Cell and Developmental Biology University of Michigan

Research

Embryonic signaling pathways in cancer and regeneration

We're interested in understanding the functions of embryonic signaling pathways, particularly the Hedgehog and Wnt pathways, in cancer and regeneration. Current projects are examining: 1) How alterations in the Hedgehog pathway contribute to cancer initiation, progression, and maintenance, 2) The functional significance of paracrine signaling in Hedgehog-driven tumors, 3) How Hedgehog signaling regulates growth and regeneration of hair follicles, 4) Whether Hedgehog signaling exerts its growth- and tumor-promoting effects on stem cells, their transit-amplifying progeny, or both cell populations, 5) How the Hedgehog pathway influences the Wnt pathway and other signaling pathways, and the functional significance of this crosstalk, and 6) Whether targeting the Hedgehog pathway, and/or interacting pathways, could provide a useful approach for the treatment of certain types of cancer.

Lab Members

• Marina Grachtchouk
  Research Investigator
• Monique Verhaegen
  Research Investigator
• Angelo Ayar
  Research Fellow
• Kevin Nash
  Research Fellow
• Alexandre Ermilov
  Research Lab Specialist
• Joanna Pero
  Research Lab Technician
• Li-Jyun Syu
  Research Lab Specialist
• Dawn Wilbert
  Research Lab Technician
• Scott Lim
  Undergradate Student
• Tracy Stromer
  Undergradate Student
• Jack Weick
  Undergradate Student

Publications

Representative Publications

• Yang SH, Andl T, Grachtchouk V, Wang A, Liu J, Syu LJ, Ferris J, Wang T, Glick AB, Millar SE, Dlugosz AA. Pathological responses to oncogenic Hedgehog signaling in skin are dependent on canonical Wnt/β-catenin signaling. Nat Genet  40:1130-35, 2008.
• Michael LE, Westerman BA, Ermilov AN, Wang A, Ferris J, Liu J, Blom M, Ellison DW, van Lohuizen M, Dlugosz AA.  Bmi1 is required for Hedgehog-pathway driven medulloblastoma expansion. Neoplasia 10:1343-1349, 2008.
• Liu F, Chu EY, Watt B, Zhang Y, Gallant NM, Andl T, Yang SH, Lu MM, Piccolo S, Schmidt-Ullrich R, Taketo MM, Morrisey EE, Atit R, Dlugosz AA, Millar SE. Wnt/beta-catenin signaling directs multiple stages of tooth morphogenesis. Dev Biol 313:210-24, 2008.
• Pasca di Magliano M, Sekine S, Ermilov A, Ferris J, Dlugosz AA, Hebrok M. Hedgehog/Ras interactions regulate early stages of pancreatic cancer. Genes Dev 20:3161-73, 2006.
• Grachtchouk M, Liu J, Wang A, Wei L, Bichakjian C, Garlick J, Paulino A, Giordano T, Dlugosz A.  Odontogenic keratocysts arise from quiescent epithelial rests and are associate with deregulated Hedgehog signaling in mice and humans. Am J Pathol 169:806-814, 2006.
• Hutchin ME, Kariapper MST, Grachtchouk M, Wang A, Wei, L, Cummings D, Liu J, Michael LE, Glick A, Dlugosz AA. Sustained Hedgehog signaling is required for basal cell carcinoma proliferation and survival: conditional skin tumorigenesis recapitulates the hair growth cycle. Genes Dev 19:214-223, 2005.
• Grachtchouk V, Grachtchouk M, Lowe L, Johnson TJ, Wei L, Wang A, de Sauvage F, and Dlugosz AA.  The magnitude of hedgehog signaling activity defines skin tumor phenotype.  EMBO J  22:2741-2751, 2003.
• Sheng H, Goich S, Wang A, Grachtchouk M, Lowe L, Mo R, Lin K, de Sauvage FJ, Sasaki H, Hui C-c, and Dlugosz AA.  Dissecting the oncogenic potential of Gli2 in skin: deletion of an NH₂-terminal fragment alters tumor phenotype.  Cancer Res 62:5308-5316, 2002.
• Grachtchouk M, Rong M, Sandy Y, Zhang X, Sasaki H, Hui C-c and Dlugosz AA.  Basal cell carcinomas in mice overexpressing Gli2 in skin.  Nature Genet 24:216-217, 2000.
• Chiang C, Swan RZ, Grachtchouk M, Bolinger M, Litingtung Y, Robertson E, Cooper MK, Gaffield W, Westphal H, Beachy PA, and Dlugosz AA.  Essential role for Sonic hedgehog during hair follicle morphogenesis.  Dev Biol 205:1-9, 1999.