Jennifer Gordon, PhD
Associate Professor, Neuroscience
Associate Professor, Neurovirology
Location: Room 759 MERB
Department of Neuroscience
Center for Neurovirology
My research is focused on developing experimental animal models of neurological disorders including demyelination, neurodegeneration, and brain tumors. One of the main focuses in my lab is on the characterization of a Pur-alpha knockout mouse model which displays defects in neuronal development and differentiation. More specifically, the Pur-alpha knockout mouse model shows deficits in neuronal proliferation and migration as well as reduced levels of neurofilament phosphorylation and synaptic density. We have also identified dysregulation of Pur-alpha target proteins in our knockout mouse model including RhoA GTPase which Pur-alpha downregulates to induce neurite outgrowth, as well as other neuronal proteins such the Alzheimer's precursor protein (APP). These studies will impact on our understanding of AIDS pathogenesis in the CNS due to the established interaction between Pur-alpha and the HIV-1 Tat protein as well as cross talk between JC virus (JCV) and HIV-1. In the brain tumor project, we focus on the human neurotropic JC virus and its oncogenic protein, T-antigen, which targets tumor suppressor proteins leading to cellular transformation. JCV T-antigen transgenic mice develop malignant peripheral nerve sheath tumors seen in the autosomal dominant disorder, neurofibromatosis, and we have identified a new mechanism of JCV T-antigen induced tumorigenesis via interaction with the NF2 gene product, merlin. The development of several distinct phenotypes in these animal models, including a broad range of neural-origin tumors, has prompted the study of similar tumors in humans. Results of these studies have demonstrated the detection of JC virus DNA sequences and expression of the oncoprotein, T-antigen, in a large percentage of human medulloblastomas and astrocytic tumors, suggesting an association between JC virus and human CNS tumors. In addition to developing CNS tumors, our JCV T-antigen transgenic mice also can display a demyelinating phenotype and I have a long standing interest in studying the molecular pathogenesis and reactivation of JC virus and the demyelinating disease, progressive multifocal leukoencephalopathy, and the mechanisms of viral reactivation and immune system control of viral infection. Recently I have begun to study the role of stem cells in the development of cancer using our JCV T-antigen transgenic mouse models as a tool to uncover the relationship between stem cells and brain tumors. I also have a long standing interest in utilizing these models for developing novel in vivo MR imaging technologies. Recently, I have been studying tumor heterogeneity in glioblastoma and medulloblastoma, the mechanisms driving cancer cell survival and proliferation, and the role of the tumor microenvironment in the development and maintenance of brain tumors.
White, M.K., Gordon, J., and Khalili, K. (2013) The rapidly expanding family of human polyomaviruses: recent developments in understanding their life cycle and role in human pathology. PLoS Pathogens (in press).
Beltrami, S., Branchetti, E., Sariyer, I., Otte, J., and Gordon, J. (2013) Neurofibromatosis Type 2 tumor suppressor protein, NF2, induces proteasome-mediated degradation of JC virus T-antigen in human glioblastoma. PLoS One 8(1):e53447 PMID 23308224.
Beltrami, S., Kim, R., and Gordon, J. (2013) Neurofibromatosis Type 2: An unconventional cell cycle regulator. Anticancer Res. 33:1-11 PMID: 23267122.
Mishra, M., Del Valle, L., Otte, J., Darbinian, N., and Gordon, J. (2013) Pur-alpha regulates the developmental expression of RhoA and affects its downstream signaling ability in the mouse brain J. Cell. Physiol. 228:65-72 PMID: 22553010.
Johnson, E.M., Daniel, D.C., and Gordon, J. (2012) The Pur family: Genetic and structural features in development and disease. J. Cell. Physiol. (in press) PMID: 23018800.
Dang, X., Wuthrich, C., Gordon, J., Sawa, H., and Koralnik, I.J. (2012) JC virus encephalopathy is caused by a JCV variant with a novel deletion in the Agnoprotein gene. PLos One 7(4):e35793 PMID: 22536439.
Noch, E., Gordon, J., and Khalili, K. (2012) JC virus T-antigen regulates glucose metabolic pathways in brain tumor cells. PLoS One 7(4):e35054 PMID: 22496891.
Bouvard, H. et al, on behalf of the WHO International Agency for Research on Cancer Monograph Working Group. (2012) Carcinogenicity of malaria and of some polyomaviruses. (J. Gordon, member of the Working Group). Lancet Oncol. 13:339-40. PMID: 22577663.
Zhang, Y., Liu, J., Yao, S., Li, F., Xin, L., Lai, M., Bracchi-Ricard, V., Xu, H., Yen, W., Meng, W., Liu, S., Yang, L., Karmally, S., Liu, J., Zhu, H., Gordon, J., Khalili, K., Srinivasan, S., Bethea, J.R., Mo, X., and Hu, W. (2012) NFkB signaling initiates early differentiation of neural stem cells through suppression of C/EBP-beta. Stem Cells 30(3):510-24. PMID: 22134901.
Khalili, K., White, M.K., Gordon, J., and Krynska, B. (2012) Polyomavirus JC and human cancer: Possible role of stem cells in pathogenesis. In: Cancer associated viruses, Current Cancer Res. E.S. Robertson (ed.) pp. 433-448.
Uleri, E., Beltrami, S., Gordon, J., Dolei, A., and Sariyer, I.K. (2011) Extinction of tumor antigen expression by SF2/ASF in JCV-transformed cell lines. Genes and Cancer 2(7):728-36. PMID: 22207898.
Knight, L.C., Romano, J.E., Krynska, B., Faro, S., Mohamed, F.B., and Gordon, J. (2010) Binding and internalization of iron oxide nanoparticles targeted to nuclear oncoprotein. J. Mol. Biomark. Diagn. J. Mol. Biomark. Diagn. 1:102-107.
Tremolada, S., Akhan, S., Otte, J., Khalili, K., Ferrante, P., Roy-Chaudhury, P., Woodle, E.S., Trofe-Clark, J., White, M.K., and Gordon, J. (2010) Rare subtypes of BK virus are viable and frequently detected in renal transplant recipients with BK virus-associated nephropathy Virology 404(2):312-8 PMID: 20554301.
Del Valle, L., Pina-Oviedo, S., Perez-Liz, G., Augelli, B.J., Azizi, A., Khalili, K., Gordon, J. and Krynska, B. (2010) Bone marrow-derived mesenchymal stem cells undergo JCV T-antigen mediated transformation and generate tumors with neuroectodermal characteristics. Cancer Biol. Ther. 16;9(4) PMID: 20190567.
Tremolada S, Delbue S, Castagnoli L, Allegrini S, Miglio U, Boldorini R, Elia F, Gordon J, Ferrante P. (2010) Mutations in the external loops of BK virus VP1 and urine viral load in renal transplant recipients. J. Cell. Physiol. 222(1):195-9 PMID: 19780025.
Stettner, M.R., Nance, J.A., Wright, C., Kinoshita, Y., Kim, W.-K., Morgello, S., Rappaport, J., Khalili, K., Gordon, J. and Johnson, E.M. (2009) SMAD Effectors of TGF-b Regulate Transcription of JC Viral Early and Late Genes in Glial Cells Coordinately with the Tat Protein Of Human Immunodeficiency Virus Type I. J. Gen. Virol. 90:2005-14 PMID: 19420158.
Sariyer, I.K., Safak, M., Gordon, J., and Khalili, K. (2009) Generation and charcterization of JCV permissive hybrid cell lines. J. Virol. Methods 159:122-6 PMID: 19442856.
Darbinian, N., Cui, J., Basile, A., Del Valle, L., Miklossy, J., Sawaya, B.E., Amini, S., Khalili, K., and Gordon, J. (2008) Negative regulation of AbetaPP gene expression by Pur-alpha. J. Alzheimer's Dis. 15:71-82 PMID: 18780968.
Chen, Y., Trofe, J., Gordon, J., Autissier, P., Woodle, E.S., and Koralnik, I.J. (2008) BKV and JCV large T antigen-specific CD8+ T cell response in HLA A*0201+ kidney transplant recipients with polyomavirus nephropathy and patients with progressive multifocal leukoencephalopathy. J. Clin. Virol. 42:198-202 PMID: 18295538.
Draberova, E., Del Valle, L., Gordon, J., Markova, V., Smejkalova, B., Bertrand, L., de Chadarévian, J.-P., Agamanolis, D.P., Legido, A., Khalili, K., Draber, P., Katsetos, C.D. (2008) Class III beta-tubulin is constitutively co-expressed with glial fibrillary acidic protein and nestin in midgestational human fetal astrocytes: Implications for phenotypic identity. J. Neuropathol. Exp. Neurology 67:341-54 PMID: 18379434.
Darbinian, N., Darbinyan, A., Czernik, M., Peruzzi, F., Khalili, K., Gordon, J., and Amini, S. (2008) HIV-1 Tat inhibits NGF-induced Egr-1 transcriptional activity and consequent p35 expression in neuronal cells. J. Cell. Physiol. 216:128-34 PMID: 18247371.
Lima, M.A., Marzocchetti, A., Autissier, P., Tompkins, T., Chen, Y., Gordon, J., Clifford, D.B., Gandhi, R.T., Venna, N., Berger, J.R., and Koralnik, I.J. (2007) Frequency and phenotype of JC virus-specific CD8+ T lymphocytes in the peripheral blood of patients with progressive multifocal leukoencephalopathy. J. Virol. 81:3361-3368 PMID: 17229701.
White, M.K., Skowronska, A., Gordon, J., Del Valle, L., Deshmane, S.L., Giordano, A., and Khalili, K. (2006) Analysis of a mutant p53 protein arising in a medulloblastoma from a mouse transgenic for the JC virus early region. Anticancer Res. 26:4079-4092 PMID: 17201119.
Darbinian-Sarkissian, N., Czernik, M., Peruzzi, F., Gordon, J., Rappaport, J., Reiss, K., Khalili, K., and Amini, S (2006) Dysregulation of NGF signaling and Egr-1 expression by Tat in neuronal cell culture. J. Cell. Physiol. 208:506-15 PMID: 16741963.
Khalili K, Gordon J, White MK, (2006) The polyomavirus, JCV and its involvement in human disease. Adv Exp Med Biol 577:(274-87) PMID: 16626043.
Sariyer, I.K., Akan, I., Palermo, V., Gordon, J., Khalili, K., and Safak, M. (2006) Phosphorylation mutants of JC agnoprotein are unable to sustain viral infection cycle. J. Virol. 80:3893-903 PMID: 16571806.
Chen, Y., Trofe, J., Gordon, J., Du Pasquier, R.A., Roy-Chaudhury, P., Kuroda, M.J., Woodle, E.S., Khalili, K., and Koralnik, I.J. (2006) Interplay of the cellular and humoral immune response against BK virus in kidney transplant recipients with polyomavirus nephropathy. J. Virol. 80:3495-505 PMID: 16537617.
Johnson, E.M., Kinoshita, Y., Weinreb, D.B., Wortman, M.J., Simon, R., Amini, S., Khalili, K., Winckler, B., and Gordon, J. (2006) Role of Pur-alpha in targeting mRNA to sites of translation in hippocampal neuronal dendrites. J. Neurosci. Res. 83:929-43 PMID: 16511857.