Madhu Sukumar – Research

In 1996 the introduction of “triple cocktail” drug therapy transformed AIDS from a death sentence into a manageable chronic disease. The drug regimen, also known as HAART for highly active antiretroviral treatment, involved treating patients with three or more classes of antiviral medicines.

But the virus fought back. It mutates easily, and the mutations caused resistance to first one and then another drug making up the cocktail. Unsettling reports of newly infected patients with the drug-resistant virus meant researchers needed to find new ways to fight HIV infection.

That could be what is happening in the Dedman Life Sciences Building at SMU, where a young assistant professor of biological sciences is conducting research that may lead to a novel way of combating HIV-1.

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In his office in Dedman College’s Department of Biological Sciences, Assistant Professor Robert Harrod talks about an exciting discovery his research team made last year. The discovery involves the way viruses replicate and the disease Werner syndrome, a rare genetic disorder that causes premature aging.

The HIV-1 virus infects white cells involved in fighting infection, inserting itself into the genetic material of the cells, commonly known as T-cells, to cause AIDS. Once the virus is integrated into the host cell, Harrod explains, it is dependent on “human cellular transcription factors” to replicate. The researchers have shown that the Werner syndrome enzyme is an essential factor in that transcription process. They reasoned if they could inhibit the enzyme function, they could block the transcription.

Using cells developed by researchers at the University of Washington who are studying Werner syndrome, the SMU researchers were able to insert the enzyme defect that causes Werner syndrome into HIV-infected T-cells, blocking 95 percent of retroviral transcription. If the HIV/AIDS virus can’t be transcribed, it can’t replicate.

The one in 1,000 people in Japan who are Werner syndrome carriers (without developing the syndrome) have not been observed to develop AIDS, Harrod points out, suggesting that affecting the functioning of the enzyme that causes Werner syndrome is a plausible way to fight HIV/AIDS.

The beauty of the Werner syndrome-enzyme approach to HIV/AIDS treatment is that the virus can’t mutate to defeat treatment, Harrod says.

The HIV-inhibition research was published in the April 20, 2007 issue of “The Journal of Biological Chemistry.”

Harrod’s research group, which includes Master’s degree student Madhu Sukumar and three biological sciences undergraduates, now is searching for molecules that will inhibit the function of the Werner syndrome enzyme, and thus, viral replication.

Harrod’s work also is an example of the international collaboration that is occurring to find solutions to global health issues. He is collaborating on the research with Antonito Panganiban from the University of New Mexico-Health Sciences Center, Carine Van Lint from the Universite Libre de Bruxelles and two clinical researchers, Dennis Burns and Daniel Skiest, from UT Southwestern Medical Center at Dallas.

According to the World Health Organization, 33 million people are living with HIV/AIDS worldwide. That is why Professor William Orr, chair of Biological Sciences at SMU, calls Harrod’s research exciting.

“It’s going to provide an alternative way in which one might be able to deactivate or slow down this scourge,” Orr says.

Harrod joined SMU in 2002 and teaches undergraduate and graduate students. He earned his Ph.D. at the University of Maryland in 1996, and received postdoctoral training at the National Institutes of Health and the Naval Medical Center. — Cathy Frisinger