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Vanderbilt-Ingram Cancer CenterVanderbilt-Ingram Cancer Center

 
Rebecca A Ihrie

Rebecca A Ihrie, Ph.D.

Assistant Professor of Cancer Biology
Assistant Professor of Neurological Surgery

Contact Information:

761B Preston Research Building
2220 Pierce Avenue
Nashville, TN 37232
615-936-2951
Fax: 615-936-2911

Profile

My research laboratory is focused on understanding how cells in the healthy and diseased brain control their proliferation and their ability to make the different cell types of the brain. We work with basic researchers, medical researchers, and neurosurgeons to study stem cells in the normal brain and stem-like cells in multiple brain tumor types.

Education
 
  • B.S. Honors Biochemistry, University of Michigan
  • Ph.D. Cancer Biology, Stanford University
  • Postdoctoral Fellow, UC - San Francisco
 
Research Description

My research background is in cancer biology, neurobiology, and stem cell biology. I am interested in how extracellular signals are integrated within stem cells to direct self-renewal, proliferation, and the generation of committed progeny. Rapidly dividing progenitor cells share many molecular features with cancer cells, and the pathways regulating neural stem cells are frequently disrupted or altered in tumorigenesis. My laboratory focuses on a germinal niche in the brain: the subventricular zone (SVZ). In the mouse, this region generates thousands of young neurons every week - a remarkable process in a largely quiescent tissue. Understanding how long-lived neural stem cells survive, proliferate and differentiate will provide insight into the etiology and treatment of brain tumors.

My lab combines in vitro and in vivo approaches to address two major questions in the field: How are the many extracellular signals acting on neural progenitors integrated to maintain the adult germinal zone? What are the consequences of disrupting these signaling pathways in specific neural progenitor populations? In addition to their functions in normal homeostasis, mutations in proliferative pathways - in particular, the growth factors PDGF and EGF and the downstream effector BRaf - are common in pediatric and adult forebrain tumors. Ectopic stimulation of these pathways in murine neural progenitors results in hyperplastic growth and invasion into surrounding tissue, suggesting that aberrant signaling in progenitors may be the initiating event(s) in gliomas. Research in my laboratory focuses on the fundamental biology of neural stem cells and progenitor-like tumor cells: how signals from the niche environment combine to affect self-renewal, neurogenesis, and identity, and how mutations in these signaling pathways affect the survival, invasion, and proliferation of tumor cells.

Publications
  • Tong CK, Fuentealba LC, Shah JK, Lindquist RA, Ihrie RA, Guinto CD, Rodas-Rodriguez JL, Alvarez-Buylla A. A Dorsal SHH-Dependent Domain in the V-SVZ Produces Large Numbers of Oligodendroglial Lineage Cells in the Postnatal Brain. Stem Cell Reports [print-electronic]. 2015 Oct 10/13/2015; 5(4): 461-70. PMID: 26411905, PMCID: PMC4624995, PII: S2213-6711(15)00247-7, DOI: 10.1016/j.stemcr.2015.08.013, ISSN: 2213-6711.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/26411905.
  • Shi SQ, Bichell TJ, Ihrie RA, Johnson CH. Ube3a imprinting impairs circadian robustness in Angelman syndrome models. Curr. Biol [print-electronic]. 2015 Mar 3/2/2015; 25(5): 537-45. PMID: 25660546, PMCID: PMC4348236, PII: S0960-9822(14)01650-9, DOI: 10.1016/j.cub.2014.12.047, ISSN: 1879-0445.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/25660546.
  • Chiang C, Ihrie RA. Controlling COR competence: BCL-6 regulates neurogenesis and tumor suppression. Cancer Cell. 2014 Dec 12/8/2014; 26(6): 773-4. PMID: 25490438, PII: S1535-6108(14)00471-1, DOI: 10.1016/j.ccell.2014.11.020, ISSN: 1878-3686.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/25490438.
  • Álvarez-Buylla A, Ihrie RA. Sonic hedgehog signaling in the postnatal brain. Semin. Cell Dev. Biol [print-electronic]. 2014 Sep; 33: 105-11. PMID: 24862855, PMCID: PMC4130786, PII: S1084-9521(14)00145-1, DOI: 10.1016/j.semcdb.2014.05.008, ISSN: 1096-3634.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/24862855.
  • Haskins WE, Zablotsky BL, Foret MR, Ihrie RA, Alvarez-Buylla A, Eisenman RN, Berger MS, Lin CH. Molecular Characteristics in MRI-Classified Group 1 Glioblastoma Multiforme. Front Oncol. 2013; 3: 182. PMID: 23875172, PMCID: PMC3708153, DOI: 10.3389/fonc.2013.00182, ISSN: 2234-943X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/23875172.
  • Huillard E, Hashizume R, Phillips JJ, Griveau A, Ihrie RA, Aoki Y, Nicolaides T, Perry A, Waldman T, McMahon M, Weiss WA, Petritsch C, James CD, Rowitch DH. Cooperative interactions of BRAFV600E kinase and CDKN2A locus deficiency in pediatric malignant astrocytoma as a basis for rational therapy. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2012 May 5/29/2012; 109(22): 8710-5. PMID: 22586120, PMCID: PMC3365162, PII: 1117255109, DOI: 10.1073/pnas.1117255109, ISSN: 1091-6490.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/22586120.
  • Sanai N, Nguyen T, Ihrie RA, Mirzadeh Z, Tsai HH, Wong M, Gupta N, Berger MS, Huang E, Garcia-Verdugo JM, Rowitch DH, Alvarez-Buylla A. Corridors of migrating neurons in the human brain and their decline during infancy. Nature. 2011 Oct 10/20/2011; 478(7369): 382-6. PMID: 21964341, PMCID: PMC3197903, PII: nature10487, DOI: 10.1038/nature10487, ISSN: 1476-4687.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/21964341.
  • Ihrie RA, Shah JK, Harwell CC, Levine JH, Guinto CD, Lezameta M, Kriegstein AR, Alvarez-Buylla A. Persistent sonic hedgehog signaling in adult brain determines neural stem cell positional identity. Neuron. 2011 Jul 7/28/2011; 71(2): 250-62. PMID: 21791285, PMCID: PMC3346180, PII: S0896-6273(11)00404-1, DOI: 10.1016/j.neuron.2011.05.018, ISSN: 1097-4199.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/21791285.
  • Ihrie RA, Alvarez-Buylla A. Lake-front property: a unique germinal niche by the lateral ventricles of the adult brain. Neuron. 2011 May 5/26/2011; 70(4): 674-86. PMID: 21609824, PMCID: PMC3346178, PII: S0896-6273(11)00382-5, DOI: 10.1016/j.neuron.2011.05.004, ISSN: 1097-4199.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/21609824.
  • Jheon AH, Mostowfi P, Snead ML, Ihrie RA, Sone E, Pramparo T, Attardi LD, Klein OD. PERP regulates enamel formation via effects on cell-cell adhesion and gene expression. J. Cell. Sci [print-electronic]. 2011 Mar 3/1/2011; 124(Pt 5): 745-54. PMID: 21285247, PMCID: PMC3039019, PII: jcs.078071, DOI: 10.1242/jcs.078071, ISSN: 1477-9137.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/21285247.
  • Beaudry VG, Ihrie RA, Jacobs SB, Nguyen B, Pathak N, Park E, Attardi LD. Loss of the desmosomal component perp impairs wound healing in vivo. Dermatol Res Pract [print-electronic]. 2010; 2010: 759731. PMID: 20628490, PMCID: PMC2902749, DOI: 10.1155/2010/759731, ISSN: 1687-6113.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/20628490.
  • Ihrie RA, Alvarez-Buylla A. Cells in the astroglial lineage are neural stem cells. Cell Tissue Res [print-electronic]. 2008 Jan; 331(1): 179-91. PMID: 17786483, DOI: 10.1007/s00441-007-0461-z, ISSN: 1432-0878.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/17786483.
  • Ihrie RA, Bronson RT, Attardi LD. Adult mice lacking the p53/p63 target gene Perp are not predisposed to spontaneous tumorigenesis but display features of ectodermal dysplasia syndromes [letter]. Cell Death Differ [print-electronic]. 2006 Sep; 13(9): 1614-8. PMID: 16485031, PII: 4401871, DOI: 10.1038/sj.cdd.4401871, ISSN: 1350-9047.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/16485031.
  • Marques MR, Ihrie RA, Horner JS, Attardi LD. The requirement for perp in postnatal viability and epithelial integrity reflects an intrinsic role in stratified epithelia. J. Invest. Dermatol. 2006 Jan; 126(1): 69-73. PMID: 16417219, PMCID: PMC2879258, PII: 5700032, DOI: 10.1038/sj.jid.5700032, ISSN: 0022-202X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/16417219.
  • Marques MR, Horner JS, Ihrie RA, Bronson RT, Attardi LD. Mice lacking the p53/p63 target gene Perp are resistant to papilloma development. Cancer Res. 2005 Aug 8/1/2005; 65(15): 6551-6. PMID: 16061634, PII: 65/15/6551, DOI: 10.1158/0008-5472.CAN-05-0366, ISSN: 0008-5472.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/16061634.
  • Ihrie RA, Attardi LD. A new Perp in the lineup: linking p63 and desmosomal adhesion. Cell Cycle [print-electronic]. 2005 Jul; 4(7): 873-6. PMID: 15970683, PII: 1836, ISSN: 1551-4005.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15970683.
  • Ihrie RA, Marques MR, Nguyen BT, Horner JS, Papazoglu C, Bronson RT, Mills AA, Attardi LD. Perp is a p63-regulated gene essential for epithelial integrity. Cell. 2005 Mar 3/25/2005; 120(6): 843-56. PMID: 15797384, PII: S0092-8674(05)00046-2, DOI: 10.1016/j.cell.2005.01.008, ISSN: 0092-8674.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15797384.
  • Beer S, Zetterberg A, Ihrie RA, McTaggart RA, Yang Q, Bradon N, Arvanitis C, Attardi LD, Feng S, Ruebner B, Cardiff RD, Felsher DW. Developmental context determines latency of MYC-induced tumorigenesis. PLoS Biol [print-electronic]. 2004 Nov; 2(11): e332. PMID: 15455033, PMCID: PMC519000, DOI: 10.1371/journal.pbio.0020332, ISSN: 1545-7885.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15455033.
  • Ihrie RA, Attardi LD. Perp-etrating p53-dependent apoptosis. Cell Cycle [print-electronic]. 2004 Mar; 3(3): 267-9. PMID: 14726658, PII: 722, ISSN: 1538-4101.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/14726658.
  • Ihrie RA, Reczek E, Horner JS, Khachatrian L, Sage J, Jacks T, Attardi LD. Perp is a mediator of p53-dependent apoptosis in diverse cell types. Curr. Biol. 2003 Nov 11/11/2003; 13(22): 1985-90. PMID: 14614825, PII: S0960982203008236, ISSN: 0960-9822.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/14614825.