D’Souza Takes New Approach to Fighting AIDS

With global AIDS advocacy culminating last Friday on World AIDS Day, Harvard AIDS activists spent a busy week flocking from one speaker event to another, tying red strips on tree trunks, and decking Grays Hall with a giant red ribbon made out of Christmas lights.

But sitting quietly in her lab, Victoria D’Souza, the Molecular and Cellular Biology (MCB) Department’s new and only HIV virologist, is doing the actual fighting with the villain behind it all—the Human Immunodeficiency Virus (HIV).

“The scary part is that in some of the countries like China, India, and Russia, HIV infection is rapidly on the rise,” D’Souza says with a grim face. “We know what’s happened in Africa and you don’t want the same thing to be repeated in the developing countries.”

Although upmost in most people’s minds is probably a cure for AIDS, D’Souza says that search “hasn’t been very promising.”

Instead, she has chosen to concentrate on finding treatments that will render the disease “insignificant in the lifetimes of people.” D’Souza, who assumed her professorship this past July, says she hopes to do her part to minimize the number of people suffering from the virus, which has newly infected 4.3 million people so far this year.

AN ALTERNATIVE APPROACH

D’Souza’s approach to HIV research is unique because she uses structural biology. Her research focuses on the first step of the viral life cycle of HIV—the process of reverse transcription—in which the virus changes its genome from RNA to DNA.

Currently, most anti-HIV drugs target individual proteins, and are given in combination as a cocktail. However, according to D’Souza, HIV is mutating and building up resistance to the cocktail. By studying the RNA-protein complex, which is crucial to the virus’ survival, D’Souza aims to sophisticate the current approach to AIDS treatment.

D’Souza’s research topic “is a fascinating problem that has been very difficult for others to tackle,” says Associate Professor Rachelle Gaudet, D’Souza’s colleague in the MCB department and a fellow structural biologist.

“It’s really at the cutting edge of structural biology of RNA,” she says.

In the next three to four years, D’Souza says she should be close to solving the structure of the RNA-protein complex, which is, according to her, “probably the most difficult part.”

The next step would be to conduct drug-binding experiments. According to D’Souza, an effective drug would target the interaction between RNA and the reverse transcriptase protein, unlike current drugs which target just the protein.

D’Souza has been given a three-year, $300,000 grant from the Damon Runyon Cancer Research Foundation—awarded to five outstanding researchers during the initial years of their first faculty position.

LOVIN’ THE ‘REALLY TINY THINGS’

D’Souza says she would not be able to tear herself away from virology even if she were not doing HIV research, because of her love for microbes.

“The whole virology field fascinates me. These are really tiny things with very tiny genomes and they trick so many organisms and species into not knowing how to fight them,” she says.

Ironically, D’Souza made her name by mapping out the structure of the largest RNA molecule using the nuclear magnetic resonance technique. “There are very few structural biologists who want to work with very large molecules,” D’Souza says. Before D’Souza’s work delineating the structure of an encapsidation signal of the murine leukemia retrovirus, researchers had only done the same for molecules of about half that size.

This research, through which D’Souza became known in the field, was conducted at the University of Maryland at Baltimore County (UMBC), where she received her Ph.D. and spent her postdoctorate days before coming to Harvard.

Here, D’Souza says she is eager to share her love for the microscopic with students. She dreams of building her intellectual army of “people trying to understand the smallest level in the human body,” D’Souza says.

ENLISTING FRESH MINDS

The University typically does not give teaching responsibilities to first-year researchers, allowing them time to set up their laboratories—but D’Souza will be giving two guest lectures on HIV in this year’s MCB 52, “Molecular Biology.”

Eventually, she says that she would like to teach an undergraduate course. When asked if teaching was a way for her to enlist the best and brightest to join her research team, D’Souza breaks into a wide smile and says, “Yes, that’s the whole idea.”

D’Souza says she is used to working with young students from her experience at UMBC. Three of the five she has recruited to work for her project are undergraduates, two of them freshmen.

Gaudet says that one of the reasons D’Souza is such a great addition to the MCB department is her commitment to teaching and mentoring undergraduates.

Zachary A. Katz ’10, one of D’Souza’s freshmen who hopes to concentrate in MCB and English, says he discovered D’Souza’s lab by “a stroke of luck,” and that he hopes to work there until he graduates. “What really interested me about her research was her novel idea to look at RNA-protein interactions...it’s something that could probably have a higher payoff,” Katz says.

Come April, in addition to her roles as a mentor and researcher, D’Souza will also be a mother. Even though she says she tries to heed doctors’ orders and works as much as possible from home, she admits with a chuckle that she usually has twelve-hour work days.

But D’Souza says the baby will not stall her in her efforts to fight the virus.