Profile

Visit the lab website at my.vanderbilt.edu/ihrielab

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 unique 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 stem cell maintenance, neurogenesis, and positional identity, and how mutations in these signaling pathways affect the survival, invasion, and proliferation of tumor cells. 

Publications

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. Preparing Viable Single Cells from Human Tissue and Tumors for Cytomic Analysis. Leelatian N, Doxie DB, Greenplate AR, Sinnaeve J, Ihrie RA, Irish JM (2017) Curr Protoc Mol Biol : 25C.1.1-25C.1.23
    › Primary publication · 28369679 (PubMed)
  2. Neural stem cell heterogeneity through time and space in the ventricular-subventricular zone. Rushing G, Ihrie RA (2016) Front Biol (Beijing) 11(4): 261-284
    › Primary publication · 28367160 (PubMed) · PMC5371406 (PubMed Central)
  3. Decreased survival in glioblastomas is specific to contact with the ventricular-subventricular zone, not subgranular zone or corpus callosum. Mistry AM, Dewan MC, White-Dzuro GA, Brinson PR, Weaver KD, Thompson RC, Ihrie RA, Chambless LB (2017) J Neurooncol
    › Primary publication · 28074322 (PubMed)
  4. Influence of glioblastoma contact with the lateral ventricle on survival: a meta-analysis. Mistry AM, Hale AT, Chambless LB, Weaver KD, Thompson RC, Ihrie RA (2017) J Neurooncol 131(1): 125-133
    › Primary publication · 27644688 (PubMed) · PMC5262526 (PubMed Central)
  5. Single cell analysis of human tissues and solid tumors with mass cytometry. Leelatian N, Doxie DB, Greenplate AR, Mobley BC, Lehman JM, Sinnaeve J, Kauffmann RM, Werkhaven JA, Mistry AM, Weaver KD, Thompson RC, Massion PP, Hooks MA, Kelley MC, Chambless LB, Ihrie RA, Irish JM (2016) Cytometry B Clin Cytom
    › Primary publication · 27598832 (PubMed)
  6. Head of the Class: OLIG2 and Glioblastoma Phenotype. Leelatian N, Ihrie RA (2016) Cancer Cell 29(5): 613-5
    › Primary publication · 27165737 (PubMed)
  7. A Dorsal SHH-Dependent Domain in the V-SVZ Produces Large Numbers of Oligodendroglial Lineage Cells in the Postnatal Brain. Tong CK, Fuentealba LC, Shah JK, Lindquist RA, Ihrie RA, Guinto CD, Rodas-Rodriguez JL, Alvarez-Buylla A (2015) Stem Cell Reports 5(4): 461-70
    › Primary publication · 26411905 (PubMed) · PMC4624995 (PubMed Central)
  8. Ube3a imprinting impairs circadian robustness in Angelman syndrome models. Shi SQ, Bichell TJ, Ihrie RA, Johnson CH (2015) Curr Biol 25(5): 537-45
    › Primary publication · 25660546 (PubMed) · PMC4348236 (PubMed Central)
  9. Controlling COR competence: BCL-6 regulates neurogenesis and tumor suppression. Chiang C, Ihrie RA (2014) Cancer Cell 26(6): 773-4
    › Primary publication · 25490438 (PubMed)
  10. Sonic hedgehog signaling in the postnatal brain. Álvarez-Buylla A, Ihrie RA (2014) Semin Cell Dev Biol : 105-11
    › Primary publication · 24862855 (PubMed) · PMC4130786 (PubMed Central)
  11. Cooperative interactions of BRAFV600E kinase and CDKN2A locus deficiency in pediatric malignant astrocytoma as a basis for rational therapy. 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 (2012) Proc Natl Acad Sci U S A 109(22): 8710-5
    › Primary publication · 22586120 (PubMed) · PMC3365162 (PubMed Central)
  12. Corridors of migrating neurons in the human brain and their decline during infancy. 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 (2011) Nature 478(7369): 382-6
    › Primary publication · 21964341 (PubMed) · PMC3197903 (PubMed Central)
  13. Persistent sonic hedgehog signaling in adult brain determines neural stem cell positional identity. Ihrie RA, Shah JK, Harwell CC, Levine JH, Guinto CD, Lezameta M, Kriegstein AR, Alvarez-Buylla A (2011) Neuron 71(2): 250-62
    › Primary publication · 21791285 (PubMed) · PMC3346180 (PubMed Central)
  14. Lake-front property: a unique germinal niche by the lateral ventricles of the adult brain. Ihrie RA, Alvarez-Buylla A (2011) Neuron 70(4): 674-86
    › Primary publication · 21609824 (PubMed) · PMC3346178 (PubMed Central)
  15. Perp is a p63-regulated gene essential for epithelial integrity. Ihrie RA, Marques MR, Nguyen BT, Horner JS, Papazoglu C, Bronson RT, Mills AA, Attardi LD (2005) Cell 120(6): 843-56
    › Primary publication · 15797384 (PubMed)
  16. Perp is a mediator of p53-dependent apoptosis in diverse cell types. Ihrie RA, Reczek E, Horner JS, Khachatrian L, Sage J, Jacks T, Attardi LD (2003) Curr Biol 13(22): 1985-90
    › Primary publication · 14614825 (PubMed)