Ty William Abel, Ph.D., M.D.

Associate Professor

Faculty Appointments
Associate Professor of Pathology, Microbiology and Immunology
M.D., Medicine, University of Arizona, Tucson, ArizonaPh.D., Neuroscience, University of Arizona, Tucson, ArizonaM.S., Neuroscience, University of Arizona, Tucson, ArizonaB.A., Psychology, Boise State University , Boise, Idaho
Office Address
C-2318 MCN
1161 21st Ave South
Nashville, TN 37232-2561
Research Description
Glioma is a type of brain cancer. The most common type of brain cancer in adults is a type of glioma known as glioblastoma multiforme (GBM). Better treatments for GBM are sorely needed; currently, the median survival for patients diagnosed with this type cancer is only about one year. As with all types of cancer, the more we know about the causes of the disease, the interactions among cancerous and non-cancerous cells, and the molecular pathways that promote disease progression, the greater the likelihood that novel, effective treatments can be devised. In the Abel laboratory, our focus is on cellular mechanisms and signaling cascades that regulate normal neural development and homeostasis, and how aberrant regulation of these pathways might contribute to brain cancer. In particular, we are interested in the putative role of neural stem cells and the transforming growth factor-beta signaling pathway in the pathogenesis of GBM. We use transgenic mice to model human glioma, focusing on genetic perturbations that are relevant in the human disease. Pathways of particular interest include the Ras and Akt pathways, as well as cell cycle regulators such as p53 and Cdkn2a.

We recently developed a novel mouse model of glioma (Abel, et al, 2009, Molecular Cancer Research, 7, 645-653). Glial fibrillary acidic acid (GFAP) is expressed in a subset of neural stem cells in a region of the brain known as the subventricular zone (SVZ). Ras is an key regulatory molecule in the Ras/Raf/MAPK cascade, a key signaling pathway that is hyperactive in human glioma. We used a mouse line that expresses Cre, under the control of the GFAP promoter, to activate oncogenic K-ras in GFAP-expressing cells in the mouse brain. These mice show a marked expansion of the SVZ, a major stem cell compartment in the brain. In addition, the mice develop glioma, which was often in close proximity to the expanded SVZ. Furthermore, the glioma cells expressed markers, including platelet derived growth factor receptor alpha, olig2 and Bmi-1, which are established markers of CNS stem cells. We concluded that activation of oncogenic K-ras in GFAP-expressing cells of the SVZ leads to aberrant migration of these cells into the surrounding brain parenchyma, and that these cells may be the source of the tumor in our model. Ongoing studies in the laboratory, using additonal in vivo as well as in vitro systems, aim to further define the relationships among molecular mechanisms regulating normal CNS stem cells and brain cancer cells.
Research Keywords
Pathobiology and experimental models of human brain cancer
Frierson JM, Pruijssers AJ, Konopka JL, Reiter DM, Abel TW, Stehle T, Dermody TS. Utilization of sialylated glycans as coreceptors enhances the neurovirulence of serotype 3 reovirus. J. Virol [print-electronic]. 2012 Dec; 86(24): 13164-73. PMID: 23035227, PMCID: PMC3503066, PII: JVI.01822-12, DOI: 10.1128/JVI.01822-12, ISSN: 1098-5514.

Ghazi SO, Stark M, Zhao Z, Mobley BC, Munden A, Hover L, Abel TW. Cell of origin determines tumor phenotype in an oncogenic Ras/p53 knockout transgenic model of high-grade glioma. J. Neuropathol. Exp. Neurol. 2012 Aug; 71(8): 729-40. PMID: 22805776, PMCID: PMC3407564, DOI: 10.1097/NEN.0b013e3182625c02, ISSN: 1554-6578.

Xu BJ, An QA, Srinivasa Gowda S, Yan W, Pierce LA, Abel TW, Rush SZ, Cooper MK, Ye F, Shyr Y, Weaver KD, Thompson RC. Identification of blood protein biomarkers that aid in the clinical assessment of patients with malignant glioma. Int. J. Oncol [print-electronic]. 2012 Jun; 40(6): 1995-2003. PMID: 22307528, DOI: 10.3892/ijo.2012.1355, ISSN: 1791-2423.

Cao D, Liu A, Wang F, Allan RW, Mei K, Peng Y, Du J, Guo S, Abel TW, Lane Z, Ma J, Rodriguez M, Akhi S, Dehiya N, Li J. RNA-binding protein LIN28 is a marker for primary extragonadal germ cell tumors: an immunohistochemical study of 131 cases. Mod. Pathol [print-electronic]. 2011 Feb; 24(2): 288-96. PMID: 21057460, PII: modpathol2010195, DOI: 10.1038/modpathol.2010.195, ISSN: 1530-0285.

Nickols HH, Chambless LB, Carson RP, Coffin CM, Pearson MM, Abel TW. Intramedullary spinal immature teratoma: resolution of quadriplegia following resection in a 4-week-old infant. J Neurosurg Pediatr. 2010 Dec; 6(6): 586-91. PMID: 21121736, DOI: 10.3171/2010.9.PEDS1022, ISSN: 1933-0715.

Harrison JF, Richard HT, Abel TW, Sosnowski JS, Martino AM. Gliomatosis cerebri: report of 3 cases. J Neurosurg Pediatr. 2010 Sep; 6(3): 291-4. PMID: 20809715, DOI: 10.3171/2010.5.PEDS09176, ISSN: 1933-0715.

Janz DR, Abel TW, Jackson JC, Gunther ML, Heckers S, Ely EW. Brain autopsy findings in intensive care unit patients previously suffering from delirium: a pilot study. J Crit Care [print-electronic]. 2010 Sep; 25(3): 538.e7-12. PMID: 20580199, PMCID: PMC3755870, PII: S0883-9441(10)00126-7, DOI: 10.1016/j.jcrc.2010.05.004, ISSN: 1557-8615.

Rush SZ, Abel TW, Valadez JG, Pearson M, Cooper MK. Activation of the Hedgehog pathway in pilocytic astrocytomas. Neuro-oncology [print-electronic]. 2010 Aug; 12(8): 790-8. PMID: 20223881, PMCID: PMC2940682, PII: noq026, DOI: 10.1093/neuonc/noq026, ISSN: 1523-5866.

Richard HT, Harrison JF, Abel TW, Maertens P, Martino AM, Sosnowski JS. Pediatric gliomatosis cerebri mimicking acute disseminated encephalomyelitis. Pediatrics [print-electronic]. 2010 Aug; 126(2): e479-82. PMID: 20624801, PII: peds.2009-2303, DOI: 10.1542/peds.2009-2303, ISSN: 1098-4275.

Chambless LB, Angel FB, Abel TW, Xia F, Weaver KD. Delayed cerebral radiation necrosis following treatment for a plasmacytoma of the skull. Surg Neurol Int. 2010; 1: 65. PMID: 21125009, PMCID: PMC2980905, DOI: 10.4103/2152-7806.71984, ISSN: 2152-7806.

Mei K, Liu A, Allan RW, Wang P, Lane Z, Abel TW, Wei L, Cheng H, Guo S, Peng Y, Rakheja D, Wang M, Ma J, Rodriguez MM, Li J, Cao D. Diagnostic utility of SALL4 in primary germ cell tumors of the central nervous system: a study of 77 cases. Mod. Pathol [print-electronic]. 2009 Dec; 22(12): 1628-36. PMID: 19820689, PII: modpathol2009148, DOI: 10.1038/modpathol.2009.148, ISSN: 1530-0285.

Sarangi A, Valadez JG, Rush S, Abel TW, Thompson RC, Cooper MK. Targeted inhibition of the Hedgehog pathway in established malignant glioma xenografts enhances survival. Oncogene [print-electronic]. 2009 Oct 10/1/2009; 28(39): 3468-76. PMID: 19617900, PMCID: PMC2756306, PII: onc2009208, DOI: 10.1038/onc.2009.208, ISSN: 1476-5594.

Abel TW, Clark C, Bierie B, Chytil A, Aakre M, Gorska A, Moses HL. GFAP-Cre-mediated activation of oncogenic K-ras results in expansion of the subventricular zone and infiltrating glioma. Mol. Cancer Res [print-electronic]. 2009 May; 7(5): 645-53. PMID: 19435821, PMCID: PMC3406747, PII: 1541-7786.MCR-08-0477, DOI: 10.1158/1541-7786.MCR-08-0477, ISSN: 1541-7786.

Reddy N, Abel TW, Jagasia M, Morgan D, Weaver K, Greer J. Progressive multifocal leukoencephalopathy in a patient with follicular lymphoma treated with multiple courses of rituximab. Leuk. Lymphoma. 2009 Mar; 50(3): 460-2. PMID: 19266387, PII: 909254836, DOI: 10.1080/10428190802695827, ISSN: 1029-2403.

Antar AA, Konopka JL, Campbell JA, Henry RA, Perdigoto AL, Carter BD, Pozzi A, Abel TW, Dermody TS. Junctional adhesion molecule-A is required for hematogenous dissemination of reovirus. Cell Host Microbe. 2009 Jan 1/22/2009; 5(1): 59-71. PMID: 19154988, PMCID: PMC2642927, PII: S1931-3128(08)00398-3, DOI: 10.1016/j.chom.2008.12.001, ISSN: 1934-6069.

Danthi P, Coffey CM, Parker JS, Abel TW, Dermody TS. Independent regulation of reovirus membrane penetration and apoptosis by the mu1 phi domain. PLoS Pathog [print-electronic]. 2008 Dec; 4(12): e1000248. PMID: 19112493, PMCID: PMC2600812, DOI: 10.1371/journal.ppat.1000248, ISSN: 1553-7374.

Stevenson CB, Ehtesham M, McMillan KM, Valadez JG, Edgeworth ML, Price RR, Abel TW, Mapara KY, Thompson RC. CXCR4 expression is elevated in glioblastoma multiforme and correlates with an increase in intensity and extent of peritumoral T2-weighted magnetic resonance imaging signal abnormalities. Neurosurgery. 2008 Sep; 63(3): 560-9; discussion 569. PMID: 18812968, PMCID: PMC2602832, PII: 00006123-200809000-00020, DOI: 10.1227/01.NEU.0000324896.26088.EF, ISSN: 1524-4040.

Sun DA, Yu H, Spooner J, Tatsas AD, Davis T, Abel TW, Kao C, Konrad PE. Postmortem analysis following 71 months of deep brain stimulation of the subthalamic nucleus for Parkinson disease. J. Neurosurg. 2008 Aug; 109(2): 325-9. PMID: 18671648, DOI: 10.3171/JNS/2008/109/8/0325, ISSN: 0022-3085.

Bierie B, Stover DG, Abel TW, Chytil A, Gorska AE, Aakre M, Forrester E, Yang L, Wagner KU, Moses HL. Transforming growth factor-beta regulates mammary carcinoma cell survival and interaction with the adjacent microenvironment. Cancer Res. 2008 Mar 3/15/2008; 68(6): 1809-19. PMID: 18339861, PII: 68/6/1809, DOI: 10.1158/0008-5472.CAN-07-5597, ISSN: 1538-7445.

Valentine WM, Abel TW, Hill KE, Austin LM, Burk RF. Neurodegeneration in mice resulting from loss of functional selenoprotein P or its receptor apolipoprotein E receptor 2. J. Neuropathol. Exp. Neurol. 2008 Jan; 67(1): 68-77. PMID: 18172410, PII: 00005072-200801000-00007, DOI: 10.1097/NEN.0b013e318160f347, ISSN: 0022-3069.

Danthi P, Kobayashi T, Holm GH, Hansberger MW, Abel TW, Dermody TS. Reovirus apoptosis and virulence are regulated by host cell membrane penetration efficiency. J. Virol [print-electronic]. 2008 Jan; 82(1): 161-72. PMID: 17959662, PMCID: PMC2224352, PII: JVI.01739-07, DOI: 10.1128/JVI.01739-07, ISSN: 1098-5514.

Ehtesham M, Sarangi A, Valadez JG, Chanthaphaychith S, Becher MW, Abel TW, Thompson RC, Cooper MK. Ligand-dependent activation of the hedgehog pathway in glioma progenitor cells. Oncogene [print-electronic]. 2007 Aug 8/23/2007; 26(39): 5752-61. PMID: 17353902, PII: 1210359, DOI: 10.1038/sj.onc.1210359, ISSN: 0950-9232.

Eberhart CG, Copeland J, Abel TW. Brief report: S6 ribosomal protein phosphorylation in autistic frontal cortex and cerebellum: a tissue array analysis. J Autism Dev Disord. 2006 Nov; 36(8): 1131-5. PMID: 16845579, DOI: 10.1007/s10803-006-0135-9, ISSN: 0162-3257.

Becher MW, Abel TW, Thompson RC, Weaver KD, Davis LE. Immunohistochemical analysis of metastatic neoplasms of the central nervous system. J. Neuropathol. Exp. Neurol. 2006 Oct; 65(10): 935-44. PMID: 17021398, PII: 00005072-200610000-00001, DOI: 10.1097/01.jnen.0000235124.82805.2b, ISSN: 0022-3069.

Abel TW, Curtis M, Lin DD, Burger PC, Cummings TJ. Complex choristoma of the gyrus rectus: a distinct clinicopathologic entity?. Am. J. Surg. Pathol. 2006 May; 30(5): 625-9. PMID: 16699317, PII: 00000478-200605000-00009, DOI: 10.1097/01.pas.0000194744.33540.28, ISSN: 0147-5185.

Stearns D, Chaudhry A, Abel TW, Burger PC, Dang CV, Eberhart CG. C-myc overexpression causes anaplasia in medulloblastoma. Cancer Res. 2006 Jan 1/15/2006; 66(2): 673-81. PMID: 16423996, PII: 66/2/673, DOI: 10.1158/0008-5472.CAN-05-1580, ISSN: 0008-5472.

Abel TW, Baker SJ, Fraser MM, Tihan T, Nelson JS, Yachnis AT, Bouffard JP, Mena H, Burger PC, Eberhart CG. Lhermitte-Duclos disease: a report of 31 cases with immunohistochemical analysis of the PTEN/AKT/mTOR pathway. J. Neuropathol. Exp. Neurol. 2005 Apr; 64(4): 341-9. PMID: 15835270, ISSN: 0022-3069.

Krajewski SJ, Abel TW, Voytko ML, Rance NE. Ovarian steroids differentially modulate the gene expression of gonadotropin-releasing hormone neuronal subtypes in the ovariectomized cynomolgus monkey. J. Clin. Endocrinol. Metab. 2003 Feb; 88(2): 655-62. PMID: 12574196, DOI: 10.1210/jc.2002-020887, ISSN: 0021-972X.

Abel TW, Rance NE. Stereologic study of the hypothalamic infundibular nucleus in young and older women. J. Comp. Neurol. 2000 Sep 9/4/2000; 424(4): 679-88. PMID: 10931489, PII: 10.1002/1096-9861(20000904)424:4<679::AID-CNE9>3.0.CO;2-L, ISSN: 0021-9967.

Abel TW, Rance NE. Proopiomelanocortin gene expression is decreased in the infundibular nucleus of postmenopausal women. Brain Res. Mol. Brain Res. 1999 Jun 6/8/1999; 69(2): 202-8. PMID: 10366741, PII: S0169328X99001114, ISSN: 0169-328X.

Abel TW, Voytko ML, Rance NE. The effects of hormone replacement therapy on hypothalamic neuropeptide gene expression in a primate model of menopause. J. Clin. Endocrinol. Metab. 1999 Jun; 84(6): 2111-8. PMID: 10372719, DOI: 10.1210/jcem.84.6.5689, ISSN: 0021-972X.

Korol DL, Abel TW, Church LT, Barnes CA, McNaughton BL. Hippocampal synaptic enhancement and spatial learning in the Morris swim task. Hippocampus. 1993 Apr; 3(2): 127-32. PMID: 8353599, DOI: 10.1002/hipo.450030204, ISSN: 1050-9631.

Available Postdoctoral Position Details
Posted: 7/25/2014