Title

Scientists garner 2nd top-level NIH grant to study HIV-1/AIDS neurological complications

Document Type

News Article

Publication Date

12-29-2014

Campus Unit

School of Medicine & Health Sciences

Abstract

GRAND FORKS, N.D.—In a time of reduced research funding, the National Institutes of Health granted $1.45 million to Chester Fritz Distinguished Professor Jonathan Geiger, PhD, and his colleague and collaborator Assistant Professor Xuesong Chen, MD, PhD, in the Department of Basic Sciences at the University of North Dakota School of Medicine and Health Sciences. This is the second, five-year R01 grant—the NIH's top-ranking—awarded to Geiger and Chen in the past four months. The grant from the NIH's National Institute of Mental Health funds research on novel mechanisms that regulate intracellular levels of calcium and how drugs used to treat HIV-1 infection affect these levels of calcium and interact with HIV-1 proteins to affect the mechanisms that control the levels of calcium inside of neurons.

Earlier this year, the Geiger and Chen laboratory received a $1.6 million 5-year NIH R01 grant for similar work that was focused on the effects of HIV-1 proteins on intraneuronal calcium control mechanisms. The novelty of both applications was recognized by the NIH grant review study section members. Geiger and Chen's unique insights and approaches resulted in their receiving these two R01 grants in one year.

"This is a huge achievement because it is so hard to get even one NIH R01 grant, let alone two," said Malak Kotb, PhD, the chair of the Department of Basic Sciences at the UND SMHS.

A part of the U.S. Department of Health and Human Services, the NIH is the nation's medical research agency. The NIH is the largest source of funding for medical research in the world. The mission of the NIH is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability.

"This further distinguishes Drs. Geiger and Chen from most other researchers because only the top 10 percent of grants are currently being funded by the NIH," said Joshua Wynne, MD, MBA, MPH, UND vice president for health affairs and dean of the UND School of Medicine and Health Sciences. "To receive two such grants probably puts them in the top 2 percent nationally."

Geiger and Chen are currently the only faculty members at UND that hold two NIH R01 grants.

Neurological complications associated with HIV-1 infection affect about 50 percent of patients living with HIV-1/AIDS. The mechanisms Geiger and Chen are studying might help explain why these patients are increasingly experiencing neurological complications that resemble those experienced by those individuals living with Alzheimer's disease.

For over 20 years, the Geiger laboratory has been studying neurological complications associated with HIV-1 infection, specifically HIV-1 associated neurocognitive disorders or HAND. Geiger's team has been working on studies aimed at determining the effects of HIV-1 proteins on neurons with a special focus on the involvement of intracellular calcium, a universally important signaling molecule.

"Our work highlights many of the good news and bad news stories associated with HIV-1 infection," Geiger said. "The bad news of course is that about 50 million people worldwide are infected with the virus. Bad news as well is that almost one-half of the infected people experience learning, memory and motor control difficulties. However, the good news is that antiretroviral drug therapies continue to get better and better and people are living longer lives. Of course, this means that people are experiencing and will increasingly experience age-related disorders, and it is hypothesized that HIV-1 proteins and the drugs used to treat HIV-1 infection are pro-aging."

The work that is funded by the two grants is focused on determining mechanisms by which HIV-1 proteins and some antiretroviral drugs cause neurons to be dysfunctional and to identify ways to prevent these problems. "It is interesting and potentially very important clinically that some of the drugs used to control the virus might also be part of the problem in terms of neurological complications," Geiger said. "We hypothesize that based on our work that drug regimens might be identified that still control viral replication but do not accelerate aging-related problems."

The NIH has long recognized the work of Geiger, who is the principal investigator for the UND Center of Biomedical Research Excellence or COBRE (pronounced "KOH-bree") for Neurodegenerative Disorder Research, which was originally funded in 2002. Funding for the Neurodegenerative Disorder Research COBRE has been renewed twice, most recently in 2012. By the end date for this grant in 2017, the NIH will have awarded to this COBRE-grant-funded group over $25 million.

The COBRE for Neurodegenerative Disorder Research seeks to answer questions about neurodegenerative diseases that loom large in health care, such as Alzheimer's disease, Parkinson's disease, neurological complications associated with HIV-1 infection, multiple sclerosis, and seizure disorders. Causes of these diseases are complex, so the COBRE's cadre of investigators are drawn from all the medical research disciplines at the SMHS. Translating their discoveries into treatments—"from lab bench to bedside"—is a crucial part of their work.

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