Ihor R. Lemischka
- DIRECTOR THE BLACK FAMILY STEM CELL INSTITUTE
- PROFESSOR Developmental and Regenerative Biology
- PROFESSOR Pharmacology and Systems Therapeutics
Ph.D., Massachusetts Institute of Technology
Whitehead Institute for Biomedical Research
Whitehead Institute for Biomedical Research
Massachusetts Institute of Technology
Massachusetts Institute of Technology
B.A., Johns Hopkins University
- 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.
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.
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.
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.
Moore ka, Lemischka ir. Stem cells and their niches. Science 2006; 311.
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.
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.
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.
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.
Ivanova nb, Dimos jt, Schaniel c, Hackney ja, Moore ka, Lemischka ir. A stem cell molecular signature. Science 2002; 298.
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.
Petrenko o, Beavis a, Klaine m, Godin i, Lemischka ir. The molecular characterization of the fetal stem cell marker AA4. Immunity 1999; 10.
Schaniel C, Ang YS, Ratnakumar K, Cormier C, James T, Bernstein E, Lemischka IR, Paddison PJ. Smarcc1/Baf155 couples self-renewal gene repression with changes in chromatin structure in mouse embryonic stem cells. Stem cells (Dayton, Ohio) 2009 Dec; 27(12).
Macarthur BD, Ma'ayan A, Lemischka IR. Systems biology of stem cell fate and cellular reprogramming. Nature reviews. Molecular cell biology 2009 Oct; 10(10).
Tarleton HP, Lemischka IR. Delayed differentiation in embryonic stem cells and mesodermal progenitors in the absence of CtBP2. Mechanisms of development; 127(1-2).
MacArthur BD, Ma'ayan A, Lemischka IR. Toward stem cell systems biology: from molecules to networks and landscapes. Cold Spring Harbor symposia on quantitative biology 2008; 73.
MacArthur BD, Lachmann A, Lemischka IR, Ma'ayan A. GATE: software for the analysis and visualization of high-dimensional time series expression data. Bioinformatics (Oxford, England) 2010 Jan; 26(1).
Xu H, Lemischka IR, Ma'ayan A. SVM classifier to predict genes important for self-renewal and pluripotency of mouse embryonic stem cells. BMC systems biology 2010; 4.
Xu H, Schaniel C, Lemischka IR, Ma'ayan A. Toward a complete in silico, multi-layered embryonic stem cell regulatory network. Wiley interdisciplinary reviews. Systems biology and medicine; 2(6).
Schaniel C, Lee DF, Lemischka IR. Exploration of self-renewal and pluripotency in ES cells using RNAi. Methods in enzymology 2010; 477.
Carvajal-Vergara X, Sevilla A, D'Souza SL, Ang YS, Schaniel C, Lee DF, Yang L, Kaplan AD, Adler ED, Rozov R, Ge Y, Cohen N, Edelmann LJ, Chang B, Waghray A, Su J, Pardo S, Lichtenbelt KD, Tartaglia M, Gelb BD, Lemischka IR. Patient-specific induced pluripotent stem-cell-derived models of LEOPARD syndrome. Nature 2010 Jun; 465(7299).
Lemischka IR. Hooking up with Oct4. Cell stem cell 2010 Apr 6(4).
Lu R, Markowetz F, Unwin RD, Leek JT, Airoldi EM, MacArthur BD, Lachmann A, Rozov R, Ma'ayan A, Boyer LA, Troyanskaya OG, Whetton AD, Lemischka IR. Systems-level dynamic analyses of fate change in murine embryonic stem cells. Nature 2009 Nov; 462(7271).
Ang YS, Tsai SY, Lee DF, Monk J, Su J, Ratnakumar K, Ding J, Ge Y, Darr H, Chang B, Wang J, Rendl M, Bernstein E, Schaniel C, Lemischka IR. Wdr5 Mediates Self-Renewal and Reprogramming via the Embryonic Stem Cell Core Transcriptional Network. Cell 2011 Apr;.
Josowitz R, Carvajal-Vergara X, Lemischka IR, Gelb BD. Induced pluripotent stem cell-derived cardiomyocytes as models for genetic cardiovascular disorders. Current opinion in cardiology 2011 May; 26(3).
Green MD, Chen A, Nostro MC, d'Souza SL, Schaniel C, Lemischka IR, Gouon-Evans V, Keller G, Snoeck HW. Generation of anterior foregut endoderm from human embryonic and induced pluripotent stem cells. Nature biotechnology 2011 Mar; 29(3).
Aguilo F, Avagyan S, Labar AS, Sevilla A, Lee DF, Kumar P, Lemischka IR, Zhou BY, Snoeck HW. Prdm16 is a physiological regulator of hematopoietic stem cells. Blood 2011 Feb;.
Honda H, Takubo K, Oda H, Kosaki K, Tazaki T, Yamasaki N, Miyazaki K, Moore KA, Honda Z, Suda T, Lemischka IR. Hemp, an mbt domain-containing protein, plays essential roles in hematopoietic stem cell function and skeletal formation. Proceedings of the National Academy of Sciences of the United States of America 2011 Feb; 108(6).
Markowetz F, Mulder KW, Airoldi EM, Lemischka IR, Troyanskaya OG. Mapping dynamic histone acetylation patterns to gene expression in nanog-depleted murine embryonic stem cells. PLoS computational biology 2010; 6(12).
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Dr. Lemischka did not report having any of the following types of financial relationships with industry during 2012 and/or 2013: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
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