Robert Haile
Robert Haile's scientific mission is simple: seek and find the genetic and environmental causes of cancers in order to protect those of us at risk.
Robert Haile, Dr.P.H., is a scientist with the eye of a photographer and the soul of a poet. As a college student, he chose to study international health, "thinking I'd be in Africa now, driving a Range Rover." But instead of bouncing along on the savanna, Haile lives and works in Los Angeles, amidst palm trees and convertibles. And instead of battling epidemics in the field, he is battling one of the greatest epidemics of them all-cancer-from one of the nation's cancer command posts: an impressively neat office at the USC/Norris Comprehensive Cancer Center lined with artwork done by his young son.
And, he says unabashedly, he loves it.
"I came here to join the best cancer epidemiology group in the world," he declares. "I may not have planned it this way, but I have no regrets."
Africa's loss is clearly USC's gain-not to mention the gain of cancer patients worldwide. In the nearly six years he's been at the USC/Norris, Haile, a professor of preventive medicine, has compiled a remarkable body of work.
He has:
helped provide strong evidence that taking calcium supplements can ward off colorectal cancer (his group is now funded to unlock the mechanism responsible for this protection);
helped uncover the genes that are linked to an increased risk of developing colon cancer by interacting with selected environmental exposures;
shown that taking beta carotene and vitamins C and E do not protect against colorectal polyps, as had been previously thought; and
continued to head up development of a registry of families at high risk of developing colorectal cancer.
That latter project, called the Cooperative Family Registry for Colorectal Cancer Studies, is "the largest single database for colorectal cancer in the world," says Haile. Coordinated by USC, the project is a consortium along with five other independent U.S. institutions. To date, the registry has collected data on 11,000 families around the globe, all of which have at least one case of colorectal cancer amongst their members-and 60 percent of which have multiple cases. With this much data, says Haile, gaining insight into the genetic roots of this complex and lethal disease becomes not only possible, but also probable. "Our main mission," he explains, "is to find the genetic and biochemical causes of colorectal cancer, then design prevention trials to begin to protect those at risk."
Haile's personal scientific mission is quite similar. "What I'm trying to do here," he explains, "is to understand what causes any number of cancers, with the hope that this will allow us to find ways to prevent them from developing in the first place. And, to me, the key to doing that is realizing that cancers have both genetic and environmental causes-and looking at them together."
This, says Haile, is not as obvious as it may seem. "We are one of the first groups to have taken seriously the interface of genes and environment," he says. "In the past, most genetic studies have tended to ignore or discount environmental influences, and environmental studies have ignored the genes."
Not so Haile and his colleagues. For instance, the group that he directs, the USC/Norris Genetic Epidemiology Program, and frequent collaborator John A. Baron, M.D., of Dartmouth University, have been looking at the roles of aspirin and folic acid-together and separately-in decreasing the risk of colon cancer. "Aspirin has a very strong effect," says Haile. "Our very promising preliminary data shows consistent evidence that taking aspirin decreases the risk of colon cancer by half." Haile has collected similarly promising data on folic acid.
But that, he says, is only half the story. The other half is the way in which these outside influences might be working to accomplish the risk reduction-by protecting key genes from changes that might otherwise kick a cell into a cycle of unchecked growth and proliferation, the hallmark of malignancy. "For example, folic acid may be involved in methylation," he explains. Methylation is the chemical process by which a methyl group is added to a compound. Too much methylation, known as hypermethylation, is thought to play an important role in the pathogenesis of cancer. "And so folic acid may be working to reduce hypermethylation in genes that might otherwise produce colon cancer." Pinning down just how they keep control over these processes might allow researchers to find or create drugs that would be even more targeted, and even more effective at keeping cancer at bay.
Similarly, assistant professor Victoria Cortessis, Ph.D., and Daniel Levy, Ph.D., professor of biochemistry and molecular biology, are working with Haile to investigate a particular gene/chemical interaction. They are studying the ways in which a gene - microsomal epoxide hydrolase (mEH) - interacts with chemicals - polycyclic aromatic hydrocarbons (PAHs) - that are commonly found in cigarette smoke or in foods like well-done red meat. "It's a perfect example of the ways in which genes can convert or detoxify exposures in their environment," says Haile. "In this case, at least in animal models, it has been shown that when mEH converts or metabolizes the PAHs, it can turn them into very strong carcinogens." Knowing this, the search is on for ways to either reduce the amount of PAHs we take in, or to block mEH from turning them into carcinogens.
In addition, researchers looking to interfere with this cancerous cycle can look to other genes as well. "[Humans] also carry genes that work to detoxify potential carcinogens, rather than create them," observes Haile. Finding these and amplifying their effects might make up for the destruction wrought by genes like mEH. "It's understanding the interplay between the genes and the environment that can help us either block or enhance these interactions."
Colon cancer isn't Haile's only target. He is also interested in the interplay of genes and environment in the pathogenesis of breast cancer. He was recently awarded a grant by the National Cancer Institute (NCI) to head up a major investigation into the connection between a degenerative nerve disease called ataxia telangiectasia (AT) and breast cancer. People with AT, which is a recessive genetic condition requiring two mutated versions of the gene in question, are "exquisitely sensitive" to radiation, says Haile. There is some thought that people with only one copy of the AT gene (heterozygotes) who do not actually exhibit the disease's symptoms-might also be somewhat sensitive to radiation as well.
How might breast cancer and AT be connected? If AT heterozygotes are indeed more sensitive to radiation, as research done elsewhere seems to suggest, the current recommendation of yearly mammograms for women over 40 could be raising the risk of breast cancer significantly for women who carry the AT gene. "If this turns out to be the case," says Haile, "we may need to rethink the mammogram recommendations in this subgroup of women."
That is why the NCI study will look not only at radiation sensitivity in these women, but also at whether their breast cancer risk is higher-and if so, by how much. And to do this, Haile and his University of California, Los Angeles collaborator Richard Gatti, M.D. -a renowned expert in AT-will coordinate the collection of data from 700 families affected by AT across seven countries, including the U.S., Canada, Costa Rica, Italy, Israel, Germany and Turkey.
It is just this sort of collaboration-a coordinated effort to look at a scientific problem from all possible points of view-that satisfies Haile's creative soul. Genetic epidemiology may not seem to have much in common with photography and poetry, but make no mistake about it: Robert Haile is a true master of the fine art of investigating cancer causes.