Posted November 29, 2011

Researchers examine the role of microRNAs in HIV-associated neuro-cognitive disorders

Bassel Sawaya, associate professor of neurology in Temple’s School of Medicine, has been awarded two Research Grants (RO1s) by the National Institutes of Health to examine and understand the role of microRNAs in the development of neurocognitive disorders associated with HIV.

The two grants, one for five years and another for three years with the potential for two additional years, total $2.96 million and will run concurrently.

“The major focus of my lab is to understand how HIV directly or indirectly causes neuronal degeneration,” said Sawaya. “An HIV patient, when they suddenly begin to lose the neurons in their brain, can develop neuro-cognitive disorders such as dementia. We are interested in identifying those mechanisms that could lead to such events.”

He and his collaborators will be working to identify the microRNAs (miRNAs) involved in neuronal dysfunction and loss, as well as their specific target genes impacted by released HIV-1 proteins such as Tat, Vpr and gp120.

Discovered in the early 1990s, miRNAs are small pieces of non-coding RNA that have the ability to regulate gene expression. MicroRNAs have been shown to play a role in reactivating latent virus in patients infected with HIV-1, in addition to their involvement in other neurodegenerative diseases such as Alzheimer’s and Parkinson’s, as well as in cancer and cardiovascular diseases.

“We want to identify genes associated with HIV that also play a role in neuronal function and are affected by these miRNAs,” said Sawaya. “If the gene is effected by these miRNAs, then the neurons are unhappy, which leads to neuronal dysfunction or loss and eventually to the development of neuro-cognitive disorders in patients infected with HIV-1.”

There are fewer than a handful of researchers at Temple working on miRNAs and very little research has been published on the role of miRNA in neuroAIDS, said Sawaya. “It is a largely understudied area.”

The two NIH RO1 grants have boosted the confidence of the researchers in his lab, said Sawaya.

“We are very excited and grateful that NIH recognizes the importance of our research, especially in this economic climate in which research funding is at a premium; to be able to secure two RO1 grants at the same time is very uncommon,” he said.

“The work being supported in our lab through these NIH grants in addition to our current grants will make the department of neurology at Temple one of the very few departments in the nation that study the link between miRNAs and neuroAIDS” said Sawaya.

Sawaya will be joined on the grants by Ruma Mukerjee, of the department of neurology; John Gaughan, of the department of physiology in the School of Medicine; and Vinjay Parikh, of the department of psychology in the College of Liberal Arts. He said the grant funding will also allow him to recruit four additional researchers for his lab.

Although his work is mostly in the basic sciences, Sawaya said there is a distinct benefit to working in a clinical department such as neurology.

“A lot of the things that I used to know about neuroAIDS were very minimal compared to what I have learned working in a clinical department,” he said. “I am able to interact with the department clinicians and go along on grand rounds where I can observe them discussing specific HIV cases.

“That has allowed me to see things from a really different angle and enlarge my view of specific neurological problems caused by HIV-1 infection and how best to attack those problems from the basic science perspective,” he said.