Rebecca A Ihrie, Ph.D.
Assistant Professor of Cancer Biology
Professor of Neurological Surgery
761B Preston Research Building
2220 Pierce Avenue
Nashville, TN 37232
We study the biology of brain tumors and the properties of stem cells in normal brain.
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.
- 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, 109(22), 8710-5, 2012.
- 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, 478(7369), 382-6, 2011.
- Ihrie, RA, Alvarez-Buylla, A Lake-front property: a unique germinal niche by the lateral ventricles of the adult brain. Neuron, 70(4), 674-86, 2011.
- 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, 71(2), 250-62, 2011.
- 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, 2010759731, 2010.
- Ihrie, RA, Alvarez-Buylla, A Cells in the astroglial lineage are neural stem cells. Cell Tissue Res, 331(1), 179-91, 2008.
- 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. Cell Death Differ, 13(9), 1614-8, 2006.
- 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, 126(1), 69-73, 2006.
- Ihrie, RA, Attardi, LD A new Perp in the lineup: linking p63 and desmosomal adhesion. Cell Cycle, 4(7), 873-6, 2005.
- 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, 65(15), 6551-6, 2005.
- 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, 120(6), 843-56, 2005.
- 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, 2(11), e332, 2004.
- Ihrie, RA, Attardi, LD Perp-etrating p53-dependent apoptosis. Cell Cycle, 3(3), 267-9, 2004.
- 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, 13(22), 1985-90, 2003.