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Tackling Susceptibility Genes and Disease

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  • Title: Assistant Professor, University of Southern California
  • Education: PhD, University of California, Los  Angeles, 1999
  • Recommended by: Laurence Kedes

Hooman Allayee is one geneticist looking to find the big connections between complex pathologies such as cardio-vascular disease, obesity, and diabetes. “We are trying to find the genes that cause these diseases,” says Allayee. “They are related because diabetics have an increased risked of heart disease, and with obesity, there is an increased risk of diabetes, and so on.”

Deciphering the complex connections between genes and diet that determine whether or not an individual develops these diseases is one of the biggest challenges for Allayee and his colleagues. “Disentangling these uncertainties is probably the most difficult thing we have to deal with,” he says. “That is why we use mouse genetics and genomics technologies such as microarrays to try and break apart these intricacies and determine what stands out once you sift through all the noise.”

He says that mouse models are essential for research because the genes between humans and mice are so similar. “If you identify a gene that causes heart disease in a mouse, you can then test that gene in humans,” he says. “Conversely, if you find genes in humans associated with heart disease you can study it in mice by making a mouse that doesn’t have the gene, or has multiple copies of the gene, so it is a combined ping-pong approach.”

As an undergraduate, Allayee was not all that focused on genetics. But one summer, he found himself working in a genetics lab, and it completely captured his attention. “The fact that you are born with these genes, and how those shape everything from your personality to your appearance to your susceptibility to disease is just fascinating to me,” he says. “It is not at the atomic level, it is on a general level, so it suits my personality because I like to look at the big picture.”

Like many of his peers, Allayee longs for the day when truly affordable high-throughput sequencing technology will be readily available. At $500 per genome, he says, “That would open up so many things, not just from a disease point of view, but from ... an evolutionary and a mutation-rate point of view,” he says.

Looking ahead

Allayee says that although several genes have been pinpointed as the cause of heart disease, the fact that none of this data means anything to current patients is frustrating. “We are going to identify more and more disease-causing genes, and that’s good for biology, but when are we going to find a drug or treatment and how can we translate these genetic findings to keeping people from having heart attacks?” he says.

“What I would like to do is to take things that we find and translate them to therapies that somehow help someone to not have a heart attack.” He says the solution will involve partnerships with pharmaceutical companies and a broader understanding of how drug targets and pathways work together to cause disease.

Publications of note

In 2004, Allayee published a landmark paper in the New England Journal of Medicine entitled “Arachidonate 5-lipoxygenase promoter genotype, dietary arachidonic acid, and atherosclerosis,” which he says helped land him his first faculty position. According to the study, individuals with the 5-lipoxygenase gene are susceptible to increased atherosclerosis in the carotid artery, which is associated with human heart disease. They found that increased dietary intake of arachindonic acids significantly enhanced the risk of developing atherosclerosis with individuals carrying this gene. Conversely, an increased intake of fatty acids was shown to decrease the effect of the gene.

And the Nobel goes to...

Allayee says that if he were to win the Nobel it would have to be for developing something that would allow people to do experiments in ways never before thought possible.

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