M. Isabel Dominguez, PhD
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PI: M. Isabel Dominguez, PhD Title: Assistant Professor
Research interests: Wnt signaling in development and cancer Contact: |
Research Interests:
Wnt signaling is essential for organ development and maintenance and its deregulation is the cause of several human diseases. My 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. We have two areas of interest:
Microinjection of CK2/ leads to axis duplication.
1) Our first area of interest is to characterize the molecular mechanism leading to activation of β-catenin, the key intracellular Wnt component that is upregulated in many human tumors. Using Xenopus embryos and mammalian cell lines, we have been collaborating with Dr. David Seldin’s group to determine the molecular mechanism utilized by a kinase upregulated in human tumors, CK2, to activate β-catenin. We found that CK2 is important for the stabilization of β-catenin by decreasing β-catenin interaction with its negative regulator, axin. Our ongoing studies focus on further characterizing the role of CK2 in the regulation of β-catenin activation in vivo and in vitro. 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.
2) Our second area of interest is to characterize the cellular and molecular mechanisms regulated by Wnt/β-catenin signaling during morphogenesis. Wnt/β-catenin signaling is essential for proper morphogenesis and thus, embryonic survival. Our recent data show that CK2 regulates morphogenesis in mice and Xenopus embryos. Ongoing experiments will determine the cellular, molecular and signaling processes that CK2 regulates during morphogenesis in mice. In addition, since CK2 activity can be regulated by environmental factors that are postulated to contribute to congenital diseases, we are studying the possible role of transient CK2 modulation in mediating embryonic malformations in Xenopus embryos. Our long-term goal is to identify means of preventing or correcting defects in morphogenetic processes that lead to congenital defects.
 LEF-eGFP reporter mouse. A faithful Wnt/β-catenin reporter that demonstrates Wnt/β-catenin signaling in embryos. |
 CK2α (Csnk2a1) homozygous mutant mice die by embryonic day (E)11 and display defects in the heart, neural tube, pharyngeal arches, tailbud and somites. |
This work has been supported by the NIH, the American Heart Association, the American Cancer Society, the Karin Grunebaum Cancer Research Foundation and the Avon Foundation.
Other research web sites
http://www.bumc.bu.edu/medicine/dominguez
Open laboratory positions:
We are looking for a minority postdoc/student or a technician.
Selected Publications:
Dominguez I, Degano IR, Chea K, Toselli P, Seldin DC. CK2α is Essential for Embryonic Morphogenesis. Mol Cell Biochem. 2011 (in press).
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 I . Threonine 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 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 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 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 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
Isabel’s Research Group
Jordan Carr
Pragya Kalla, Undergraduate Fellow
Yoshua Seidner, Undergraduate Volunteer
Emily Silva, Research Assistant
Kasthuri Sivalogan, Undergraduate Volunteer
Jyotirmaie Suryadevara, Undergraduate Volunteer
Former lab members:
Kathleen Chea (Research Assistant)
Victoria Gau (BU master’s student)
Hao Wu (Ph.D. student). Current position: Resident in Pathology, BMC
Irene Roman, Ph.D (Postdoctoral fellow). Current position: Research Associate. IMIM/Hospital del Mar. Barcelona
Yijang Lin (BU undergraduate student).
Collaborators:
David C. Seldin M.D., Ph.D. (Section of Hematology/Oncology, BUSM)
Hao Wu, Ph.D. (Pathology Department, BUSM)
Antonio de las Morenas, M.D. (Pathology Department, BUSM)
Paul Toselli, M.D., Ph.D. (Biochemistry Department, BUSM)
Bill Pu, M.D. (Children’s Hospital, Boston)
Daniel L. Weeks, PhD (Iowa University)
Elisabeth Ehler, Ph.D. (King’s College, London)
Ronglih Liao, Ph.D. (Brigham & Women’s Hospital, Boston)
Darrel Kotton, M.D. (Pulmonary Center, BUSM)
Karen Symes, PhD (Biochemistry Department, BUMS)
Shalender Bhasin, MD (Section of Endocrinology, Diabetes, and Nutrition, BUSM)
Herbert Cohen, MD (Renal Section, BUSM)
Links:
Society for Developmental Biology
Xenopus Molecular Marker Resource
Congenital Heart Defects NIHLBI
Evans Center for Interdisciplinary Biomedical Research
Developmental Biology Research Group (DBRG)
