 01; 21(9):2054-67. Qin H, Blaschke K, Wei G, Ohi Y, Blouin L, Qi Z, Yu J, Yeh RF, Hebrok M, Ramalho-Santos M. PMID: 22286172.
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    71. Elevated Hedgehog/Gli signaling causes beta-cell dedifferentiation in mice. Proc Natl Acad Sci U S A. 2011 Oct 11; 108(41):17010-5. Landsman L, Parent A, Hebrok M. PMID: 21969560.
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    72. Pancreatic mesenchyme regulates epithelial organogenesis throughout development. PLoS Biol. 2011 Sep; 9(9):e1001143. Landsman L, Nijagal A, Whitchurch TJ, Vanderlaan RL, Zimmer WE, Mackenzie TC, Hebrok M. PMID: 21909240.
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    73. How does type 1 diabetes develop?: the notion of homicide or ß-cell suicide revisited. Diabetes. 2011 May; 60(5):1370-9. Atkinson MA, Bluestone JA, Eisenbarth GS, Hebrok M, Herold KC, Accili D, Pietropaolo M, Arvan PR, Von Herrath M, Markel DS, Rhodes CJ. PMID: 21525508.
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    74. Incomplete DNA methylation underlies a transcriptional memory of somatic cells in human iPS cells. Nat Cell Biol. 2011 May; 13(5):541-9. 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. PMID: 21499256.
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    75. Stat3 and MMP7 contribute to pancreatic ductal adenocarcinoma initiation and progression. Cancer Cell. 2011 Apr 12; 19(4):441-55. Fukuda A, Wang SC, Morris JP, Folias AE, Liou A, Kim GE, Akira S, Boucher KM, Firpo MA, Mulvihill SJ, Hebrok M. PMID: 21481787.
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    76. KRAS, Hedgehog, Wnt and the twisted developmental biology of pancreatic ductal adenocarcinoma. Nat Rev Cancer. 2010 Oct; 10(10):683-95. Morris JP, Wang SC, Hebrok M. PMID: 20814421.
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    77. Stat3 and MMP7 mediate multiple aspects of pancreatic ductal adenocarcinoma biology. Journal of the American College of Surgeons. 2010 Sep 1; 211(3):s120. Sam C. Wang, Akihisa Fukuda, John P. Morris, Angela Liou, Shizuo Akira, Matthias Hebrok. .
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    78. Dynamic switch of negative feedback regulation in Drosophila Akt-TOR signaling. PLoS Genet. 2010 Jun 17; 6(6):e1000990. Kockel L, Kerr KS, Melnick M, Brückner K, Hebrok M, Perrimon N. PMID: 20585550.
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    79. Primary cilia regulate Gli/Hedgehog activation in pancreas. Proc Natl Acad Sci U S A. 2010 Jun 01; 107(22):10109-14. Cervantes S, Lau J, Cano DA, Borromeo-Austin C, Hebrok M. PMID: 20479231.
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    80. Cellular plasticity within the pancreas--lessons learned from development. Dev Cell. 2010 Mar 16; 18(3):342-56. Puri S, Hebrok M. PMID: 20230744.
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    81. Hedgehog signaling in pancreas epithelium regulates embryonic organ formation and adult beta-cell function. Diabetes. 2010 May; 59(5):1211-21. Lau J, Hebrok M. PMID: 20185815.
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    82. Beta-catenin blocks Kras-dependent reprogramming of acini into pancreatic cancer precursor lesions in mice. J Clin Invest. 2010 Feb; 120(2):508-20. Morris JP, Cano DA, Sekine S, Wang SC, Hebrok M. PMID: 20071774.
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    83. Hedgehog Signaling Pathways in Pancreatic Cancer Pathogenesis. Pancreatic Cancer. 2010 Jan 1; 403-418. Marina Pasca di Magliano, Matthias Hebrok. .
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    84. It's a free for all--insulin-positive cells join the group of potential progenitors for pancreatic ductal adenocarcinoma. Cancer Cell. 2009 Nov 06; 16(5):359-61. Morris JP, Hebrok M. PMID: 19878864.
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    85. Dicer is required for proper liver zonation. J Pathol. 2009 Nov; 219(3):365-72. Sekine S, Ogawa R, Mcmanus MT, Kanai Y, Hebrok M. PMID: 19718708.
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    86. Stem cells to pancreatic beta-cells: new sources for diabetes cell therapy. Endocr Rev. 2009 May; 30(3):214-27. Guo T, Hebrok M. PMID: 19389995.
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    87. Disruption of Dicer1 induces dysregulated fetal gene expression and promotes hepatocarcinogenesis. Gastroenterology. 2009 Jun; 136(7):2304-2315.e1-4. Sekine S, Ogawa R, Ito R, Hiraoka N, McManus MT, Kanai Y, Hebrok M. PMID: 19272382.
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    88. GLI1 is regulated through Smoothened-independent mechanisms in neoplastic pancreatic ducts and mediates PDAC cell survival and transformation. Genes Dev. 2009 Jan 01; 23(1):24-36. Nolan-Stevaux O, Lau J, Truitt ML, Chu GC, Hebrok M, Fernández-Zapico ME, Hanahan D. PMID: 19136624.
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    89. Wnt5a is essential for intestinal elongation in mice. Dev Biol. 2009 Feb 15; 326(2):285-94. Cervantes S, Yamaguchi TP, Hebrok M. PMID: 19100728.
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    90. A role for von Hippel-Lindau protein in pancreatic beta-cell function. Diabetes. 2009 Feb; 58(2):433-41. Puri S, Cano DA, Hebrok M. PMID: 19033400.
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    91. Hedgehog spikes pancreas regeneration. Gastroenterology. 2008 Aug; 135(2):347-51. Cano DA, Hebrok M. PMID: 18619970.
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    92. Stabilization of beta-catenin induces pancreas tumor formation. Gastroenterology. 2008 Oct; 135(4):1288-300. Heiser PW, Cano DA, Landsman L, Kim GE, Kench JG, Klimstra DS, Taketo MM, Biankin AV, Hebrok M. PMID: 18725219.
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    93. Safer, longer-lasting regulatory T cells with beta-catenin. Nat Med. 2008 Feb; 14(2):118-9. Bluestone JA, Hebrok M. PMID: 18256611.
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    94. Regulated beta-cell regeneration in the adult mouse pancreas. Diabetes. 2008 Apr; 57(4):958-66. Cano DA, Rulifson IC, Heiser PW, Swigart LB, Pelengaris S, German M, Evan GI, Bluestone JA, Hebrok M. PMID: 18083786.
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    95. Probing cell type-specific functions of Gi in vivo identifies GPCR regulators of insulin secretion. J Clin Invest. 2007 Dec; 117(12):4034-43. Regard JB, Kataoka H, Cano DA, Camerer E, Yin L, Zheng YW, Scanlan TS, Hebrok M, Coughlin SR. PMID: 17992256.
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    96. Common activation of canonical Wnt signaling in pancreatic adenocarcinoma. PLoS One. 2007 Nov 07; 2(11):e1155. 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. PMID: 17982507.
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    97. Pancreatic innervation in mouse development and beta-cell regeneration. Neuroscience. 2007 Dec 12; 150(3):592-602. Burris RE, Hebrok M. PMID: 18006238.
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    98. A non-canonical Wnt pathway mediated by Wnt5a is required for midgut elongation. Developmental Biology. 2007 Jun 1; 306(1):419-420. Sara Cervantes, Terry P. Yamaguchi, Matthias Hebrok. .
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    99. Autonomic and sensory pancreatic nerves are differentially affected by large-scale ß-cell turnover in the RIP-cmycER mouse. Developmental Biology. 2007 Jun 1; 306(1):444. Regina E. Burris, Matthias Hebrok. .
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    100. Extracellular sulfatases, elements of the Wnt signaling pathway, positively regulate growth and tumorigenicity of human pancreatic cancer cells. PLoS One. 2007 Apr 25; 2(4):e392. Nawroth R, van Zante A, Cervantes S, McManus M, Hebrok M, Rosen SD. PMID: 17460759.
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    101. Hedgehogs: la dolce vita. Workshop on Hedgehog-Gli Signaling in Cancer and Stem Cells. EMBO Rep. 2007 May; 8(5):451-5. Robbins DJ, Hebrok M. PMID: 17431408.
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    102. Wnt signaling regulates pancreatic beta cell proliferation. Proc Natl Acad Sci U S A. 2007 Apr 10; 104(15):6247-52. Rulifson IC, Karnik SK, Heiser PW, ten Berge D, Chen H, Gu X, Taketo MM, Nusse R, Hebrok M, Kim SK. PMID: 17404238.
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    103. Sonic hedgehog acts at multiple stages during pancreatic tumorigenesis. Proc Natl Acad Sci U S A. 2007 Mar 20; 104(12):5103-8. Morton JP, Mongeau ME, Klimstra DS, Morris JP, Lee YC, Kawaguchi Y, Wright CV, Hebrok M, Lewis BC. PMID: 17372229.
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    104. Dynamics of embryonic pancreas development using real-time imaging. Dev Biol. 2007 Jun 01; 306(1):82-93. Puri S, Hebrok M. PMID: 17448459.
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    105. Liver-specific loss of beta-catenin results in delayed hepatocyte proliferation after partial hepatectomy. Hepatology. 2007 Feb; 45(2):361-8. Sekine S, Gutiérrez PJ, Lan BY, Feng S, Hebrok M. PMID: 17256747.
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    106. Pancreatic development and disease. Gastroenterology. 2007 Feb; 132(2):745-62. Cano DA, Hebrok M, Zenker M. PMID: 17258745.
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    107. Hedgehog/Ras interactions regulate early stages of pancreatic cancer. Genes Dev. 2006 Nov 15; 20(22):3161-73. Pasca di Magliano M, Sekine S, Ermilov A, Ferris J, Dlugosz AA, Hebrok M. PMID: 17114586.
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    108. Primary cilia deletion in pancreatic epithelial cells results in cyst formation and pancreatitis. Gastroenterology. 2006 Dec; 131(6):1856-69. Cano DA, Sekine S, Hebrok M. PMID: 17123526.
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    109. Stabilization of beta-catenin impacts pancreas growth. Development. 2006 May; 133(10):2023-32. Heiser PW, Lau J, Taketo MM, Herrera PL, Hebrok M. PMID: 16611688.
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    110. Liver-specific loss of beta-catenin blocks glutamine synthesis pathway activity and cytochrome p450 expression in mice. Hepatology. 2006 Apr; 43(4):817-25. Sekine S, Lan BY, Bedolli M, Feng S, Hebrok M. PMID: 16557553.
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    111. Hedgehog signaling in pancreas development and disease. Cell Mol Life Sci. 2006 Mar; 63(6):642-52. Lau J, Kawahira H, Hebrok M. PMID: 16465449.
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    112. Hedgehog Signaling in Endodermally Derived Tumors. Hedgehog-Gli Signaling in Human Disease. 2006 Jan 1; 215-224. Marina Pasca di Magliano, Matthias Hebrok. .
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    113. Hedgehog signaling regulates expansion of pancreatic epithelial cells. Dev Biol. 2005 Apr 01; 280(1):111-21. Kawahira H, Scheel DW, Smith SB, German MS, Hebrok M. PMID: 15766752.
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    114. Matrix metalloproteinases 2 and 9 are dispensable for pancreatic islet formation and function in vivo. Diabetes. 2005 Mar; 54(3):694-701. Perez SE, Cano DA, Dao-Pick T, Rougier JP, Werb Z, Hebrok M. PMID: 15734845.
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    115. Hedgehog signalling in pancreatic cancer. . 2005 Jan 1; 144:234-243. M. Hebrok. .
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    116. Orpk mouse model of polycystic kidney disease reveals essential role of primary cilia in pancreatic tissue organization. Development. 2004 Jul; 131(14):3457-67. Cano DA, Murcia NS, Pazour GJ, Hebrok M. PMID: 15226261.
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    117. Brain meets pancreas: netrin, an axon guidance molecule, controls epithelial cell migration. Trends Cell Biol. 2004 Apr; 14(4):153-5. Hebrok M, Reichardt LF. PMID: 15134068.
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    118. Development and cancer: lessons learned in the pancreas. Cell Cycle. 2004 Mar; 3(3):270-2. Heiser PW, Hebrok M. PMID: 14726662.
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    119. Hedgehog signalling in cancer formation and maintenance. Nat Rev Cancer. 2003 Dec; 3(12):903-11. Pasca di Magliano M, Hebrok M. PMID: 14737121.
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    120. Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature. 2003 Oct 23; 425(6960):851-6. 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. PMID: 14520413.
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    121. Combined activities of hedgehog signaling inhibitors regulate pancreas development. Development. 2003 Oct; 130(20):4871-9. Kawahira H, Ma NH, Tzanakakis ES, McMahon AP, Chuang PT, Hebrok M. PMID: 12917290.
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    122. Hedgehog signaling in pancreas development. Mech Dev. 2003 Jan; 120(1):45-57. Hebrok M. PMID: 12490295.
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    123. Intercellular signals regulating pancreas development and function. Genes Dev. 2001 Jan 15; 15(2):111-27. Kim SK, Hebrok M. PMID: 11157769.
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    124. Regulation of pancreas development by hedgehog signaling. Development. 2000 Nov; 127(22):4905-13. Hebrok M, Kim SK, St Jacques B, McMahon AP, Melton DA. PMID: 11044404.
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    125. Activin receptor patterning of foregut organogenesis. Genes Dev. 2000 Aug 01; 14(15):1866-71. Kim SK, Hebrok M, Li E, Oh SP, Schrewe H, Harmon EB, Lee JS, Melton DA. PMID: 10921901.
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    126. CHAPTER 6 INDUCTIVE PHENOMENA. Principles of Tissue Engineering. 2000 Jan 1; 73-80. Matthias Hebrok, Douglas A. Melton. .
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    127. Screening for novel pancreatic genes expressed during embryogenesis. Diabetes. 1999 Aug; 48(8):1550-6. Hebrok M, Kim SK, Melton DA. PMID: 10426372.
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    128. Notochord repression of endodermal Sonic hedgehog permits pancreas development. Genes Dev. 1998 Jun 01; 12(11):1705-13. Hebrok M, Kim SK, Melton DA. PMID: 9620856.
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    129. Notochord to endoderm signaling is required for pancreas development. Development. 1997 Nov; 124(21):4243-52. Kim SK, Hebrok M, Melton DA. PMID: 9334273.
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    130. Repression of muscle-specific gene activation by the murine Twist protein. Exp Cell Res. 1997 May 01; 232(2):295-303. Hebrok M, Füchtbauer A, Füchtbauer EM. PMID: 9168805.
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    131. Pancreas development in the chick embryo. Cold Spring Harb Symp Quant Biol. 1997; 62:377-83. Kim SK, Hebrok M, Melton DA. PMID: 9598372.
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    132. M-twist expression inhibits mouse embryonic stem cell-derived myogenic differentiation in vitro. Exp Cell Res. 1995 Sep; 220(1):92-100. Rohwedel J, Horák V, Hebrok M, Füchtbauer EM, Wobus AM. PMID: 7664846.
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    133. M-twist is an inhibitor of muscle differentiation. Dev Biol. 1994 Oct; 165(2):537-44. Hebrok M, Wertz K, Füchtbauer EM. PMID: 7958419.
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