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Natalia B Ivanova |
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| Assistant Professor |
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* Assistant Professor
* M.S. Moscow Institute for Physics and Technology, Moscow (Russia) 1991
* Ph.D. Engelhardt Institute for Molecular Biology, Moscow (Russia) 1996
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| Honors: | |
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| Robert T. McCluskey, M.D., Yale Scholar Award, 2007
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| Research Interests: | |
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* Molecular control of cell fate decisions in embryonic and somatic stem cells
* Lineage specification during early mouse development
* Functional genomics
* Systems biology
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| Current Research: | |
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| Embryonic and adult stem cells hold great promise for regenerative medicine,
tissue repair and gene therapy. Embryonic stem cells represent a
transient cell population that exist during embryonic development and
can give rise to all cell types present in an adult, while adult
(somatic) stem cells are permanent cell populations dedicated to
homeostatic production of mature cells in tissues such as blood, skin
and gut. All stem cells must be able to balance self-renewal versus
differentiation, regulate proliferation and cell death.
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| Our long-term goal is to understand how cell-fate decisions in stem cells
are regulated at the molecular level. We employ a broad-based
strategy that integrates molecular, cellular and organismal
approaches. Our research efforts are divided between the two stem
cell systems:
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| Embryonic stem cells: | |
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| We have recently developed a functional genomics approach to
identify genetic mechanisms that control self-renewal in embryonic
stem cells. This approach utilizes short hairpin RNA (shRNA)
loss-of-function techniques to downregulate a set of gene products
whose expression patterns suggest self-renewal regulatory functions.
We have applied this approach to a selected panel of candidate
regulators and demonstrated that in addition to
previously identified Nanog, Oct4 and Sox2 several
other genes are required for efficient self-renewal of ES cells in
vitro (Ivanova et al., Nature 2006).
We are currently extending this screening strategy to genome-scale
shRNA libraries.
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| The ongoing projects include: 1) Large-scale loss-of-function analyses to
identify gene products that are required for self-renewal of mouse
and human ES cells, and for commitment to specific lineages, 2)
In-depth characterization of previously identified regulators of
self-renewal and differentiation, 3) Computational modeling of
lineage commitment.
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| Hematopoietic stem cells: | |
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| Hematopoiesis is organized as a hierarchy of cells of with decreasing self-renewal
and differentiation potential. Long-term HSC, the most primitive cell
in this hierarchy, can give rise to all blood lineages and has
unlimited capacity to self-renew. LT-HSC produces short-term HSC
which are still multipotent but are limited in self-renewal capacity.
ST-HSC differentiates further into lineage-committed progenitor
cells which are responsible for the large-scale production of mature
blood cells. We have chosen global gene expression analysis in
primary cells followed by functional characterization of candidate
gene products as an approach towards the comprehensive identification
of HSC regulatory mechanisms.
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| To date we have performed transcriptional profiling of fetal and adult
HSC using microarray-based technologies and have defined sets of
genes that are specifically expressed in HSC but not in more
differentiated compartments of the hematopoietic hierarchy. Some of
these candidate genes are likely to function as key regulators of
self-renewal and differentiation (Ivanova, Science 2002). We
are currently focusing on two projects: 1) Single-cell gene
expression analysis to define functional subsets within HSC and 2)
Functional analyses of candidate genes to identify gene-products that
are necessary and/or sufficient for self-renewal of HSC both in
vivo and in vitro.
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| Representative Publications: | |
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Fasano
C, Dimos J, Ivanova N, Lowry N, Lemischka I, Temple S.
shRNA Knockdown of Bmi-1 Reveals a Critical Role for p21-Rb Pathway
in NSC Self-Renewal during Development. Cell Stem Cell 2007 1:
87-99.
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Dimos J, Schaniel C, Hackney J, Moore K, Ramalho-Santos M, Yoon S,
Matsuzaki Y, Mulligan R, Melton D, and Lemischka
I. Response to Comments on " 'Stemness': Transcriptional
Profiling of Embryonic and Adult Stem Cells" and "A Stem
Cell Molecular Signature". Science 2003: 393.
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| Ivanova
N, Dimos J, Schaniel C, Hackney J, Moore K, Lemischka I. A
Stem Cell Molecular Signature. Science 2002 298: 601-604
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Haan G, Bystrykh L, Weersing E, Dontje B, Geiger H, Ivanova N,
Lemischka I, Vellenga E, Van Zant G. A genetic and genomic analysis
identifies a cluster of genes associated with hematopoietic turnover.
Blood 2002, 100(6): 2056-2062
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| Phillips
R, Ernst R, Brunk B, Ivanova N, Moore K, Overton G and
Lemischka I. The Genetic Program of Hematopoietic Stem Cells.
Science. 2000 Jun 2;288(5471):1635-40.
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| Ivanova
N, Luchinskaya N, Popsueva A and Belyavsky A. Identification
of mRNAs localized in different regions of Xenopus laevis embryos at
the early gastrula stage. Dokl. Akad. Nauk (Russian) 1998,
359, n. 1, p. 156-162.
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| Ivanova
N and Belyavsky A. Restriction endonuclease-based gene
expression fingerprinting: basic technique and modifications. In
Current Innovations in Molecular Biology: Gene Cloning and Analysis.
Ed. B. Schaefer. Horizon Scientific Press, Wymondham, UK, 1997,
p.43-60 (book chapter).
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| Ivanova
N and Belyavsky A. Identification of differentially expressed
genes by restriction endonuclease-based gene expression
fingerprinting., Nucleic Acids Res. 1995, v. 23, p.
2954-2958.
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| Contact Information: | | |
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