Kamel Khalili
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Office: Department of Biology Center for Neurovirology and Cancer Biology Phone: (215) 204-0678
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The major thrust of our future research will rest on better understanding of the molecular pathogenesis of viral- and non-viral-induced neurological diseases. We are investigating the reciprocal interaction between cellular proteins as well as viral and cellular proteins which may play an important role in the de-regulation of the events leading to genesis of disease in cells of the central nervous system (CNS). More specifically, we are focusing on progressive multifocal leukoencephalopathy (PML), a disease which is induced upon reactivation of JC virus in the CNS. Earlier studies from our laboratory have led to the identification of several regulatory proteins which play an important role in the reactivation of JCV in oligodendrocytes, the myelin-producing cells of the CNS. We are planning to employ genetic approaches to manipulate expression of these genes in the CNS and to develop molecular therapeutic strategies to interfere with the function of these proteins on JC virus. In a different set of studies, in collaboration with Dr. Amini and Dr. Sawaya from the Center for Neurovirology and Cancer Biology, we have focused our attention on AIDS and replication of HIV-1 in CNS cells. In this respect, we are investigating viral regulatory proteins such as Vpr and Tat. Vpr is a protein which has been shown by many laboratories, including our own, to be important for transcription of viral genes. In addition, recent studies in our laboratory point to the interaction of Vpr with another critical viral regulatory protein, Tat. In this respect, we are planning to devise regulatory molecules to genetically manipulate Vpr and Tat which interfere with the function of the wild-type protein in the CNS. The results of these manipulations will help us to investigate the regulatory events important for function of these proteins and also to develop therapeutic modalities against HIV-1 replication. In a third series of studies, we will focus our attention on tumors and the pathogenesis of neoplasms in the CNS. We have developed several experimental animal models with the ability to form tumors during various stages of life. These in vivo animal models will be used in our laboratory to better understand the molecular pathways involved in the formation and progression of tumors in the CNS. Indeed, the results from these observations will enable us to develop therapeutic strategies which effectively block progression of cancer in brain. As such, as evidenced from above statement, our future strategy will rest on translational research where we will utilize our experience in studying eukaryotic gene expression in the CNS to develop strategies for the treatment of a variety of CNS diseases, such as PML, AIDS, and brain tumors. More recently, we have instituted several research projects aimed at developing vaccines against the human neurotropic virus, JCV, in humans
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