Ty Abel
Faculty Member
Last active: 3/27/2014

Profile

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.

Publications

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. Apoptosis induction influences reovirus replication and virulence in newborn mice. Pruijssers AJ, Hengel H, Abel TW, Dermody TS (2013) J Virol 87(23): 12980-9
    › Primary publication · 24067960 (PubMed) · PMC3838116 (PubMed Central)
  2. Vascular complications of fungal meningitis attributed to injections of contaminated methylprednisolone acetate. Kleinfeld K, Jones P, Riebau D, Beck A, Paueksakon P, Abel T, Claassen DO (2013) JAMA Neurol 70(9): 1173-6
    › Primary publication · 23877880 (PubMed) · PMC4143418 (PubMed Central)
  3. Identification of blood protein biomarkers that aid in the clinical assessment of patients with malignant glioma. 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 (2012) Int J Oncol 40(6): 1995-2003
    › Primary publication · 22307528 (PubMed)
  4. Pituitary blastoma: a unique embryonal tumor. Scheithauer BW, Horvath E, Abel TW, Robital Y, Park SH, Osamura RY, Deal C, Lloyd RV, Kovacs K (2012) Pituitary 15(3): 365-73
    › Primary publication · 21805093 (PubMed)
  5. Loss of one Tgfbr2 allele in fibroblasts promotes metastasis in MMTV: polyoma middle T transgenic and transplant mouse models of mammary tumor progression. Fang WB, Jokar I, Chytil A, Moses HL, Abel T, Cheng N (2011) Clin Exp Metastasis 28(4): 351-66
    › Primary publication · 21374085 (PubMed) · PMC3373018 (PubMed Central)
  6. Membrane-type 4 matrix metalloproteinase (MT4-MMP) modulates water homeostasis in mice. Srichai MB, Colleta H, Gewin L, Matrisian L, Abel TW, Koshikawa N, Seiki M, Pozzi A, Harris RC, Zent R (2011) PLoS One 6(2): e17099
    › Primary publication · 21347258 (PubMed) · PMC3037967 (PubMed Central)