Ty William Abel, M.D., Ph.D.
Associate Professor of Pathology, Microbiology and Immunology
Dr. Ty W. Abel is an Assistant Professor of Pathology in the Neuropathology Division. He completed his residency and fellowship at The Johns Hopkins Hospital and joined the Vanderbilt faculty in 2005. His clinical interest and expertise are in the histopathologic diagnosis of brain and spinal cord tumors.
Pathobiology and experimental models of human brain cancer
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.
Diagnostic surgical and autopsy neuropathology
- Rush, SZ, Abel, TW, Valadez, JG, Pearson, M, Cooper, MK Activation of the Hedgehog pathway in pilocytic astrocytomas. Neuro Oncol, 2010.
- 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, 25(3), 538.e7-12, 2010.
- 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, 165, 2010.
- Harrison, JF, Richard, HT, Abel, TW, Sosnowski, JS, Martino, AM Gliomatosis cerebri: report of 3 cases. J Neurosurg Pediatr, 6(3), 291-4, 2010.
- 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, 6(6), 586-91, 2010.
- Richard, HT, Harrison, JF, Abel, TW, Maertens, P, Martino, AM, Sosnowski, JS Pediatric gliomatosis cerebri mimicking acute disseminated encephalomyelitis. Pediatrics, 126(2), e479-82, 2010.
- 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, 2010.
- 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, 22(12), 1628-36, 2009.
- 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, 7(5), 645-53, 2009.
- 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, 5(1), 59-71, 2009.
- 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, 50(3), 460-2, 2009.
- 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, 2009.
- 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, 63(3), 560-9; discussion 569-70, 2008.
- 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, 4(12), e1000248, 2008.
- 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, 67(1), 68-77, 2008.
- 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, 109(2), 325-9, 2008.
- 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, 82(1), 161-72, 2008.
- 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, 68(6), 1809-19, 2008.
- 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, 26(39), 5752-61, 2007.
- 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, 2007.
- 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, 36(8), 1131-5, 2006.
- Abel, TW, Curtis, M, Lin, DD, Burger, PC, Cummings, TJ Complex choristoma of the gyrus rectus: a distinct clinicopathologic entity. Am J Surg Pathol, 30(5), 625-9, 2006.
- Becher, MW, Abel, TW, Thompson, RC, Weaver, KD, Davis, LE Immunohistochemical analysis of metastatic neoplasms of the central nervous system. J Neuropathol Exp Neurol, 65(10), 935-44, 2006.
- Stearns, D, Chaudhry, A, Abel, TW, Burger, PC, Dang, CV, Eberhart, CG c-myc overexpression causes anaplasia in medulloblastoma. Cancer Res, 66(2), 673-81, 2006.
- 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, 64(4), 341-9, 2005.
- 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, 88(2), 655-62, 2003.
- Abel, TW, Rance, NE Stereologic study of the hypothalamic infundibular nucleus in young and older women. J Comp Neurol, 424(4), 679-88, 2000.
- Abel, TW, Rance, NE Proopiomelanocortin gene expression is decreased in the infundibular nucleus of postmenopausal women. Brain Res Mol Brain Res, 69(2), 202-8, 1999.
- 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, 84(6), 2111-8, 1999.
- Korol, DL, Abel, TW, Church, LT, Barnes, CA, McNaughton, BL Hippocampal synaptic enhancement and spatial learning in the Morris swim task. Hippocampus, 3(2), 127-32, 1993.
M.D. - University of Arizona, 2001
Ph.D. - University of Arizona, 1999
Fellowship - Johns Hopkins Hospital and Health System
Residency - Johns Hopkins Hospital and Health System