Illinois Medicine

Biochemist Mary Jo LaDu, PhD, has spent two decades researching the risk factors for Alzheimer's disease— most particularly the reasons why apoE4, one of three variants of the apoE gene, is the disease's most significant genetic risk factor, making a patient 15 times more likely to contract Alzheimer's. She has developed biomarkers and an animal model that could revolutionize drug development. very good markers for progression of the disease," she says. "Translational science has always been part of what we do, in that if you don't go back and ground your observations [from animals] to what's going on in humans, what are you chasing?" LaDu's approach also illustrates that academic translational research can attract young researchers who might otherwise prefer industry. For example, postdoctoral fellow Leon Tai, who has a background in drug discovery, joined LaDu's team, enticed by the potential that her research "will ultimately identify the mechanisms underlying apoE4-induced Alzheimer's risk." Gregory Thatcher, PhD, professor of medicinal chemistry and pharmacology at the College of Pharmacy, is using LaDu's transgenic mice in his research that tests therapeutic agents targeting Alzheimer's. "The real advantage of [her] model is that it incorporates apoE4, the major genetic risk factor for Alzheimer's disease, associated with 50 percent of patients over 85 years," he says. "In addition, apoE4 patients often display a differential response to therapeutic treatments." A t the college's Sickle Cell Center, Gordeuk says his team of researchers, clinical and basic, has melded into a seamless whole that attacks the disease from both directions. Clinical observations in patients prompt basic research that, in turn, drives the development of new treatments for the wide array of symptoms that sickle cell disease patients have to endure. Gordeuk, who began his career at a rural mission hospital in Africa, observes that translational research has taken him from the P h o t o : R o b e r ta D u p u i s - D e v l i n clinic back to the bench. "We've gotten more involved in genetics and lab-based research," he says. "Translational science builds on observations in patients that give you insights into what you should be working out at the basic level." Sickle Cell Center researchers, for example, are studying how the disease affects the cardiovascular system and leads to often deadly pulmonary hypertension. They also are investigating the way patients perceive pain and the pathways of the excruciating, sometimes dayslong bouts of pain they suffer. "There's research done in the laboratory at the cell culture level looking at pathways in cells, research done at the genetic level looking at expression of genes and the association of genes with symptoms and complications," Gordeuk says. "That's basic science intersecting with clinical problems the patients have. Likewise, the problems patients have are what are driving animal models in cell biology. " Gordeuk is the principal investigator of a clinical study involving an agent that may prove useful for treatment of acute pain crisis in sickle cell disease, and the center is involved in multisite studies, some supported by the NIH, some by small drug companies like Emmaus, Glycoimetics and HemaQuest, to develop treatments to prevent sickle cell's many complications, such as chronic pain and organ damage. As part of the college's section of hematology and oncology, the Sickle Cell Center stresses collaboration with numerous faculty members. "We have a really broad approach to treatment of the disease," Gordeuk says. "We'd like to make real contributions to solving the problems of sickle cell disease." Patients like Gloria Johnson, 58, heap enthusiastic praise on the Sickle Cell Center. "I don't know what I would do without the illinois medicine | 27

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