The National Institute of Mental Health, a division of the National Institutes of Health (NIH), has awarded an R01 grant titled “Tat endolysosome escape and HIV-1 associated neurocognitive disorder” to Drs. Xuesong Chen and Jonathan Geiger. Both are faculty members in the Department of Biomedical Sciences at the University of North Dakota School of Medicine & Health Sciences, where Dr. Geiger is a Chester Fritz Distinguished Professor. This five-year grant has a total value of about $2.2 million.
Making the award notice more remarkable is the fact that the researchers now have five active NIH R01 grants between them—three from the National Institute of Mental Health, one from the National Institute of Neurological Diseases and Stroke, and one from the National Institute of Drug Abuse. NIH R01 grants are considered one of the most prestigious grants for which researchers can apply, and funding for these grants is extremely competitive.
This latest grant will focus on determining the mechanisms responsible for neurological complications that occur in people living with HIV-1.
“Although great progress has been made in treating HIV-1 such that people living with HIV-1 are now living almost full life spans, almost 50 percent still experience a syndrome termed HIV-1 associated neurocognitive disorder, or HAND,” Dr. Chen said.
One HIV-1 protein that has been implicated in the pathogenesis of HAND is the transactivator of transcription (Tat). This non-structural protein is required for replication of the virus, and is actively secreted from HIV-1 infected cells. It can also directly excite neurons and cause nerves to be dysfunctional.
“We have worked on HIV-1 Tat neurotoxicity for almost 20 years, and much is now known about the mechanisms by which Tat affects neurons,” Dr. Geiger said.
Over the past five years, Drs. Chen and Geiger have focused much of their research on the involvement of the intracellular organelles—subunits within cells that have specific functions—known as endosomes and lysosomes (or “endolysosomes”) in the actions of HIV-1 Tat.
“The current grant is specifically focused to determine the mechanisms by which Tat escapes endolysosomes and the extent to which this escape contributes to neuronal injury,” Geiger continued. “The results are expected to provide us with new targets and rationale for preventative and therapeutic interventions against HAND. It goes without saying that the outcome of the proposed studies could have a substantial, global impact economically, socially, and clinically.”