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Ihor R. Lemischka

PROFESSOR  Gene and Cell Medicine
PROFESSOR  Developmental and Regenerative Biology

Overview

Gender Male
E-mail ihor.lemischka@mssm.edu
Education and Training B.A., Johns Hopkins University
  Ph.D., Massachusetts Institute of Technology
  Post-doctoral Research Associate, Massachusetts Institute of Technology
  Post-doctoral Associate , Whitehead Institute for Biomedical Research
  Post-doctoral Fellow , Massachusetts Institute of Technology
  Post-doctoral Fellow , Whitehead Institute for Biomedical Research

Lemischka:Moore Laboratory for Integrative Stem Cell Biology

Read No Stem Cell Left Behind, a commentary by Dr. Lemischka published in The New York Times.

Training

Education and Training B.A., Johns Hopkins University
  Ph.D., Massachusetts Institute of Technology
  Post-doctoral Research Associate, Massachusetts Institute of Technology
  Post-doctoral Associate , Whitehead Institute for Biomedical Research
  Post-doctoral Fellow , Massachusetts Institute of Technology
  Post-doctoral Fellow , Whitehead Institute for Biomedical Research

Research

Lemischka:Moore Laboratory for Integrative Stem Cell Biology

The focus of my research is to understand the molecular and cellular nature of the undifferentiated stem cell "states", and how such states are altered during a change in cell fate. The underlying rationale for our studies is that the complement of gene-products and their inter-relationships that exist in stem cells accounts for their remarkable abilities to balance self-renewal and differentiation decision processes. We study both adult and embryonic stem (ES) cells, primarily from the mouse, but also from the human. As a first step, we have comprehensively identified most, if not all gene-products that are expressed in highly purified hematopoietic stem cell (HSC). We performed similar analyses in mouse ES cells. Such molecular "signatures" provide parts-lists that are available to the stem cells. The challenge has been to functionally address the roles that these molecules play in mediating the biological properties of HSC and ES cells. Further, we would like to understand how these molecular components are "wired" into regulatory signaling and transcriptional networks. To explore these issues we have utilized a number of global gene-expression perturbation technologies, such as inhibitory short hairpin RNA (shRNA). We have successfully down regulated the expression levels of candidate regulatory molecules in both HSC and ES cells. A number of these play crucial regulatory roles in processes such as self-renewal, proliferation, and differentiation. We have further developed strategies that allow the analyses of cell-fate change dynamics at multiple biochemical and molecular levels in response to defined and precisely controlled changes in the expression levels of key regulatory molecules. These strategies have provided the first in-depth view of how a cell-fate decision actually occurs at the transcriptional, post-transcriptional, translational, and post-translational levels. An important aspect of our overall efforts is computational and quantitative analyses. We anticipate that our approach will yield a systems biology level description and understanding of stem cell decision processes. This in turn, will have profound implications in future efforts focused on applying basic stem cell research in translational as well as clinical contexts.

For more information, please visit the Lemischka:Moore Laboratory for Integrative Stem Cell Biology website.

Publications

Fasano C, Dimos JT, Ivanova NB, Lowry N, Lemischka IR, 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.


Ivanova N, Dobrin R, Lu R, Kotenko I, Levorse J, DeCoste C, Schafer X, Lun Y, Lemischka IR. Dissecting self-renewal in stem cells with RNA interference. Nature 2006; 442: 533-538.


Moore KA, Lemischka IR. Stem cells and their niches. Science 2006; 311: 1880-1885.


Schaniel C, Li F, Schafer X, Moore T, Lemischka I, Paddison P. Delivery of short hairpin RNAs-triggers of gene silencing into mouse embryonic stem cells. Nature Methods 2006; 3: 6946-6951.


Pritsker M, Ford N, Jenq H, Lemischka IR. Genome-wide gain-of-function genetic screen identifies functionally active genes in mouse embryonic stem cells. Proc. Natl, Acad Sci USA 2006; 103: 6946-6951.


Shen Q, Wang Y, Dimos JT, Fasano CA, Phoenix TN, Lemischka IR, Ivanova NB, Stifani S, Morrisey EE, Temple S. The timing of cortical neurogenesis is encoded within lineages of individual progenitor cells. Nat Neurosci. 2006; 9: 743-751.


Pritsker M, Doniger T, Kramer L, Westcot S, Lemischka IR, . Diversification of stem cell molecular repertoire by alternative splicing. Proc. Natl. Acad. Sci. USA 2005; 102: 14290-14295.


Ivanova NB, Dimos JT, Schaniel C, Hackney JA, Moore KA, Lemischka IR. A stem cell molecular signature. Science 2002; 298: 601-604.


Phillips RL, Ernst RE, Brunk B, Ivanova N, Mahan MA, Deanehan JK, Moore KA, Overton GC, Lemischka IR. The Genetic Program of Hematopoietic Stem Cells. Science 2000; 288: 1635-1640.


Petrenko O, Beavis A, Klaine M, Godin I, Lemischka IR. The molecular characterization of the fetal stem cell marker AA4. Immunity 1999; 10: 691-700.


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