Coalition joins diabetes battle

[Source: Joe Caspermeyer, Biodesign Institute] -- A new team of researchers from ASU and the University of Arizona is taking aim at the sixth-leading cause of death in the United States: adult-onset, or type 2, diabetes. The coalition’s goal is to learn how to predict who will develop the disease long before any symptoms appear.

“Right now, current indicators – biomarkers – of type 2 diabetes are not well-defined, and most such markers are only reliably detected in people who have already been diagnosed with the disease,” says Serrine Lau, a professor at UA’s College of Pharmacy and a member of the BIO5 Institute. “Finding these clues, which will allow for the early treatment and possible avoidance of the complications associated with the disease, is the goal of our research.”

The principle researchers on the project include UA’s Serrine Lau, George Tsaprailis and Craig Stump; Randy Nelson and Mike Mobley from ASU’s Biodesign Institute; and ASU kinesiology chair Larry Mandarino, who directs the Center for Metabolic Biology in the College of Liberal Arts and sciences.

Lau spearheads the team’s investigation using cutting-edge technologies to discover and validate new biomarkers to detect pre-type-2 diabetes. It is a collaborative project between UA’s BIO5 Institute and ASU’s Biodesign Institute supported by the Technology and Research Initiative Fund (TRIF). TRIF is a special investment in higher education made possible by passage of state Proposition 301 in November 2000.

“Our project is unique in the country,” Lau says. “First, collaborations between our two groups of experts enable us to combine exceptional intellectual and technological resources to address the problem. Second, we are conducting a highly targeted discovery investigation, which is guided by very well-defined clinical protocol. Third, we have a broader patient sample. Similar projects elsewhere are investigating patients who have already been diagnosed with diabetes, but we are looking at a more random sample of the population, and trying to learn how to predict who will develop diabetes.”

“We have the technologies and tools in place now to construct a detailed molecular signature of diabetes,” says Randy Nelson, who heads the Molecular Biosignatures Analysis Unit at ASU’s Biodesign Institute. “By studying the changes in both the expression and structure of proteins related to diabetes, we can determine their contribution to the disease process.”
Nelson is an expert in proteomics, a scientific discipline that studies changes in protein composition – generally in biofluids such as blood and urine – and how these changes relate to disease.

“With the completion of the human genome project, we now understand that genomics alone is insufficient to fully understand cellular biochemistry,” Lau says. “It is the proteins that are the workhorses in regulating biological events.”

Researchers use state-of-the-art technology, including protein sequencing by mass spectrometer, which is an instrument used to determine the composition of a physical sample by generating a spectrum representing the masses of sample components. The BIO5/Biodesign team uses mass spectrometers to identify proteins and their functional states, as well as to measure the quantity of particular proteins. For example, someone with a disease may be producing too much of a given protein that would normally be present in lower amounts in a healthy individual.

“As a clinician treating diabetes, this research is particularly exciting,” says another study participant, Craig Stump, chief of the section of endocrinology, diabetes and hypertension at the UA College of Medicine. “We’ve always used a ‘shotgun approach’ to preventing diabetes – we know we have been overtreating some people and undertreating others. Knowing a patient’s individual risk for diabetes will allow physicians to offer highly specific recommendations to avert the disease. It’s going to change lives.”

“The investigation is challenging, overarching and sometimes it can be intimidating,” Lau says. “But we now realize that it is the path we have to take. It is essential that we approach this in a cooperative and global manner.”