Title: Associate Professor, Burnham Institute for Medical Research
Education: PhD, Stanford University, 2001
Recommended by: John Reed
When it comes to using systems biology to invigorate drug discovery and development, Sumit Chanda has a tailor-made background. An associate professor of infectious and inflammatory diseases at the Burnham Institute in San Diego, Chanda spends his time looking for HIV drug targets. "We're using tools in systems biology to dissect viral host-pathogen interaction," he says, citing large-scale RNAi screening, protein interaction mapping, chemical genomics, and basic biology tools as some of the methods he uses in his lab "to unravel host-pathogen interactions that are required for viral replication."
Chanda says that most viruses are small, having only a handful of druggable genes, and they are good at mutating and becoming resistant to drugs or compounds used to treat them. "What [our work] enables us to do is go after cellular proteins — [the virus] obviously can't mutate a cellular protein," he says. "So if we can target a cellular protein that the virus needs, then it [becomes] a whole new ball game in trying to develop novel antivirals. The great hope is that we're going to be able to develop drugs that get around this issue of resistance."
If Chanda brings a lot of different avenues to his work, it's because of his diverse background. He did his PhD at Stanford University in the late '90s working with microarray pioneers Pat Brown and David Botstein. "I pretty much grew up on functional genomics and that was kind of my world view at the time," he says. He then went to the Genomics Institute of the Novartis Research Foundation as a fellow, where he was able to "build new technologies to extend the paradigm of microarray analyses." There, he set up a technology platform that would later become the basis for his current RNAi screening techniques.
He says his time at Stanford really had an impact on his research. "At Stanford, the microarray was just an absolutely novel paradigm at the time — it was really a brave new world, so that really changed my scientific world view," he says.
In the next five years, Chanda would like to see the gap bridged not only between academics and pharmaceutical scientists, but also between systems biology and wet lab work. "I really think it needs to be a continuum and not two different communities," he adds.
He also says that if there isn't an HIV antiviral compound targeting a host cell protein, there should be serious effort underway to develop one. "We're running out of targets in HIV," he says. "If you take a look at swine flu, there's one drug right now that can work against it. Once it becomes resistant, that's it, there are no antivirals left. So we really have to go and expand the kinds of targets we're going after. Same with HIV — there [are] only so many druggable proteins in the HIV genome."
Publications of note
In a paper that came out in Cell in 2008, Chanda led work that used a multiscale approach to look for factors important during the early stages of HIV infection. Combining a genome-wide RNAi screen with data from a human interactome database, his team built a host-pathogen network of 213 host cell factors and 11 HIV-1-encoded proteins that are important in infection. Chanda says the large-scale RNAi screen allowed them to ask, "Which genes are not killing the cells but are blocking HIV's ability to replicate in the cell?" They found proteins that regulate ubiquitin conjugation, proteolysis, DNA damage response, and RNA splicing.
And the Nobel goes to...
Chanda says he'd like to win the Nobel Prize for curing a disease. "Although I love the intellectual pursuit, ultimately I would like to see my work have a practical impact on people's lives and on human health," he says.