Collaboration seeks early detection of type 2 diabetes

A new team of researchers from UA and ASU is taking aim at the sixth leading cause of death in the United States: type 2 diabetes. The coalition’s goal is to learn how to predict who will eventually develop the disease long before any symptoms appear.

“Right now,” says Serrine Lau, professor at UA’s College of Pharmacy and member of the BIO5 Institute, "current indicators – biomarkers – of type 2 diabetes are not well defined and most such markers are reliably detected only in people who have already been diagnosed with the disease. But type 2 diabetes is a genetic disease, so there are likely to be biochemical indicators in the bodies of individuals who have yet to show clinical signs of diabetes, but who will do so in the future. If we can detect those indicators now, we will know whether or not a person is likely to develop the disease. Finding that clue, which will allow for the early treatment and possible avoidance of the complications associated with the disease, is the goal of our research.” Lau


From left: George Tsaprailis, Craig Stump and Serrine Lau in the
proteomics lab at the Thomas W. Keating Bioresearch Building.

Their project, “Proteomic and Metabolomic Biomarker Investigation of Type 2 Diabetes,” is an investigation using cutting-edge technologies to discover and validate new biomarkers to accurately detect pre-type 2 diabetes. It is a collaborative effort 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.

BIO5 members who are participating in the study are Lau, who is also director of the Southwest Environmental Health Sciences Center; George Tsaprailis, director of the Arizona Proteomics Consortium, of the College of Pharmacy; and Craig Stump, associate professor, College of Medicine.

“Our project is unique in the country,” says Lau. “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.”

Proteomics and metabolomics are two fields in the science of biology. Metabolomics is the study of a collection of small biomolecules, such as sugars, fatty acids, and drug/chemical metabolites. Diabetes is a metabolic disease, so the team is interested in studying metabolic abnormality.

Proteomics is the study of a collection of proteins. It is the next step in bioscience after the mapping of the human genome. It is proteins that exert the most influence over cellular functions in the body. “With the completion of the human genome project,” says Lau, “we now understand that genomics alone is insufficient to fully understand cellular biochemistry. It is the proteins which are the workhorses in regulating biological events.”

“For many years we had the technical capability to study only a single or at best a handful of proteins. We now have the technology to simultaneously study hundreds, perhaps over a thousand proteins. Moreover, we now also realize that subtle modifications to a protein following its initial synthesis, and proteins’ ability to interact with each other, together contribute to their specific biological function. We therefore need state-of-the-art technology to study changes in both the expression and structure of proteins in order to determine their contribution to the disease process.”

This state-of-the-art technology includes protein sequencing by mass spectrometer, 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 the mass spectrometer not only to identify proteins and their functional states, but also 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.

“The investigation is challenging, overarching and sometimes it can be intimidating,” continues Lau. “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.”

Article taken from the College of Pharmacy Newsletter, August 24, 2007
http://www.pharmacy.arizona.edu/newsletter/aug2407.html

 

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