Ty William Abel, M.D., Ph.D.
- Associate Professor of Pathology, Microbiology and Immunology
Dr. Ty W. Abel is an Associate 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.
- 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
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.
- 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.