2019 Paradigm Builder Lectureship Kamel Khalili Professor and Chair of Neuroscience Temple University School of Medicine

The International Society for NeuroVirology has honored Dr. Kamel Khalili with the 2019 Paradigm Builder Award for his numerous and outstanding contributions to the field. Dr. Khalili is Chair of the Department of Neuroscience and Director of the Center for Neurovirology at Temple University School of Medicine in Philadelphia. Khalili employed molecular strategies to understand pathways by which human neurotropic viruses inflict injuries to brain, especially to glial cells, and ensure their persistent and productive infection. He has extensively studied the glial tropic JC virus, the etiologic agent of the fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML), a long-standing project that has led him to identify several novel proteins and pathways, including Pur alpha, a single stranded nucleic acid binding protein. He showed that the Tat protein of HIV augments JCV replication, offering a mechanistic model for the higher incidence of PML observed in individuals with AIDS. Further, he and his team uncovered a novel mechanism by which Tat activates the HIV promoter via recruitment of NF𝝹B. Khalili’s extensive investigation of the oncogenic potential of JC virus in cell and animal models gave him the opportunity to discover several pathways that are perturbed by the JCV regulatory proteins, T-antigen and Agnoprotein. Interestingly, both of these proteins were detected in the several types of human brain tumors. In the last few years, Khalili and his colleagues have pioneered the employment of a CRISPR-based gene editing strategy for complete eradication of HIV in infected cells by excising the entire integrated viral DNA from the host chromosome, with no off-target effects. This technique has been effective for inactivating HIV ex vivo, in HIV patient samples, and in vitro, in several animal models.

These results include evidence, for the first time, that HIV can be eliminated from HIV infected mice. These efforts offer new alternative avenues for permanent inactivation of HIV in the clinic. His team has developed gene editing technology for inactivation of neurotropic viruses including JCV and HIV. Khalili’s persistent and impactful contributions to science for over 30 years have earned him the Pioneer in NeuroVirology Award by his peers. In addition, he has trained over twenty-three graduate students, seventeen M.D./Ph.D. students, fifty-four postdoctoral fellows and eighteen visiting scholars. Dr. Khalili has also authored over 450 scholarly publications in highly regarded journals. Congratulations Dr. Khalili for your outstanding contributions.