Matthias Hebrok, PhD
Professor
Diabetes Center
School of Medicine
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.
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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.
Websites
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- UCSF Cancer Center (cancer.ucsf.edu)
Grants and Projects
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- Defining the role of MafA in islet beta cells, NIH, 2011-2026
- Modulating intrinsic beta cell stress to block diabetes pathogenesis, NIH, 2021-2025
- Microphysiological systems to interrogate the Islet-Liver-Adipose Axis in normal physiology and Type-2 Diabetes Mellitus, NIH, 2018-2023
- Regulation of beta cell identity and dedifferentiation, NIH, 2015-2023
- Modeling autoimmune pathogenesis and beta cell destruction by T1D immune systems, NIH, 2019-2023
- Real-time intracellular monitoring of microRNAs in human stem cell-derived insulin producing organoids, NIH, 2021-2022
- Diabetes Research Center, NIH, 2002-2021
- Using human stem cell-derived thymic epithelium to remodel T1D immune tolerance, NIH, 2016-2020
- Microphysiological systems to interrogate the Islet-Liver-Adipose Axis in normal physiology and Type-2 Diabetes Mellitus, NIH, 2018-2020
- Using human stem cell-derived thymic epithelium to remodel T1D immune tolerance, NIH/NIDDK, 2016-2020
- Epigenetic regulation of pancreatic cancer, NIH, 2014-2019
- Mechanisms of beta cell maturation, NIH, 2015-2019
- Embryonic signaling pathways in pancreatic cancer, NIH, 2004-2015
- Expanding beta-cell mass, NIH, 2010-2015
- Effects of Hedgehog Signaling on Pancreas Organogenesis, NIH, 2001-2014
- Molecular Control of Pancreatic Islet Development, NIH, 2001-2006
Publications (162)
Top publication keywords:
Cell DifferentiationPancreatic NeoplasmsHedgehog ProteinsIslets of LangerhansTrans-ActivatorsCell Transformation, NeoplasticPluripotent Stem CellsInsulin-Secreting CellsDiabetes MellitusPancreatic DuctsPancreasCell Dedifferentiationbeta CateninEmbryonic Stem CellsCarcinoma, Pancreatic Ductal
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Author Correction: Genotype tunes pancreatic ductal adenocarcinoma tissue tension to induce matricellular fibrosis and tumor progression.
Nature medicine 2024 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… -
KRAS degradation averts PDAC chemoresistance.
Nature cancer 2024 Leonhardt L, Hebrok M -
Sox9 regulates alternative splicing and pancreatic beta cell function.
Nature communications 2024 Puri S, Maachi H, Nair G, Russ HA, Chen R, Pulimeno P, Cutts Z, Ntranos V, Hebrok M -
Abstract A046: nSMase2-generated ceramide promotes PDA aggression through exosome reprogramming of the stroma.
Cancer Research 2024 Audrey M. Hendley, Atsushi Urano, Xianlu L. Peng, Sudipta Ashe, Tuan A. Phu, Martin Ng, Natanya R. Kerper, David I. Berrios, Jonghyun Lee, David Jin, Gun H. Jang, Oghenekevwe M. Gbenedio, Jeroen P. … -
Stem cell-derived islet therapy: is this the end of the beginning?
Nature reviews. Endocrinology 2023 Cochrane VA, Hebrok M
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Role of Cell-Based Therapies in T2D.
Seminars in nephrology 2023 Ashe S, Hebrok M -
Species-specific roles for the MAFA and MAFB transcription factors in regulating islet β cell identity.
JCI insight 2023 Cha J, Tong X, Walker EM, Dahan T, Cochrane VA, Ashe S, Russell R, Osipovich AB, Mawla AM, Guo M, Liu JH, Loyd ZA, Huising MO, Magnuson MA, Hebrok M, Dor Y, Stein R -
Loss of ZNF148 enhances insulin secretion in human pancreatic β cells.
JCI insight 2023 de Klerk E, Xiao Y, Emfinger CH, Keller MP, Berrios DI, Loconte V, Ekman AA, White KL, Cardone RL, Kibbey RG, Attie AD, Hebrok M -
Replenishable prevascularized cell encapsulation devices increase graft survival and function in the subcutaneous space.
Bioengineering & translational medicine 2023 Chendke GS, Kharbikar BN, Ashe S, Faleo G, Sneddon JB, Tang Q, Hebrok M, Desai TA -
Minimal SC-ß-Cell Properties for Transplantation in Diabetic Patients.
Pluripotent Stem Cell Therapy for Diabetes 2023 Veronica Cochrane, Yini Xiao, Hasna Maachi, Matthias Hebrok -
Abstract C051: Ceramide signaling regulates PDA aggression through exosome reprogramming of the stroma.
Cancer Research 2022 Audrey M. Hendley, Atsushi Urano, Xianlu L. Peng, Sudipta Ashe, Natanya R. Kerper, Tuan A. Phu, Martin Ng, Simone Giacometti, David I. Berrios, Gun H. Jang, Jen J. Yeh, Steven Gallinger, David K. … -
Multiplexed microfluidic platform for stem-cell derived pancreatic islet β cells.
Lab on a chip 2022 Goswami I, de Klerk E, Carnese P, Hebrok M, Healy KE -
Pancreatic β-Cell Development and Regeneration.
Cold Spring Harbor perspectives in biology 2022 Kerper N, Ashe S, Hebrok M -
β Cell-specific deletion of Zfp148 improves nutrient-stimulated β cell Ca2+ responses.
JCI insight 2022 Emfinger CH, de Klerk E, Schueler KL, Rabaglia ME, Stapleton DS, Simonett SP, Mitok KA, Wang Z, Liu X, Paulo JA, Yu Q, Cardone RL, Foster HR, Lewandowski SL, Perales JC, Kendziorski CM, Gygi SP, … -
Development of a Beta Cell-Specific Expression Control Element for Recombinant Adeno-Associated Virus.
Human gene therapy 2022 Chai S, Kim Y, Galivo F, Dorrell C, Wakefield L, Posey J, Ackermann AM, Kaestner KH, Hebrok M, Grompe M -
Development of a scalable method to isolate subsets of stem cell-derived pancreatic islet cells.
Stem cell reports 2022 Parent AV, Ashe S, Nair GG, Li ML, Chavez J, Liu JS, Zhong Y, Streeter PR, Hebrok M -
Transcriptional changes and the role of ONECUT1 in hPSC pancreatic differentiation.
Communications biology 2021 Heller S, Li Z, Lin Q, Geusz R, Breunig M, Hohwieler M, Zhang X, Nair GG, Seufferlein T, Hebrok M, Sander M, Julier C, Kleger A, Costa IG -
Abstract PR-008: Kdm6 demethylases are critical regulators of pancreatic cancer initiation, progression and subtype specification.
Cancer Research 2021 Laura Leonhardt, Lucia Y. Li, David I. Berrios, Sudipta Ashe, Audrey M. Hendley, Grace E. Kim, Matthias Hebrok -
Mutations and variants of ONECUT1 in diabetes.
Nature medicine 2021 Philippi A, Heller S, Costa IG, Senée V, Breunig M, Li Z, Kwon G, Russell R, Illing A, Lin Q, Hohwieler M, Degavre A, Zalloua P, Liebau S, Schuster M, Krumm J, Zhang X, Geusz R, Benthuysen JR, Wang A,… -
Selective deletion of human leukocyte antigens protects stem cell-derived islets from immune rejection.
Cell reports 2021 Parent AV, Faleo G, Chavez J, Saxton M, Berrios DI, Kerper NR, Tang Q, Hebrok M -
Superporous agarose scaffolds for encapsulation of adult human islets and human stem-cell-derived β cells for intravascular bioartificial pancreas applications.
Journal of biomedical materials research. Part A 2021 Shaheen R, Gurlin RE, Gologorsky R, Blaha C, Munnangi P, Santandreu A, Torres A, Carnese P, Nair GG, Szot G, Fissell WH, Hebrok M, Roy S -
Single-cell transcriptome analysis defines heterogeneity of the murine pancreatic ductal tree.
eLife 2021 Hendley AM, Rao AA, Leonhardt L, Ashe S, Smith JA, Giacometti S, Peng XL, Jiang H, Berrios DI, Pawlak M, Li LY, Lee J, Collisson EA, Anderson MS, Fragiadakis GK, Yeh JJ, Ye CJ, Kim GE, Weaver VM, … -
Stem Cell-Based Clinical Trials for Diabetes Mellitus.
Frontiers in endocrinology 2021 de Klerk E, Hebrok M -
Non-xenogeneic expansion and definitive endoderm differentiation of human pluripotent stem cells in an automated bioreactor.
Biotechnology and bioengineering 2020 Jacobson EF, Chen Z, Stoukides DM, Nair GG, Hebrok M, Tzanakakis ES -
Emerging routes to the generation of functional β-cells for diabetes mellitus cell therapy.
Nature reviews. Endocrinology 2020 Nair GG, Tzanakakis ES, Hebrok M -
Loss of the transcription factor MAFB limits β-cell derivation from human PSCs.
Nature communications 2020 Russell R, Carnese PP, Hennings TG, Walker EM, Russ HA, Liu JS, Giacometti S, Stein R, Hebrok M -
LIN28B Impairs the Transition of hESC-Derived β Cells from the Juvenile to Adult State.
Stem cell reports 2019 Zhou X, Nair GG, Russ HA, Belair CD, Li ML, Shveygert M, Hebrok M, Blelloch R -
Abstract C20: Smpd3 augments chemotherapy and thwarts PDA progression.
Cancer Research 2019 Audrey M. Hendley, Atsushi Urano, Natanya R. Kerper, Phat Duong, Peter Bailey, David K. Chang, Andrew V. Biankin, David W. Dawson, Grace Kim, Robert L. Raffai, Matthias Hebrok -
Lipid Droplet Accumulation in Human Pancreatic Islets Is Dependent On Both Donor Age and Health.
Diabetes 2019 Tong X, Dai C, Walker JT, Nair GG, Kennedy A, Carr RM, Hebrok M, Powers AC, Stein R -
Using a barcoded AAV capsid library to select for clinically relevant gene therapy vectors.
JCI insight 2019 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 -
Supporting Survival of Transplanted Stem-Cell-Derived Insulin-Producing Cells in an Encapsulation Device Augmented with Controlled Release of Amino Acids.
Advanced biosystems 2019 Chendke GS, Faleo G, Juang C, Parent AV, Bernards DA, Hebrok M, Tang Q, Desai TA -
mTORC1 to AMPK switching underlies β-cell metabolic plasticity during maturation and diabetes.
The Journal of clinical investigation 2019 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 -
The Pdx1-Bound Swi/Snf Chromatin Remodeling Complex Regulates Pancreatic Progenitor Cell Proliferation and Mature Islet β-Cell Function.
Diabetes 2019 Spaeth JM, Liu JH, Peters D, Guo M, Osipovich AB, Mohammadi F, Roy N, Bhushan A, Magnuson MA, Hebrok M, Wright CVE, Stein R -
Author Correction: Recapitulating endocrine cell clustering in culture promotes maturation of human stem-cell-derived β cells.
Nature cell biology 2019 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 -
Pancreatic pericytes originate from the embryonic pancreatic mesenchyme.
Developmental biology 2019 Harari N, Sakhneny L, Khalifa-Malka L, Busch A, Hertel KJ, Hebrok M, Landsman L -
Rapid generation of functional mature pancreatic islet-beta cells from human pluripotent stem cells.
Protocol Exchange 2019 Gopika Nair, Gopika Nair, Holger Russ, Matthias Hebrok -
Recapitulating endocrine cell clustering in culture promotes maturation of human stem-cell-derived β cells.
Nature cell biology 2019 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 -
The BRG1/SOX9 axis is critical for acinar cell-derived pancreatic tumorigenesis.
The Journal of clinical investigation 2018 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 … -
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 Gaetano Faleo, Casey Ward, Audrey Parent, Gopika Nair, Wenhan Chang, Peter Stock, Matthias Hebrok, Qizhi Tang -
Stem Cell Therapies for Treating Diabetes: Progress and Remaining Challenges.
Cell stem cell 2018 Sneddon JB, Tang Q, Stock P, Bluestone JA, Roy S, Desai T, Hebrok M -
Synaptotagmin 4 Regulates Pancreatic β Cell Maturation by Modulating the Ca2+ Sensitivity of Insulin Secretion Vesicles.
Developmental cell 2018 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 -
Replication confers β cell immaturity.
Nature communications 2018 Puri S, Roy N, Russ HA, Leonhardt L, French EK, Roy R, Bengtsson H, Scott DK, Stewart AF, Hebrok M -
Mitigating Ischemic Injury of Stem Cell-Derived Insulin-Producing Cells after Transplant.
Stem cell reports 2017 Faleo G, Russ HA, Wisel S, Parent AV, Nguyen V, Nair GG, Freise JE, Villanueva KE, Szot GL, Hebrok M, Tang Q -
Nanoporous Immunoprotective Device for Stem-Cell-Derived β-Cell Replacement Therapy.
ACS nano 2017 Chang R, Faleo G, Russ HA, Parent AV, Elledge SK, Bernards DA, Allen JL, Villanueva K, Hebrok M, Tang Q, Desai TA -
Corticotropin-releasing hormone type 2 receptor deficiency impairs pancreatic function in a sex-specific manner.
Pancreatology 2017 Aditi Bhargava, Shinichiro Hagiwara, Sapna Puri, Matthias Hebrok, Gregory Szot, Burcu Hasdemir, Sreenivasan Paruthiyil -
Atypical flat lesions derive from pancreatic acinar cells.
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 2017 von Figura G, Fahrenkrog-Petersen L, Hidalgo-Sastre A, Hartmann D, Hüser N, Schmid RM, Hebrok M, Roy N, Esposito I -
Global Protease Activity Profiling Provides Differential Diagnosis of Pancreatic Cysts.
Clinical cancer research : an official journal of the American Association for Cancer Research 2017 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 -
Global Protease Activity Profiling Provides Differential Diagnosis of Cystic Precursor Lesions of Pancreatic Cancer.
The FASEB Journal 2017 Sam Lacey Ivry, Dana Dominguez, Nilotpal Roy, Stacy Hatcher, Matthias Hebrok, Grace Kim, Anthony O'Donoghue, Kim Kirkwood, Charles Craik -
Designing β Cells.
Cell metabolism 2017 Hebrok M -
All mixed up: defining roles for β-cell subtypes in mature islets.
Genes & development 2017 Liu JS, Hebrok M -
Abstract A50: Genotype tunes PDAC tension to induce matricellular-fibrosis and tumor aggression.
Early Detection 2016 Hanane Laklai, Yekaterina Miroshnikova, Michael Pickup, Eric Collisson, Kim Grace, Alex Barrett, Ryan Hill, Johnathon Lakins, David Schlaepfer, Janna Mouw, Valerie LeBleu, Sergey Novitskiy, Julie … -
PDX1 dynamically regulates pancreatic ductal adenocarcinoma initiation and maintenance.
Genes & development 2016 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 -
Rebranding asymptomatic type 1 diabetes: the case for autoimmune beta cell disorder as a pathological and diagnostic entity.
Diabetologia 2016 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 -
Loss of Pancreas upon Activated Wnt Signaling Is Concomitant with Emergence of Gastrointestinal Identity.
PloS one 2016 Muñoz-Bravo JL, Flores-Martínez A, Herrero-Martin G, Puri S, Taketo MM, Rojas A, Hebrok M, Cano DA -
Human islets contain four distinct subtypes of β cells.
Nature communications 2016 Dorrell C, Schug J, Canaday PS, Russ HA, Tarlow BD, Grompe MT, Horton T, Hebrok M, Streeter PR, Kaestner KH, Grompe M -
Genotype tunes pancreatic ductal adenocarcinoma tissue tension to induce matricellular fibrosis and tumor progression.
Nature medicine 2016 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… -
p120 Catenin Suppresses Basal Epithelial Cell Extrusion in Invasive Pancreatic Neoplasia.
Cancer research 2016 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 -
Life and death of β cells in Type 1 diabetes: A comprehensive review.
Journal of autoimmunity 2016 Wilcox NS, Rui J, Hebrok M, Herold KC -
A functional circadian clock is required for proper insulin secretion by human pancreatic islet cells.
Diabetes, obesity & metabolism 2016 Saini C, Petrenko V, Pulimeno P, Giovannoni L, Berney T, Hebrok M, Howald C, Dermitzakis ET, Dibner C -
Human pancreatic beta-like cells converted from fibroblasts.
Nature communications 2016 Zhu S, Russ HA, Wang X, Zhang M, Ma T, Xu T, Tang S, Hebrok M, Ding S -
Chapter 30 Development of the Endocrine Pancreas.
Endocrinology: Adult and Pediatric 2016 Matthias Hebrok, Michael S. German -
Regulation of Cellular Identity in Cancer.
Developmental cell 2015 Roy N, Hebrok M -
β-Cell Insulin Secretion Requires the Ubiquitin Ligase COP1.
Cell 2015 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 -
Dynamic Proteomic Analysis of Pancreatic Mesenchyme Reveals Novel Factors That Enhance Human Embryonic Stem Cell to Pancreatic Cell Differentiation.
Stem cells international 2015 Russ HA, Landsman L, Moss CL, Higdon R, Greer RL, Kaihara K, Salamon R, Kolker E, Hebrok M -
Human stem cells from single blastomeres reveal pathways of embryonic or trophoblast fate specification.
Development (Cambridge, England) 2015 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 … -
DNA methylation directs functional maturation of pancreatic β cells.
The Journal of clinical investigation 2015 Dhawan S, Tschen SI, Zeng C, Guo T, Hebrok M, Matveyenko A, Bhushan A -
Controlled induction of human pancreatic progenitors produces functional beta-like cells in vitro.
The EMBO journal 2015 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 -
Islet formation in mice and men: lessons for the generation of functional insulin-producing β-cells from human pluripotent stem cells.
Current opinion in genetics & development 2015 Nair G, Hebrok M -
Brg1 promotes both tumor-suppressive and oncogenic activities at distinct stages of pancreatic cancer formation.
Genes & development 2015 Roy N, Malik S, Villanueva KE, Urano A, Lu X, Von Figura G, Seeley ES, Dawson DW, Collisson EA, Hebrok M -
CDK1 inhibition targets the p53-NOXA-MCL1 axis, selectively kills embryonic stem cells, and prevents teratoma formation.
Stem cell reports 2015 Huskey NE, Guo T, Evason KJ, Momcilovic O, Pardo D, Creasman KJ, Judson RL, Blelloch R, Oakes SA, Hebrok M, Goga A -
NFATc1 Links EGFR Signaling to Induction of Sox9 Transcription and Acinar-Ductal Transdifferentiation in the Pancreas.
Gastroenterology 2015 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 -
Antithetical NFATc1-Sox2 and p53-miR200 signaling networks govern pancreatic cancer cell plasticity.
The EMBO journal 2015 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, … -
Plasticity and dedifferentiation within the pancreas: development, homeostasis, and disease.
Cell stem cell 2014 Puri S, Folias AE, Hebrok M -
Taming the young and restless--epigenetic gene regulation in pancreas and beta-cell precursors.
The EMBO journal 2014 Russ HA, Hebrok M -
Aberrant innate immune activation following tissue injury impairs pancreatic regeneration.
PloS one 2014 Folias AE, Penaranda C, Su AL, Bluestone JA, Hebrok M -
Dicer regulates differentiation and viability during mouse pancreatic cancer initiation.
PloS one 2014 Morris JP, Greer R, Russ HA, von Figura G, Kim GE, Busch A, Lee J, Hertel KJ, Kim S, McManus M, Hebrok M -
Generation of insulin-producing cells from human stem cells (207.3).
The FASEB Journal 2014 Matthias Hebrok -
Analyzing pancreas development with the goal to generate functional ß-cells from stem cells and prevent neoplastic transformation.
Pancreatology 2014 Matthias Hebrok -
Diabetes. Solving human β-cell development--what does the mouse say?
Nature reviews. Endocrinology 2014 Folias AE, Hebrok M -
The chromatin regulator Brg1 suppresses formation of intraductal papillary mucinous neoplasm and pancreatic ductal adenocarcinoma.
Nature cell biology 2014 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 -
Small molecules facilitate the reprogramming of mouse fibroblasts into pancreatic lineages.
Cell stem cell 2014 Li K, Zhu S, Russ HA, Xu S, Xu T, Zhang Y, Ma T, Hebrok M, Ding S -
Overview.
Metabolism of Human Diseases 2014 Alexandra E. Folias, Matthias Hebrok -
VHL-mediated disruption of Sox9 activity compromises β-cell identity and results in diabetes mellitus.
Genes & development 2013 Puri S, Akiyama H, Hebrok M -
Elimination of von Hippel-Lindau function perturbs pancreas endocrine homeostasis in mice.
PloS one 2013 Puri S, García-Núñez A, Hebrok M, Cano DA -
Numb regulates acinar cell dedifferentiation and survival during pancreatic damage and acinar-to-ductal metaplasia.
Gastroenterology 2013 Greer RL, Staley BK, Liou A, Hebrok M -
Canonical wnt signaling is required for pancreatic carcinogenesis.
Cancer research 2013 Zhang Y, Morris JP, Yan W, Schofield HK, Gurney A, Simeone DM, Millar SE, Hoey T, Hebrok M, Pasca di Magliano M -
Control of cell identity in pancreas development and regeneration.
Gastroenterology 2013 Stanger BZ, Hebrok M -
Generation of functional thymic epithelium from human embryonic stem cells that supports host T cell development.
Cell stem cell 2013 Parent AV, Russ HA, Khan IS, LaFlam TN, Metzger TC, Anderson MS, Hebrok M -
Nr5a2 maintains acinar cell differentiation and constrains oncogenic Kras-mediated pancreatic neoplastic initiation.
Gut 2013 von Figura G, Morris JP, Wright CV, Hebrok M -
Dormant cancer cells contribute to residual disease in a model of reversible pancreatic cancer.
Cancer research 2013 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 -
Factors expressed by murine embryonic pancreatic mesenchyme enhance generation of insulin-producing cells from hESCs.
Diabetes 2013 Guo T, Landsman L, Li N, Hebrok M -
Identification of Sox9-dependent acinar-to-ductal reprogramming as the principal mechanism for initiation of pancreatic ductal adenocarcinoma.
Cancer cell 2012 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 -
Advances in acute and chronic pancreatitis: from development to inflammation and repair.
Gastroenterology 2012 Pasca di Magliano M, Forsmark C, Freedman S, Hebrok M, Pasricha PJ, Saluja A, Stanger BZ, Holt J, Serrano J, James SP, Rustgi AK -
Diabetic β Cells: To Be or Not To Be?
Cell 2012 Puri S, Hebrok M -
Generating β cells from stem cells-the story so far.
Cold Spring Harbor perspectives in medicine 2012 Hebrok M -
Bmi1 is required for regeneration of the exocrine pancreas in mice.
Gastroenterology 2012 Fukuda A, Morris JP, Hebrok M -
Abstract LB-429: Dormant cancer cells contribute to residual disease in a mouse model for reversible pancreatic cancer.
Tumor Biology 2012 Wan-Chi Lin, Nirakar Rajbhandari, Chengbao Liu, Kazuhito Sakamoto, Surinder Batra, Rene Opavsky, Dean Felsher, Michael Hollingsworth, Matthias Hebrok, Hallgeir Rui, Kay-Uwe Wagner -
Transcriptional analysis of pluripotency reveals the Hippo pathway as a barrier to reprogramming.
Human molecular genetics 2012 Qin H, Blaschke K, Wei G, Ohi Y, Blouin L, Qi Z, Yu J, Yeh RF, Hebrok M, Ramalho-Santos M -
Elevated Hedgehog/Gli signaling causes beta-cell dedifferentiation in mice.
Proceedings of the National Academy of Sciences of the United States of America 2011 Landsman L, Parent A, Hebrok M -
Pancreatic mesenchyme regulates epithelial organogenesis throughout development.
PLoS biology 2011 Landsman L, Nijagal A, Whitchurch TJ, Vanderlaan RL, Zimmer WE, Mackenzie TC, Hebrok M -
How does type 1 diabetes develop?: the notion of homicide or β-cell suicide revisited.
Diabetes 2011 Atkinson MA, Bluestone JA, Eisenbarth GS, Hebrok M, Herold KC, Accili D, Pietropaolo M, Arvan PR, Von Herrath M, Markel DS, Rhodes CJ -
Incomplete DNA methylation underlies a transcriptional memory of somatic cells in human iPS cells.
Nature cell biology 2011 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 -
Stat3 and MMP7 contribute to pancreatic ductal adenocarcinoma initiation and progression.
Cancer cell 2011 Fukuda A, Wang SC, Morris JP, Folias AE, Liou A, Kim GE, Akira S, Boucher KM, Firpo MA, Mulvihill SJ, Hebrok M -
KRAS, Hedgehog, Wnt and the twisted developmental biology of pancreatic ductal adenocarcinoma.
Nature reviews. Cancer 2010 Morris JP, Wang SC, Hebrok M -
Stat3 and MMP7 mediate multiple aspects of pancreatic ductal adenocarcinoma biology.
Journal of the American College of Surgeons 2010 Sam C. Wang, Akihisa Fukuda, John P. Morris, Angela Liou, Shizuo Akira, Matthias Hebrok -
Dynamic switch of negative feedback regulation in Drosophila Akt-TOR signaling.
PLoS genetics 2010 Kockel L, Kerr KS, Melnick M, Brückner K, Hebrok M, Perrimon N -
Primary cilia regulate Gli/Hedgehog activation in pancreas.
Proceedings of the National Academy of Sciences of the United States of America 2010 Cervantes S, Lau J, Cano DA, Borromeo-Austin C, Hebrok M -
Cellular plasticity within the pancreas--lessons learned from development.
Developmental cell 2010 Puri S, Hebrok M -
Hedgehog signaling in pancreas epithelium regulates embryonic organ formation and adult beta-cell function.
Diabetes 2010 Lau J, Hebrok M -
Beta-catenin blocks Kras-dependent reprogramming of acini into pancreatic cancer precursor lesions in mice.
The Journal of clinical investigation 2010 Morris JP, Cano DA, Sekine S, Wang SC, Hebrok M -
Chapter 31 Development of the Endocrine Pancreas.
2010 Matthias Hebrok, Michael S. German -
Hedgehog Signaling Pathways in Pancreatic Cancer Pathogenesis.
Pancreatic Cancer 2010 Marina Pasca di Magliano, Matthias Hebrok -
It's a free for all--insulin-positive cells join the group of potential progenitors for pancreatic ductal adenocarcinoma.
Cancer cell 2009 Morris JP, Hebrok M -
Dicer is required for proper liver zonation.
The Journal of pathology 2009 Sekine S, Ogawa R, Mcmanus MT, Kanai Y, Hebrok M -
Stem cells to pancreatic beta-cells: new sources for diabetes cell therapy.
Endocrine reviews 2009 Guo T, Hebrok M -
Disruption of Dicer1 induces dysregulated fetal gene expression and promotes hepatocarcinogenesis.
Gastroenterology 2009 Sekine S, Ogawa R, Ito R, Hiraoka N, McManus MT, Kanai Y, Hebrok M -
GLI1 is regulated through Smoothened-independent mechanisms in neoplastic pancreatic ducts and mediates PDAC cell survival and transformation.
Genes & development 2009 Nolan-Stevaux O, Lau J, Truitt ML, Chu GC, Hebrok M, Fernández-Zapico ME, Hanahan D -
Wnt5a is essential for intestinal elongation in mice.
Developmental biology 2008 Cervantes S, Yamaguchi TP, Hebrok M -
A role for von Hippel-Lindau protein in pancreatic beta-cell function.
Diabetes 2008 Puri S, Cano DA, Hebrok M -
Hedgehog spikes pancreas regeneration.
Gastroenterology 2008 Cano DA, Hebrok M -
Stabilization of beta-catenin induces pancreas tumor formation.
Gastroenterology 2008 Heiser PW, Cano DA, Landsman L, Kim GE, Kench JG, Klimstra DS, Taketo MM, Biankin AV, Hebrok M -
Safer, longer-lasting regulatory T cells with beta-catenin.
Nature medicine 2008 Bluestone JA, Hebrok M -
Regulated beta-cell regeneration in the adult mouse pancreas.
Diabetes 2007 Cano DA, Rulifson IC, Heiser PW, Swigart LB, Pelengaris S, German M, Evan GI, Bluestone JA, Hebrok M -
Probing cell type-specific functions of Gi in vivo identifies GPCR regulators of insulin secretion.
The Journal of clinical investigation 2007 Regard JB, Kataoka H, Cano DA, Camerer E, Yin L, Zheng YW, Scanlan TS, Hebrok M, Coughlin SR -
Common activation of canonical Wnt signaling in pancreatic adenocarcinoma.
PloS one 2007 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 -
Pancreatic innervation in mouse development and beta-cell regeneration.
Neuroscience 2007 Burris RE, Hebrok M -
A non-canonical Wnt pathway mediated by Wnt5a is required for midgut elongation.
Developmental Biology 2007 Sara Cervantes, Terry P. Yamaguchi, Matthias Hebrok -
Autonomic and sensory pancreatic nerves are differentially affected by large-scale ß-cell turnover in the RIP-cmycER mouse.
Developmental Biology 2007 Regina E. Burris, Matthias Hebrok -
Extracellular sulfatases, elements of the Wnt signaling pathway, positively regulate growth and tumorigenicity of human pancreatic cancer cells.
PloS one 2007 Nawroth R, van Zante A, Cervantes S, McManus M, Hebrok M, Rosen SD -
Hedgehogs: la dolce vita. Workshop on Hedgehog-Gli Signaling in Cancer and Stem Cells.
EMBO reports 2007 Robbins DJ, Hebrok M -
Wnt signaling regulates pancreatic beta cell proliferation.
Proceedings of the National Academy of Sciences of the United States of America 2007 Rulifson IC, Karnik SK, Heiser PW, ten Berge D, Chen H, Gu X, Taketo MM, Nusse R, Hebrok M, Kim SK -
Sonic hedgehog acts at multiple stages during pancreatic tumorigenesis.
Proceedings of the National Academy of Sciences of the United States of America 2007 Morton JP, Mongeau ME, Klimstra DS, Morris JP, Lee YC, Kawaguchi Y, Wright CV, Hebrok M, Lewis BC -
Dynamics of embryonic pancreas development using real-time imaging.
Developmental biology 2007 Puri S, Hebrok M -
Liver-specific loss of beta-catenin results in delayed hepatocyte proliferation after partial hepatectomy.
Hepatology (Baltimore, Md.) 2007 Sekine S, Gutiérrez PJ, Lan BY, Feng S, Hebrok M -
Pancreatic development and disease.
Gastroenterology 2007 Cano DA, Hebrok M, Zenker M -
Hedgehog/Ras interactions regulate early stages of pancreatic cancer.
Genes & development 2006 Pasca di Magliano M, Sekine S, Ermilov A, Ferris J, Dlugosz AA, Hebrok M -
Primary cilia deletion in pancreatic epithelial cells results in cyst formation and pancreatitis.
Gastroenterology 2006 Cano DA, Sekine S, Hebrok M -
Stabilization of beta-catenin impacts pancreas growth.
Development (Cambridge, England) 2006 Heiser PW, Lau J, Taketo MM, Herrera PL, Hebrok M -
Liver-specific loss of beta-catenin blocks glutamine synthesis pathway activity and cytochrome p450 expression in mice.
Hepatology (Baltimore, Md.) 2006 Sekine S, Lan BY, Bedolli M, Feng S, Hebrok M -
Hedgehog signaling in pancreas development and disease.
Cellular and molecular life sciences : CMLS 2006 Lau J, Kawahira H, Hebrok M -
Hedgehog Signaling in Endodermally Derived Tumors.
Hedgehog-Gli Signaling in Human Disease 2006 Marina Pasca di Magliano, Matthias Hebrok -
Hedgehog signaling regulates expansion of pancreatic epithelial cells.
Developmental biology 2005 Kawahira H, Scheel DW, Smith SB, German MS, Hebrok M -
Matrix metalloproteinases 2 and 9 are dispensable for pancreatic islet formation and function in vivo.
Diabetes 2005 Perez SE, Cano DA, Dao-Pick T, Rougier JP, Werb Z, Hebrok M -
Hedgehog signalling in pancreatic cancer.
2005 M. Hebrok -
Orpk mouse model of polycystic kidney disease reveals essential role of primary cilia in pancreatic tissue organization.
Development (Cambridge, England) 2004 Cano DA, Murcia NS, Pazour GJ, Hebrok M -
Brain meets pancreas: netrin, an axon guidance molecule, controls epithelial cell migration.
Trends in cell biology 2004 Hebrok M, Reichardt LF -
Development and cancer: lessons learned in the pancreas.
Cell cycle (Georgetown, Tex.) 2004 Heiser PW, Hebrok M -
Hedgehog signalling in cancer formation and maintenance.
Nature reviews. Cancer 2003 Pasca di Magliano M, Hebrok M -
Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis.
Nature 2003 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 -
Combined activities of hedgehog signaling inhibitors regulate pancreas development.
Development (Cambridge, England) 2003 Kawahira H, Ma NH, Tzanakakis ES, McMahon AP, Chuang PT, Hebrok M -
Hedgehog signaling in pancreas development.
Mechanisms of development 2003 Hebrok M -
Intercellular signals regulating pancreas development and function.
Genes & development 2001 Kim SK, Hebrok M -
Regulation of pancreas development by hedgehog signaling.
Development (Cambridge, England) 2000 Hebrok M, Kim SK, St Jacques B, McMahon AP, Melton DA -
Activin receptor patterning of foregut organogenesis.
Genes & development 2000 Kim SK, Hebrok M, Li E, Oh SP, Schrewe H, Harmon EB, Lee JS, Melton DA -
CHAPTER 6 INDUCTIVE PHENOMENA.
Principles of Tissue Engineering 2000 Matthias Hebrok, Douglas A. Melton -
Screening for novel pancreatic genes expressed during embryogenesis.
Diabetes 1999 Hebrok M, Kim SK, Melton DA -
Notochord repression of endodermal Sonic hedgehog permits pancreas development.
Genes & development 1998 Hebrok M, Kim SK, Melton DA -
Notochord to endoderm signaling is required for pancreas development.
Development (Cambridge, England) 1997 Kim SK, Hebrok M, Melton DA -
Repression of muscle-specific gene activation by the murine Twist protein.
Experimental cell research 1997 Hebrok M, Füchtbauer A, Füchtbauer EM -
Pancreas development in the chick embryo.
Cold Spring Harbor symposia on quantitative biology 1997 Kim SK, Hebrok M, Melton DA -
M-twist expression inhibits mouse embryonic stem cell-derived myogenic differentiation in vitro.
Experimental cell research 1995 Rohwedel J, Horák V, Hebrok M, Füchtbauer EM, Wobus AM -
M-twist is an inhibitor of muscle differentiation.
Developmental biology 1994 Hebrok M, Wertz K, Füchtbauer EM