Isabel Dominguez

Dominguez_Isabel-2-5x3-5Assistant Professor

Education:

B.S., 1988, Universidad del Pais Vasco/Basque Country University, Bilbao, Spain

M.Sc., 1989, Biochemistry Department, Universidad del Pais Vasco/Basque Country University, Bilbao, Spain

Ph.D., 1994, Centro de Biologia Molecular/Molecular Biology Center. Universidad Autonoma de Madrid, Madrid, Spain

Postdoctoral Fellow, 1994-1996, Beth Israel Hospital & Department of Microbiology and Molecular Genetics, Harvard Medical School. Boston, USA. (Mentor: Sergei Sokol)

Postdoctoral Fellow and Research associate, 1996-2001, Dana Farber Cancer Institute & Department of Genetics, Harvard Medical School. Boston, USA. (Mentor: Jeremy B.A. Green)

General field of research:

Embryonic development, Wnt signaling, tumorigenesis

Affiliations other than medicine:

Department of Medicine, Section of Hematology/Oncology

Cancer Center

Women’s Health Interdisciplinary Research Center

Developmental Biology Research Group (DBRG)

Evans Center for Interdisciplinary Biomedical Research

BUMC Genome Science Institute

Center for Regenerative Medicine (CReM)

Molecular Medicine Graduate Program

Biomolecular Pharmacology Graduate Program

Contact information:

Office

650 Albany Street X438

Phone: (617) 414 1829

Laboratory

650 Albany Street X430

Phone: (617) 638 7560

Fax: (617) 638 7530

isdoming@bu.edu

Summary of Research Interest:

Our research interest is to understand the cascade of intracellular events that leads to the activation of Wnt signaling and the biological role of the Wnt pathway during organ development and maintenance. In particular we are characterizing the molecular mechanism leading to activation of β-catenin, the key intracellular Wnt component that is upregulated in many human tumors. We are also studying the cellular and molecular mechanisms regulated by Wnt/β-catenin signaling during heart morphogenesis in mice and Xenopus laevis embryos. As we acquire a better understanding of the molecular events leading to β-catenin activation, we will be able to develop novel and specific inhibitors for the treatment of cancers with upregulated nuclear β-catenin levels, and preventing or correcting defects in morphogenetic processes that lead to congenital heart defects.

Other research websites:

http://www.bumc.bu.edu/hematology/research-activities/m-isabel-dominguez-phd-2/

Research group information

Mirka Hlavacova, Research Assistant mihla125@googlemail.com

Kathleen Chea, Research Assistant kathleenchea@gmail.com

Irene Roman, Ph.D (Postdoctoral fellow from the Beatriu de Pinos, Catalonian Government, Spain)

Victoria Gau (BU undergraduate student)

Yijang Lin (BU undergraduate student)

Keywords:

Wnt signaling; CK2; beta-catenin; Heart Development; Xenopus laevis; Breast Cancer

Publications:

Currier, N., Chea K., Hlavacova, M., Sussman, D.J., Seldin, D.C. Dominguez, I.Dynamic expression of a LEF-EGFP Wnt reporter in mouse development and cancer. Genesis 2010 Mar; 48(3): 183-94.

Wu H, Symes K, Seldin DC, Dominguez IThreonine 393 of β-catenin regulates interaction with Axin. J. Cell. Biochem. 2009; Sep 1;108(1):52-63.

Dominguez I, Sonenshein, GE, Seldin DC. CK2 as a regulator of Wnt and NFκB signaling in embryonic development and cancer. Cell. Mol. Life Sci. 2009; Jun;66(11-12):1850-7.

Bryja V, Schambony A, Čajánek L, Dominguez I, Arenas E, Schulte G. β-arrestin and casein kinase 1/2 define distinct branches of non-canonical WNT signaling pathways. EMBO Rep. 2008; 9(12):1244-50

Chitalia VC, Foy RL, Bachschmid MM, Zeng L, Panchenko MV, Zhou MI, Bharti A, Seldin DC, Lecker SH,Dominguez I, Cohen HT. Jade-1 inhibits Wnt signaling by ubiquitinating beta-catenin and mediates Wnt pathway inhibition by pVHL, Nat Cell Biol. 2008; 10(10):1208-16

Seldin DC , Lou DY, Toselli P, Landesman-Bollag E, Dominguez IGene targeting of CK2 catalytic subunits. Mol Cell Biochem. 2008; 316 (1-2):141-7

Lou DY, Dominguez I, Toselli P, Landesman-Bollag E, O’Brien C, Seldin DC. The alpha catalytic subunit of protein kinase CK2 is required for normal embryonic development Mol. Cell Biol. 2008; 28(1):131-9

Currier N, Solomon SE, Demicco EG, Chang DL, Farago M, Ying H, Dominguez I, Sonenshein GE, Cardiff RD, Xiao ZX, Sherr DH, Seldin DC. Oncogenic signaling pathways activated in DMBA-induced mouse mammary tumorsToxicologic Pathology 2005; 33(6):726-37

Dominguez I , Mizuno J, Wu H, Imbrie GA, Symes K, Seldin DC. A role for CK2α/β in Xenopus early embryonic development, Mol Cell Biochem 2005; 274(1-2):125-31

Farago M, Dominguez I, Landesman-Bollag E, Xu X, Rosner A, Cardiff RD, Seldin DC. Kinase inactive GSK3β promotes Wnt signaling and mammary tumorigenesis. Cancer Research 2005; 65(13):5792-801

Seldin DC, Landesman-Bollag E, Farago M, Currier N, Lou D, Dominguez ICK2 as a positive regulator of Wnt signaling and tumorigenesis. Mol Cell Biochem. 2005; 274(1-2):63-7

Green JB, Dominguez I, Davidson LA. Self-organization of vertebrate mesoderm based on simple boundary conditions. Dev Dyn 2004; 231(3):576-81

Dominguez I , Mizuno J, Wu H, Song DH, Symes K, Seldin DC. Protein kinase CK2 is required for dorsal axis formation in Xenopus embryos. Dev Biol 2004; 274(1):110-24

Song DH, Dominguez I, Mizuno J, Kaut M, Mohr SC, Seldin DC. CK2 Phosphorylation of the armadillo repeat region of β-catenin potenciates Wnt signaling J Biol Chem 2003; 278(26):24018-25

Dominguez I, Green JB. Missing links in GSK3 regulation. Dev Biol 2001; 235(2):303-13

Dominguez I, Green JB. Dorsal downregulation of GSK3β by a non-Wnt-like mechanism is an early molecular consequence of cortical rotation in early Xenopus embryos. Development 2000; 127(4):861-8

Dominguez I, Itoh K, Sokol SY. Role of glycogen synthase kinase-3β as a negative regulator of dorsoventral axis formation in Xenopus embryos. Proc Natl Acad Sci USA 1995; 92(18):8498-502

Technologies available for sharing upon request:

Xenopus laevis bioassays; immunoblotting; immunohistochemistry; real-time PCR; in situ hybridization.