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Sights Set on HIV

  • Title: Assistant Professor, George Mason University
  • Education: PhD, Queen's University, 1998
  • Recommended by: Emanuel Petricoin

Several years ago, finding a cure for AIDS seemed like a lofty goal, but with ‘omic techniques gaining ground and someone like Yuntao Wu’s enthusiasm, solving this puzzle might be closer than you think. Wu, who’s been assistant professor of molecular and microbiology at George Mason University since 2003, is studying HIV infection in resting CD4 T cells, which is where the virus predominately replicates. Specifically, he’s studying the changes that happen after infection, and what signaling transduction pathways are initiated inside the cell. Wu’s eventual goal is to find some kind of inhibitor that “can prevent or slow down the killing of those CD4 T cells.”

Wu recently received a two-year, $393,000 NIH grant, which he’s spent building a lentiviral vector that carries a toxic gene from the Bacillus anthracis bacterium. The vector would attack HIV-infected cells, promote viral degradation of the HIV virus, and prevent HIV from attacking healthy cells. While this work is still in the lab, he’s hoping to move to animal experiments soon and, eventually, to clinical trials.

Wu spent his PhD in Eric Carsten’s lab at Queen’s University, Kingston, Ontario, Canada. While there, he worked on ways to manipulate baculoviruses, which typically infect moths, mosquitoes, and other insects. Deciding to change focus to study a virus that affects humans, he began a four-year research fellowship at NIH’s National Institute of Mental Health in 1999, working on a project studying pre-integration transcription in HIV infection of CD4 T cells. Along with his advisor, Jon Marsh, he published a paper in Science in 2001 (“Selective Transcription and Modulation of Resting T Cell Activity by Preintegrated HIV DNA”) that examined the transcript population of resting CD4 T cells and found that HIV infection leads to selective transcription of two particular genes, nef and tat, before it’s actually integrated into the host chromatin. The activity leads to increased activation in T cells and subsequently, to viral replication. “It’s unexplored,” Wu says of studies on resting T cells. “There’s a lack of a lot of basic information.”

Recently Wu submitted a paper to Cell, compiling five years’ worth of research on CXCR4 signaling in HIV-1 infection of resting CD4 T cells. He’s hoping that the publication of these results will both enlighten the field and win him more grant money. “We are very excited about our new discoveries,” he says. “[It] has puzzled the field for a decade.”

Funding is a key hurdle for Wu, and currently he’s waiting for a grant that will keep his research on track for the next five years. “Funding is really a challenging issue,” he says. “Once we have that funding, I think the lab is going to be very solid. Actually we have a lot of good data — we just need to have new funding to push them forward.”

Looking ahead

As for the field of HIV research as a whole, Wu sees the focus on finding a vaccine premature, but not because it’s impossible. “The field has to go back to looking for basic science, really looking for the interaction of the virus with the immune cells,” he says. Taking a step back will allow a more complete understanding of the immune system’s reaction to HIV, which eventually could lead to improved toolsets to monitor disease progression, or drugs that could slow down the virus. An imagined new technology development that would greatly help Wu’s research, he says, would be an imaging tool that could actually track the HIV molecule and its migration into the host cell.

And the Nobel goes to ....

Not one to shrink from a challenge, Wu says he would be more than happy to win the Nobel Prize for finding either a cure for AIDS or discovering some way to slow down the progression of the disease.           

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