Biomedical Sciences Graduate Program | University of California, San Francisco

Matthias Hebrok, PhD
Molecular mechanisms of pancreas development, function and disease

Selected Publications | Complete Publications

phone	(415) 514-0820
email	mhebrok@diabetes.ucsf.edu
additional websites	Lab Website Diabetes Center Program in Biological Sciences Developmental Biology Dept of Medicine
secondary research affiliation	Cancer Biology & Cell Signaling

My laboratory uses Cell, Molecular, and Developmental Biology tools to decipher the mechanisms that underlie normal mammalian pancreas formation and pancreatic diseases, including diabetes and pancreatic cancer. In particular, we are focusing on the role of embryonic signaling pathways, including Hedgehog and Wnt signaling, during pancreas formation and function. We are using state of the art tools, including transgenic mice and small chemical compounds, to manipulate the activity of these pathways during pancreas formation and in mature tissue. The goal of these studies is to determine whether controlled activation and de-activation of embryonic signaling pathways permits a) to initiate the formation of insulin-producing ß-cells from uncommitted stem cell progenitors, e.g. embryonic and adult stem cells, and b) to prevent the formation and growth of pancreatic tumors.

Selected Publications

Hebrok, M., Wertz, K. and E.-M. Füchtbauer (1994): M-twist is an inhibitor of muscle differentiation. Dev. Biol. 165, 537-544.

Rohwedel, J., Horak, V., Füchtbauer, E.-M., Hebrok, M. and A. M. Wobus (1995): M-twist expression inhibits mouse embryonic stem cell-derived myogenic differentiation in vitro. Exp. Cell Res. 220, 92-100.

Hebrok, M., Füchtbauer, A. and E.-M. Füchtbauer (1997): Repression of muscle-specific gene activation by the murine twist protein. Exp. Cell Res. 232, 295-303.

Kim, S. K., Hebrok, M. and D. A. Melton (1997): Notochord to endoderm signaling is required for pancreas development. Development 124, 4243-4252.

Kim, S. K., Hebrok, M. and D. A. Melton (1997): Pancreas development in the chick embryo. Cold Spring Harbour Symp. Quant. Biol. 62, 377-383.

Hebrok, M., Kim, S. K. and D. A. Melton (1998): Notochord repression of endodermal Sonic hedgehog permits pancreas development. Genes & Development 12, 1705-1713.

Hebrok, M., Kim, S. K. and D. A. Melton (1999): Screening for novel pancreatic genes expressed during embryogenesis. Diabetes 48, 1550-1556.

Kim, S. K., Hebrok, M., Li, E., Oh, P., Schrewe, H., Harmon, E. B., Lee, J. S. and D. A. Melton. (2000): Activin receptor patterning of foregut organogenesis. Genes & Development 14, 1866-1871.

Hebrok, M., Kim, S. K., St-Jacques, B., McMahon A. P. and D. A. Melton. (2000): Regulation of pancreas development by Hedgehog signaling. Development 127, 4905-4913.

Kim, S. K. and Hebrok, M. (2001): Intercellular signals regulating pancreas development and function. Genes & Development 15, 111-127.

Hebrok, M. (2003): Hedgehog signaling in pancreas development, Mech. Dev. 120, 45-57.

Kawahira, H., Tzanakakis, E., Ma, N., McMahon, A. P., Chuang, P.-T., and M. Hebrok (2003): Combined activities of Hedgehog signaling inhibitors regulate pancreas development. Development 130, 4871-4879.

Thayer, S. P., Pasca di Magliano, M., Heiser, P.W., Roberts, D. J., Nielsen, C. M., Lauwers, G. Y., Qi, Y.P., Gysin, S., Fernandez-del Castillo, F., Yajnik, V., Antoniu, B., McMahon, M., Warshaw, A. L., and M. Hebrok (2003): Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature 425, 851 - 856.

Pasca di Magliano, M., and M. Hebrok (2003): Hedgehog signalling in cancer formation and maintenance. Nature Reviews Cancer 3, 903-911.

Heiser, P. W. and M. Hebrok (2004): Development and cancer: Lessons learned in the pancreas. Cell Cycle 3, 270 -272.
Hebrok, M. and L. F. Reichardt (2004): Brain meets pancreas: netrin, an axon guidance molecule, controls epithelial cell migration. Trends in Cell Biology 14, 153-155.

Cano, D. A., Murcia, N. S., Pazour, G. J. and M. Hebrok (2004): Orpk mouse model of polycystic kidney disease reveals essential role of primary cilia in pancreatic tissue organization. Development 131, 3457-3467.

Kawahira, H., Scheel. D. W., Smith, S. B., German, M. S., and M. Hebrok (2005): Hedgehog signaling regulates expansion of pancreatic epithelial cells. Dev. Bio. 280, 111-121.

Perez, S. Cano, D. A., Dao-Pick, T., Rougier, V., Werb, Z., and M. Hebrok (2005) Matrix Metalloproteinase 2 and 9 are dispensable for pancreatic islet formation and function in vivo. Diabetes 54, 694-701.

Lau, J., Kawahira, H., and M. Hebrok (2006): Hedgehog signaling in pancreas development and disease. Cellular and Molecular Life Sciences 63, 642-52.

Heiser, P. W., Lau, J. Taketo, M., Herrera P., and M. Hebrok (2006): Stabilization of b-catenin impacts pancreas growth. Development 133, 2023-2032.

Sekine, S., Lan, B., Bedolli, M., Feng, S. and M. Hebrok (2006): Liver-specific loss of ß-catenin blocks glutamine synthesis pathway activity and cytochrome p450 expression in mice. Hepatology 43, 817-825.

Pasca di Magliano, M. Sekine, S., Ermilov, A. Brown, J. Dlugosz, A.A., and M. Hebrok (2006): Hedgehog/Ras interactions regulate early stages of pancreatic cancer. Genes & Development 20, 3161-3173.

Cano D. A., Sekine S. and M. Hebrok (2006): Primary cilia deletion in pancreatic epithelial cells results in cyst formation and pancreatitis. Gastroenterology 131 (6):1856-69. Epub 2006 Oct 26.

Sekine, S., Gutierrez, P. J. A., Lan, B. M., Feng, S. and M. Hebrok (2007): Liver-specific loss of beta-catenin results in delayed hepatocyte proliferation after partial hepatectomy. Hepatology 45 (2):361-368 [Epub ahead of print].

Cano, D. A., Hebrok, M., and M. Zenker (2007): Pancreatic development and disease. Gastroenterology 132, 745-762.

Morton, J.P., Mongeau, M.E., Morris, J.P., Klimstra, D.S., Lee, Y.C., Kawaguchi, Y., Wright, C.V.E., Hebrok, M., and B. C. Lewis (2007): Sonic hedgehog acts at multiple stages during pancreatic tumorigenesis. PNAS 104, 5103-5108.

Rulifson, I. C., Heiser, P., Karnik, S. K., ten Berge, D., Gu, X., Taketo, M., Nusse, R., Hebrok, M., and Seung K. Kim (2006): Wnt signaling regulates pancreatic ß-cell proliferation. PNAS 104, 6247-6352.

Robbins, D. J. and M. Hebrok (2007): Hedgehogs: La Dolce Vita. EMBO Reports 8, 451-455.

Puri, S. and M. Hebrok (2007): Dynamics of embryonic pancreas development using real-time imaging, Dev. Biol. 306(1):82-93, Mar 12; [Epub ahead of print].

Nawroth, R., Cervantes, S., McManus, M., Hebrok, M. and S. D. Rosen (2007): Extracellular sulfatases, elements of the wnt signaling pathway, positively regulate growth and tumorigenicity of human pancreatic cancer cells. PLoS ONE 2007 Apr 25;2:e392.

Pasca di Magliano, M. Biankin, A. V., Heiser, P. W., Cano, D. A., Gutierrez, P. J. A., Deramaudt, T., Segara, D., Dawson, A. C., Kench, J. G., Henshall, S. M., Sutherland, R. L., Dlugosz, A., Rustgi, A. K., and M. Hebrok (2007): Wnt signaling in pancreatic cancer. PLoS ONE 2(11): e1155. oi:10.1371/journal.pone.0001155.

Lee, J., Wu, X., Pasca di Magliano, M., Peters, E. C., Wang, Y., Hong, J., Hebrok, M., Ding, S., Cho, C. Y. and P. G. Schultz. (2007): A Small Molecule Antagonist of the Hedgehog Signaling Pathway. ChemBioChem 8 (16):1916-1919.

Burris, R. and M. Hebrok (2007): Pancreatic innervation in mouse development and ß-cell regeneration. Neuroscience 150 (3):592-602. Epub 2007 Oct 11.

Regard. J., Kataoka, H., Cano, D., Camerer, E., Yin, L., Zheng, Y.-W., Dolganov, G., Kobilka, B., Scanlan, T., Hebrok, M. and S. R. Coughlin (2007): Probing cell type specific functions of Gi signaling in vivo identifies novel regulators of insulin secretion. Journal of Clinical Investigation 117 (12):4034-43.

Cano, D.A., Rulifson, I.C., Heiser, P.W., Swigart, L.B., Pelengaris, German, M.S., Evan, G. I., Bluestone, J.A., and M. Hebrok (2008): Regulated ß-cell regeneration in the adult mouse pancreas, Diabetes 7 (4): 958-966, Dec 14. 2007; [Epub ahead of print].

Bluestone, J.A. and M. Hebrok (2008): Safer, longer-lasting regulatory T cells with stable ß-catenin. Nature Medicine 14(2):118-119.

Heiser, P. W., Cano, D. A., Kim, G. E., Kench, J. G., Klimstra, D. S., Taketo, M., Biankin, A. V., and M. Hebrok (2008): Stabilization of ß-catenin induces pancreas tumor formation. Gastroenterology 2008 Jul 9. [Epub ahead of print].

Cano, D. A., and M. Hebrok (2008): Hedgehog spikes pancreas regeneration, Gastroenterology 135, 347-351.

Cervantes, S., Yamaguchi, T. and M. Hebrok (2008): Wnt5a is essential for intestinal elongation in mice. Developmental Biology, in press.

Puri, S., Cano, D. A., and M. Hebrok (2008): A role for Von-Hippel Lindau Protein in Pancreatic ß-cell function. Diabetes, [Epub ahead of print].

Nolan-Stevaux, O., Lau, J., Truitt, M. L., Chu, G. C., Hebrok, M., Fernandez-Zapico, M. and D. Hanahan (2008): GLI1 is regulated through Smoothened-independent mechanisms in neoplastic pancreatic ducts and mediates PDAC cell survival and transformation. Genes & Development, in press.

Wei, G., Yeh, R.-F., Hebrok, M, and M. Ramalho-Santos (2008): Extensive transcriptional similarities between embryonic stem cells and germ cells. submitted.

Sekine, S., Ogawa, R., Ito, R., Hiraoka, N., McManus, M.T., Kanai, Y., and M. Hebrok (2008): Hepatocyte-specific disruption of Dicer1 induces dysregulated oncofetal gene expression and promotes hepatocarcinogenesis. in revision.

Kockel, L., Kerr, K., Melnick, M., Hebrok, M. and N. Perrimon (2008): Dynamic switch of negative feedback regulation in Drosophila Akt-Tor signaling. in revision.

Pasca di Magliano, M., Morris, J. P., Wang, S. C., Heiser, P. W., Kim, G. E., Dlugosz, A. A., and Hebrok, M. (2008) Sporadic Epithelial Gli Activity Synergizes with Kras Activation in Promoting Pancreatic Adenocarcinoma in Mouse, submitted.

information last updated August 2009