Rebecca A. Ihrie, Ph.D.

Associate Professor

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Faculty Appointments
Associate Professor of Cell & Developmental Biology Associate Professor of Neurological Surgery
Ph.D., Cancer Biology, Stanford University, Stanford, CaliforniaB.S., Biochemistry, University of Michigan, Ann Arbor, Michigan
Office Address
MCN B2317
1161 21st Ave
Nashville, TN 37232-6840
Research Description
I am interested in the signaling pathways regulating proliferation and differentiation in neural stem/progenitor cells and brain tumor cells. My long-term goals are to reveal how the normal proliferation and differentiation of stem cells is controlled in the brain, dissect how perturbations of these pathways results in neurological diseases, and leverage these findings to treat human disease. In my independent lab, I lead a group which includes a senior neurosurgery resident, practicing neuropathologist, and three graduate students. I work collaboratively with neurosurgeons, neurologists, developmental biologists, and cancer systems biology faculty to map cell-to-cell differences in proliferative signaling in neural stem cells, neurodevelopmental disorders, and all grades of brain tumors.

My laboratory uses cytometric approaches to 1) identify proliferative pathways that are differentially active within cell subsets in the stem cell niche of the ventricular-subventricular zone), 2) determine how this pattern of activation is altered in disease states, particularly pediatric neurological disorders and adult high-grade brain tumors, and 3) directly identify subpopulations of progenitor-like brain tumor cells using multiparameter single-cell protein analyses. @IhrieLab

Research Keywords
Stem Cells, Brain Tumors , Developmental Biology , Systems Biology , Signal Transduction , Computational and Systems Biology , Stem Cell Biology & Regeneration , Cancer Biology , Cell Signaling , Developmental Neuroscience , Developmental Biology, Flow cytometry, Mass cytometry, Imaging
Ajaib S, Lodha D, Pollock S, Hemmings G, Finetti MA, Gusnanto A, Chakrabarty A, Ismail A, Wilson E, Varn FS, Hunter B, Filby A, Brockman AA, McDonald D, Verhaak RGW, Ihrie RA, Stead LF. GBMdeconvoluteR accurately infers proportions of neoplastic and immune cell populations from bulk glioblastoma transcriptomics data. Neuro Oncol. 2023 Jul 7/6/2023; 25(7): 1236-48. PMID: 36689332, PMCID: PMC10326489, PII: 6998507, DOI: 10.1093/neuonc/noad021, ISSN: 1523-5866.

Bartkowiak T, Lima SM, Hayes MJ, Mistry AM, Brockman AA, Sinnaeve J, Leelatian N, Roe CE, Mobley BC, Chotai S, Weaver KD, Thompson RC, Chambless LB, Ihrie RA, Irish JM. An immunosuppressed microenvironment distinguishes lateral ventricle-contacting glioblastomas. JCI Insight. 2023 Jun 6/22/2023; 8(12): PMID: 37192001, PMCID: PMC10371245, PII: 160652, DOI: 10.1172/jci.insight.160652, ISSN: 2379-3708.

Brockman AA, Khurana R, Bartkowiak T, Thomas PL, Sivagnanam S, Betts CB, Coussens LM, Lovly CM, Irish JM, Ihrie RA. Alignment, segmentation and neighborhood analysis in cyclic immunohistochemistry data using CASSATT. Cytometry B Clin Cytom [print-electronic]. 2023 Feb 2/7/2023; PMID: 36748312, DOI: 10.1002/cyto.b.22114, ISSN: 1552-4957.

Medina S, Ihrie RA, Irish JM. Learning cell identity in immunology, neuroscience, and cancer. Semin Immunopathol [print-electronic]. 2023 Jan; 45(1): 3-16. PMID: 36534139, PMCID: PMC9762661, PII: 10.1007/s00281-022-00976-y, DOI: 10.1007/s00281-022-00976-y, ISSN: 1863-2300.

Ihrie RA, Henske EP. Modeling tuberous sclerosis with organoids. Science [print-electronic]. 2022 Jan 1/28/2022; 375(6579): 382-3. PMID: 35084978, DOI: 10.1126/science.abn6158, ISSN: 1095-9203.

Embalabala RJ, Brockman AA, Jurewicz AR, Kong JA, Ryan K, Guinto CD, Álvarez-Buylla A, Chiang C, Ihrie RA. GLI3 Is Required for OLIG2+ Progeny Production in Adult Dorsal Neural Stem Cells. Cells. 2022 Jan 1/10/2022; 11(2): PMID: 35053334, PMCID: PMC8773499, PII: cells11020218, DOI: 10.3390/cells11020218, ISSN: 2073-4409.

Brockman AA, Mobley BC, Ihrie RA. Histological Studies of the Ventricular-Subventricular Zone as Neural Stem Cell and Glioma Stem Cell Niche. J Histochem Cytochem [print-electronic]. 2021 Dec; 69(12): 819-34. PMID: 34310246, PMCID: PMC8647632, DOI: 10.1369/00221554211032003, ISSN: 1551-5044.

Chervonski E, Brockman AA, Khurana R, Chen Y, Greenberg S, Hay MS, Luo Y, Miller J, Patelis D, Whitney SK, Walker M, Ihrie RA. Creation and validation of 3D-printed head molds for stereotaxic injections of neonatal mouse brains. J Neurosci Methods [print-electronic]. 2021 Aug 8/1/2021; 360: 109255. PMID: 34139267, PMCID: PMC8324552, PII: S0165-0270(21)00190-4, DOI: 10.1016/j.jneumeth.2021.109255, ISSN: 1872-678X.

Geben LC, Mobley BC, Brockman AA, Pastakia D, Naftel R, Ihrie RA, Esbenshade AJ. Sustained response to erlotinib and rapamycin in a patient with pediatric anaplastic oligodendroglioma. Pediatr Blood Cancer [print-electronic]. 2021 Jan; 68(1): e28750. PMID: 33001573, PMCID: PMC9153653, DOI: 10.1002/pbc.28750, ISSN: 1545-5017.

Klofas LK, Short BP, Snow JP, Sinnaeve J, Rushing GV, Westlake G, Weinstein W, Ihrie RA, Ess KC, Carson RP. DEPDC5 haploinsufficiency drives increased mTORC1 signaling and abnormal morphology in human iPSC-derived cortical neurons. Neurobiol Dis [print-electronic]. 2020 Sep; 143: 104975. PMID: 32574724, PMCID: PMC7462127, PII: S0969-9961(20)30250-3, DOI: 10.1016/j.nbd.2020.104975, ISSN: 1095-953X.

Leelatian N, Sinnaeve J, Mistry AM, Barone SM, Brockman AA, Diggins KE, Greenplate AR, Weaver KD, Thompson RC, Chambless LB, Mobley BC, Ihrie RA, Irish JM. Unsupervised machine learning reveals risk stratifying glioblastoma tumor cells. Elife. 2020 Jun 6/23/2020; 9: PMID: 32573435, PMCID: PMC7340505, PII: 56879, DOI: 10.7554/eLife.56879, ISSN: 2050-084X.

Mistry AM, Mummareddy N, Salwi S, Davis LT, Ihrie RA. Glioblastoma Distance From the Subventricular Neural Stem Cell Niche Does Not Correlate With Survival. Front Oncol. 2020; 10: 564889. PMID: 33363006, PMCID: PMC7759619, DOI: 10.3389/fonc.2020.564889, ISSN: 2234-943X.

Cameron BD, Traver G, Roland JT, Brockman AA, Dean D, Johnson L, Boyd K, Ihrie RA, Freeman ML. Bcl2-expressing quiescent type B neural stem cells in the V-SVZ are resistant to concurrent temozolomide/X-irradiation. Stem Cells [print-electronic]. 2019 Aug 8/20/2019; PMID: 31430423, DOI: 10.1002/stem.3081, ISSN: 1549-4918.

Mistry AM, Greenplate AR, Ihrie RA, Irish JM. Beyond the message: advantages of snapshot proteomics with single-cell mass cytometry in solid tumors. FEBS J [print-electronic]. 2019 Apr; 286(8): 1523-39. PMID: 30549207, PMCID: PMC6478512, DOI: 10.1111/febs.14730, ISSN: 1742-4658.

Rushing GV, Brockman AA, Bollig MK, Leelatian N, Mobley BC, Irish JM, Ess KC, Fu C, Ihrie RA. Location-dependent maintenance of intrinsic susceptibility to mTORC1-driven tumorigenesis. Life Sci Alliance [electronic-print]. 2019 Apr; 2(2): PMID: 30910807, PMCID: PMC6435042, PII: 2/2/e201800218, DOI: 10.26508/lsa.201800218, ISSN: 2575-1077.

Mistry AM, Wooten DJ, Davis LT, Mobley BC, Quaranta V, Ihrie RA. Ventricular-Subventricular Zone Contact by Glioblastoma is Not Associated with Molecular Signatures in Bulk Tumor Data. Sci Rep. 2019 Feb 2/12/2019; 9(1): 1842. PMID: 30755636, PMCID: PMC6372607, PII: 10.1038/s41598-018-37734-w, DOI: 10.1038/s41598-018-37734-w, ISSN: 2045-2322.

Rushing GV, Bollig MK, Ihrie RA. Heterogeneity of Neural Stem Cells in the Ventricular-Subventricular Zone. Adv. Exp. Med. Biol. 2019; 1169: 1-30. PMID: 31487016, DOI: 10.1007/978-3-030-24108-7_1, ISSN: 0065-2598.

Garcia ADR, Han YG, Triplett JW, Farmer WT, Harwell CC, Ihrie RA. The Elegance of Sonic Hedgehog: Emerging Novel Functions for a Classic Morphogen. J. Neurosci. 2018 Oct 10/31/2018; 38(44): 9338-45. PMID: 30381425, PMCID: PMC6209836, PII: 38/44/9338, DOI: 10.1523/JNEUROSCI.1662-18.2018, ISSN: 1529-2401.

Sinnaeve J, Mobley BC, Ihrie RA. Space Invaders: Brain Tumor Exploitation of the Stem Cell Niche. Am. J. Pathol [print-electronic]. 2018 Jan; 188(1): 29-38. PMID: 29024634, PMCID: PMC5745521, PII: S0002-9440(17)30315-2, DOI: 10.1016/j.ajpath.2017.08.029, ISSN: 1525-2191.

Sinnaeve J, Mobley BC, Ihrie RA. Space Invaders: Brain Tumor Exploitation of the Stem Cell Niche. Am. J. Pathol [print-electronic]. 2018 Jan; 188(1): 29-38. PMID: 29024634, PMCID: PMC5745521, PII: S0002-9440(17)30315-2, DOI: 10.1016/j.ajpath.2017.08.029, ISSN: 1525-2191.

Yang YP, Ma H, Starchenko A, Huh WJ, Li W, Hickman FE, Zhang Q, Franklin JL, Mortlock DP, Fuhrmann S, Carter BD, Ihrie RA, Coffey RJ. A Chimeric Egfr Protein Reporter Mouse Reveals Egfr Localization and Trafficking In Vivo. Cell Rep. 2017 May 5/9/2017; 19(6): 1257-67. PMID: 28494873, PII: S2211-1247(17)30542-9, DOI: 10.1016/j.celrep.2017.04.048, ISSN: 2211-1247.

Leelatian N, Doxie DB, Greenplate AR, Sinnaeve J, Ihrie RA, Irish JM. Preparing Viable Single Cells from Human Tissue and Tumors for Cytomic Analysis. Curr Protoc Mol Biol. 2017 Apr 4/3/2017; 118: 25C.1.1-25C.1.23. PMID: 28369679, DOI: 10.1002/cpmb.37, ISSN: 1934-3647.

Mistry AM, Dewan MC, White-Dzuro GA, Brinson PR, Weaver KD, Thompson RC, Ihrie RA, Chambless LB. Decreased survival in glioblastomas is specific to contact with the ventricular-subventricular zone, not subgranular zone or corpus callosum. J. Neurooncol [print-electronic]. 2017 Apr; 132(2): 341-9. PMID: 28074322, PII: 10.1007/s11060-017-2374-3, DOI: 10.1007/s11060-017-2374-3, ISSN: 1573-7373.

Mistry AM, Hale AT, Chambless LB, Weaver KD, Thompson RC, Ihrie RA. Influence of glioblastoma contact with the lateral ventricle on survival: a meta-analysis. J. Neurooncol [print-electronic]. 2017 Jan; 131(1): 125-33. PMID: 27644688, PMCID: PMC5262526, PII: 10.1007/s11060-016-2278-7, DOI: 10.1007/s11060-016-2278-7, ISSN: 1573-7373.

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. Single cell analysis of human tissues and solid tumors with mass cytometry. Cytometry B Clin Cytom [print-electronic]. 2017 Jan; 92(1): 68-78. PMID: 27598832, PMCID: PMC5459378, DOI: 10.1002/cyto.b.21481, ISSN: 1552-4957.

Rushing G, Ihrie RA. Neural stem cell heterogeneity through time and space in the ventricular-subventricular zone. Front Biol (Beijing) [print-electronic]. 2016 Aug; 11(4): 261-84. PMID: 28367160, PMCID: PMC5371406, DOI: 10.1007/s11515-016-1407-1, ISSN: 1674-7984.

Leelatian N, Ihrie RA. Head of the Class: OLIG2 and Glioblastoma Phenotype. Cancer Cell. 2016 May 5/9/2016; 29(5): 613-5. PMID: 27165737, PII: S1535-6108(16)30165-9, DOI: 10.1016/j.ccell.2016.04.007, ISSN: 1878-3686.

Chong KM, Leelatian N, Deguire SM, Brockman AA, Earl D, Ihrie RA, Irish JM, Bachmann BO, Sulikowski GA. The use of fluorescently-tagged apoptolidins in cellular uptake and response studies. J. Antibiot [print-electronic]. 2016 Apr; 69(4): 327-30. PMID: 26956792, PII: ja201622, DOI: 10.1038/ja.2016.22, ISSN: 0021-8820.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.