M. Isabel Dominguez, PhD
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PI: M. Isabel Dominguez, PhD
Title: Research Assistant Professor Research interests: Wnt signaling in development and cancer |
Research Summary:
Our laboratory is interested in the signaling pathways that control vertebrate embryonic development, particularly in the Wnt signaling pathway. We are focusing our studies on the function, regulation and mechanism of action of two components of the Wnt pathway: the serine-threonine kinases CK2 and GSK3b.
- Microinjection of CK2 leads to axis duplication.
To understand the role of these kinases in embryonic development, we utilize two model organisms: the frog Xenopus laevis and the mouse. In Xenopus laevis, we have implicated CK2 and GSK3b in regulating maternal dorsal fate determination. Currently, we aim to determine how these two kinases are regulated endogenously during early Xenopus laevis development. In the mouse, through the study of CK2a ablated embryos, we have implicated CK2 in regulating cellular differentiation and morphogenesis of the heart (in collaboration with the Seldin lab). We are pursuing biochemical, molecular and genetic approaches to determine the downstream targets of CK2 during heart development.
Abnormal ventricular trabeculation in CK2 null embryos (Courtesy of Dr. Toselli)
Concomitantly, we are using these two model organisms and cell culture to understand the mechanism of action of CK2 and GSK3b in Wnt signaling (in collaboration with the Seldin lab). Utilizing Xenopus embryos, we have shown that CK2 is sufficient and necessary for canonical Wnt signaling. Ongoing studies focus in determining the mechanism of regulation of Wnt signaling by CK2, and in the development and testing of novel CK2 inhibitors in vivo and in vitro.
Co-investigators:
Research Assistants:
Kathleen Chea
Mirka Hiavacova
Former lab members:
Julie Cha
Junko Mizuno
Kerwin Tang
Hao Wu
Collaborators:
Paul Toselli, MD, PhD (Biochemistry Department, BUSM)
Ronglih Liao, PhD (Brigham & Women’s Hospital, Boston)
Shalender Bhasin, MD (Section of Endocrinology, Diabetes, and Nutrition, BUSM)
Herb Cohen (Renal Section, BUSM)
Vitezslav Bryja (Masaryk University, Brno, Czech Republic)
Darrel Kotton (Pulmonary Center, BUSM)
Karen Symes(Biochemistry Department, BUMS)
Links:
Society for Developmental Biology
Xenopus Molecular Marker Resource
Publications:
Wu H, Symes K, Seldin DC, Dominguez I . Threonine 393 of β-catenin regulates interaction with Axin. J. Cell. Biochem. 2009 (in press)
Dominguez I, Sonenshein, GE, Seldin DC. CK2 as a regulator of Wnt and NFkB signaling in embryonic development and cancer. Cell Mol Life Sci 2009 (in press)
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 I. Gene 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 tumors Toxicologic Pathology 2005; 33(6):726-37
Dominguez I, Mizuno J, Wu H, Imbrie GA, Symes K, Seldin DC. A role for CK2a/b 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 GSK3b 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 I. CK2 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 b-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 GSK3b 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-3b as a negative regulator of dorsoventral axis formation in Xenopus embryos. Proc Natl Acad Sci USA 1995; 92(18):8498-502
