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PhD, Molecular Pathobiology, Drexel (MCP Hahnemann) School of Medicine, 1999
BS, Biology, Albright College, 1990
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.
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