The five-year Program Project (P01) Grant through the National Institute for Neurological Disorders and Stroke, which will support 23 researchers and support staff over three projects, will continue the Center's ongoing investigation into the molecular biology and genetics of the interaction between viruses and host cells in the central nervous system.
"The program is basically an investigation into the neurological problems that are seen in AIDS patients," said Khalili. "We will be looking at HIV's effect on the nervous system to understand the molecular basis for the development and progression of neurological diseases that occur in some AIDS patients."
Khalili, who recently received Temple's Faculty Research Award, said that HIV can trigger the JC virus, which causes the fatal demyelinating disease Progressive Multifocal Leukoencephalopathy (PML), which occurs in some AIDS patients.
The JC virus infects greater than 70 percent of the human population worldwide during early childhood. According to Khalili, the JC virus most likely infects humans through the upper respiratory tract and remains in a latent stage in most people throughout their lives. However, in immunosuppressed individuals such as AIDS patients, the JC virus can become active and lead to the disease PML.
"We're going to investigate the molecular mechanisms that cause reactivation of the JC virus in AIDS patients," he said.
The researchers will be exploring these questions from many angles, several of which are extremely novel, including how the JC virus affects the integrity of the DNA by disregulating the host cell's DNA repair machinery.
"When the integrity of a cell's DNA is compromised, abnormalities such as apoptosis, or cell death, can occur," Khaili said. "So we'll be closely examining, among other things, how the virus causes this DNA repair dysfunction."
While PML remains a very rare disease in individuals not infected with HIV, adds Kahlili, a few patients recently enrolled in clinical trials of a novel treatment for another demyelinating disease, Multiple Sclerosis (MS), have developed the fatal disease prompting renewed interest in PML.
Accordingly, Khalili has taken the lead in rapidly setting up a workshop on JC virus and Multiple Sclerosis to bring clinicians and researchers together to evaluate the situation. An impressive group of world-class neurologists and neurovirologists attended a two day workshop held at Temple June 3-4 to discuss the potential risk of patients with MS for developing PML, including diagnostic and treatment strategies.
Khalili and his co-investigators in the CNVCB, who include Shohreh Amini, Nune Darbinian-Sarkissian, Luis Del Valle, Jennifer Gordon, Jay Rappaport, Krzysztof Reiss, Bassel Sawaya, Huichen Wang, and Martyn White, will also collaborate with Edward Johnson of the department of pathology at Mt. Sinai School of Medicine in New York on their newly funded grant.
The Center for Neurovirology and Cancer Biology now holds three current NIH P01 grants, with Khalili serving as principal investigator on two of them.