Raymond Habas
Assistant Professor

UMDNJ
Dept. Biochemistry - Room 629
Piscataway. NJ 08854
(732) 235-4543
FAX - 4783
habasra@umdnj.edu

Understanding the role of Wnt signaling during vertebrate development and cancer

Research Fields

  • Signal Transduction
  • Gene Expression
  • Cell Biology
  • Developmental Biology
  • Cancer

My laboratory is focused on understanding the role of Wnt signaling during embryogenesis and tumorigenesis.

Understanding the development of an organism from a fertilized egg into a multi-cellular organism with proper polarity including dorso-ventral. anterior-posterior and left-right symmetry remains a challenge for biologists. This embryological process is tightly regulated temporally and spatially and results from interplay between several signaling pathways. and one key signaling pathway required is the Wnt pathway. Wnt signaling has been demonstrated to regulate critical cell fate determination. proliferation. behavior. adhesion. migration and polarity during development. Wnt and its signaling components. in addition to playing a crucial role in embryogenesis have been implicated in tumorigenesis and play causative roles in human colon cancers.

We are dissecting the Wnt signaling pathway using a multidisciplinary approach drawing on techniques from molecular biology. biochemistry. cell biology and embryology. Our primary system is the Xenopus laevis (frog) and mammalian culture cells.

The Wnt signaling cascade has evolved as a complex series of independent signaling modules and to date comprises of three signaling modules; a canonical. a non-canonical and a Wnt/Ca2+ pathway. The canonical pathway regulates cell fate determination and primary axis formation through gene transcription. the non-canonical pathway regulates cell movements through modification of the actin cytoskeleton and the Wnt/Ca2+ pathway impacts both cell movements and cell fate determination.

We are focusing our studies to define the molecular basis of Wnt signaling by analyzing the role of Dishevelled (Dvl). a key component. We are further continuing studies to define the Wnt signal transduction mechanism by analyzing a number of novel factors that impact both canonical and non-canonical pathways. These studies will provide a clearer understanding of the mechanisms of Wnt signaling and remains pivotal to our understanding of the molecular nature of embryology and cancer formation.

Selected Publications

Komiya Y, Habas R. (2008) Wnt signal transduction pathways. Organogenesis. 4(2):68-75.

Liu W, Sato A, Khadka D, Bharti R, Diaz H, Runnels LW, Habas R. (2008) Mechanism of activation of the Formin protein Daam1. Proc Natl Acad Sci U S A. 105(1):210-5.

Semenov MV, Habas R, Macdonald BT, He X. (2007) SnapShot: Noncanonical Wnt signaling pathways. Cell. 131(7):1378.

Habas R, He X. (2007) Cell signaling: moving to a Wnt-Rap. Curr Biol. 17(12):R474-7.

Harada Y, Yokota C, Habas R, Slusarski DC, He X. (2007) Retinoic acid-inducible G protein-coupled receptors bind to frizzled receptors and may activate non-canonical Wnt signaling. Biochem Biophys Res Commun. 358(4):968-75.

Sato A, Khadka DK, Liu W, Bharti R, Runnels LW, Dawid IB, Habas R. (2006) Profilin is an effector for Daam1 in non-canonical Wnt signaling and is required for vertebrate gastrulation. Development. 133(21):4219-31.

Habas R. (2006) Canonical Wnt signaling: an unexpected new player. Dev Cell. 11(2):138-9.

Habas R. He X. (2006) Activation of Rho and Rac by Wnt/frizzled signaling. Methods Enzymol. 406:500-11.

Su LT. Agapito MA. Li M. Simonson WT. Huttenlocher A. Habas R. Yue L. Runnels LW. (2006) TRPM7 regulates cell adhesion by controlling the calcium-dependent protease calpain. J Biol Chem. 281(16):11260-70.

Chen C. Ware SM. Sato A. Houston-Hawkins DE. Habas R. Matzuk MM. Shen MM. Brown CW. (2006) The Vg1-related protein Gdf3 acts in a Nodal signaling pathway in the pre-gastrulation mouse embryo.
Development. 133(2):319-29.

Zeng X. Tamai K. Doble B. Li S. Huang H. Habas R. Okamura H. Woodgett J. He X. (2005) A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation. Nature. 438(7069):873-7.

Wallingford JB. Habas R. (2005) The developmental biology of Dishevelled: an enigmatic protein governing cell fate and cell polarity. Development. 132(20):4421-36.

Park TJ. Gray RS. Sato A. Habas R. Wallingford JB. (2005) Subcellular localization and signaling properties of dishevelled in developing vertebrate embryos. Curr Biol. 15(11):1039-44.

Habas R. Dawid IB. (2005) Dishevelled and Wnt signaling: is the nucleus the final frontier? J Biol. 4(1):2.

Nakaya MA. Habas R. Biris K. Dunty WC Jr. Kato Y. He X. Yamaguchi TP. (2004) Identification and comparative expression analyses of Daam genes in mouse and Xenopus. Gene Expr Patterns. 5(1):97-105.

Lee H. Habas R. Abate-Shen C. (2004) MSX1 cooperates with histone H1b for inhibition of transcription and myogenesis. Science. 304(5677):1675-8.

Tsang M. Maegawa S. Kiang A. Habas R. Weinberg E. Dawid IB. (2004) A role for MKP3 in axial patterning of the zebrafish embryo. Development. 131(12):2769-79.

Habas. R.. Dawid. I.B. and He. X. (2003). Co-activation of Rac and Rho by Wnt/frizzled signaling is required for Vertebrate gastrulation. Genes and Development 17:295-309.

Hukriede. N.A.. Tsang. T.E.. Habas. R.. Khoo. P.L.. Weeks. D.L.. Tam. P.P.L. and Dawid. I.B. (2003). Conserved requirement of Lim1 function for cell movements during gastrulation. Developmental Cell 4:83-94.

Kato. Y.. Habas. R.. Katsuyama. Y.. Naar. A. and He. X. (2002). A component of the mediator complex specific for Nodal/TGF- signaling. Nature 418: 641-646.

Capelluto. D.. Kutateladze. T.. * Habas. R.. * Finkielstein. C.. * He. X. and Overduin. M. (2002). DIX domain targets Dishevelled to actin stress fibers and membranes. Nature 419: 726-9. (* = equal contributors)

Habas. R.. Kato. Y. and He. X. (2001). Wnt/Frizzled activation of Rho regulates vertebrate gastrulation and requires a novel formin homology protein Daam1. Cell 107: 843-854.