Round I Research Awards

• Alzheimer's disease
• Prostate cancer
• Obesity
• Cardiovascular Disease

Alzheimer's Disease Team

The ground-breaking work on Alzheimer's disease by researchers Joseph Poduslo, Ph.D., Mayo Clinic, Clifford Jack, M.D., Mayo Clinic and Michael Garwood, Ph.D., University of Minnesota, illustrates perfectly the symbiotic relationships inherent in the Mayo Clinic/University of Minnesota research teams.

Alzheimer's is the fourth leading cause of death for those over 65. By the year 2040 an estimated 14 million will be living with the disease. One of the cardinal pathologic features of the disease is the formation of both senile and amyloid plaques (basically protein deposits) in the brain. Until recently, these plaques were too small to see, so precise diagnosis of Alzheimer's disease could occur only at autopsy or with the use of cognitive testing that is influenced by many other issues in the patient's life, often making it inaccurate. This is one of many reasons that the disease is so perplexing. But the Alzheimer's disease team of the Minnesota Partnership for Biotechnology and Medical Genomics has discovered a way to view amyloid plaques in vivo (in a living specimen), setting the stage for early diagnosis and therapeutic steps before dementia occur.

Half of this finely tuned scientific team lines a quiet corridor in the Guggenheim Building in Rochester where Dr. Poduslo and his team operate what is best described s a scientific production line. Experts in protein analysis and synthesis, are preparing proteins and adding contrast agents to make the proteins visible. Dr. Clifford Jack steps in as the expert in post imaging analysis and MRI and a renowned expert in Alzheimer's Disease. Next door, Thomas M. Wengenack, Ph.D. and Geoffry L. Curran are responsible for raising, breeding, genotyping, and physiologically monitoring the transgenic mice that are such a critical component of this work. Two hours away in Dr. Garwood's lab at the University of Minnesota, behind a large glass window hums one of the largest, most complex MRI machines. Dr. Garwood designs the pulse sequencing for the imaging that determines the length and timing of the pictures, and he operates the MRI. His expertise in scientific software, graphics and imaging is critical to getting perfectly timed, accurate pictures.

All of these steps take experts in specialized areas of medical research including pharmacokinetics (the distribution of materials throughout the brain and body), neurology and neuroscience, radiology, genomics, biochemistry, molecular biology, surgery and, of course, Alzheimer's Disease. The level of expertise here is clear to the observer, but so is the comfortable working environment of this team. There is great mutual respect and admiration, but also ample laughter and joking to offset the intensity of their research.

It's hard to believe that the complex research of this team takes place in laboratories two hours apart, but in fact, the flow of the research and the interaction between team members is seamless. "We constantly talk by telephone and e-mail all day - we probably communicate more than people who work at the same site! We also spend every Wednesday together, traveling between Mayo and the University." Working as if their labs were doors apart, each lab and investigator offers their scientific expertise by conducting very specific parts of the research.

Doctors at Mayo believe that medical research is advanced far more by teamwork than by an individual working alone. The diversity and excitement of the Minnesota Partnership's Alzheimer's team is a 21st Century example of that belief.

To read more about the research of the Alzheimer's Team, go to www.mayo.edu or discoverysedge.mayo.edu.

The Alzheimer's Disease Partnership team has published their findings in the Proceedings of the National Academy of Sciences [Marjanska et al. (2005)102, 11906-11910.]. This marks the first publication of research funded by the Partnership. The researcher team notes that their techniques in high resolution imaging analysis of mice with Alzheimer's like plaques could speed efforts to find new drug therapies for Alzheimer's disease. To read the full press release, please click here

Prostate Cancer Team

Prostate Cancer Team: Donald Connelly, M.D., U of M; George Klee, M.D., Ph.D., Mayo Clinic.

Coordinated Multi Program Utilization of Microarray Data to Generate and Validate Biomarkers for Improved Care of Patients with Prostate Cancer

The focus of this effort is discovery. By looking at frozen tissue samples from men who had prostate cancer, researchers are looking for genes that are present in aggressive forms of cancer and early detection. Using the combined expertise in bioinformatics at both the University and Mayo Clinic and the large number of patient samples at Mayo, the two institutions are studying different forms of prostate cancer stages to see if there are blood components they can test for that would indicate a tumor's presence and aggressiveness and identify certain markers that will indicate not only that the patient has cancer, but what kind of cancer.

Physicians can use simple blood tests, such the level of PSA (prostate-specific antigen) to identify prostate cancer, but these carry the risk of "false positives" and do not determine how aggressive the cancer is. A non-invasive blood test for prostate cancer that determines how aggressive the cancer is would help physicians choose between "watchful waiting," a very effective strategy for many prostate cancer cases, and aggressive treatment.

Researchers in this study are looking for such a test in the form of a panel of new biomarkers - chemical and genetic tracers - that will lead to specialized prostate cancer tests that can be performed on blood samples or biopsy tissues. Mayo researchers are using a laser beam to isolate specific, malignant cells from tissue samples of men who had prostate cancer. Once isolated, the messenger RNA is extracted from thousands of cells specific to prostate cancer and then amplified using a technique called linear amplification. Then, research measurement systems and specialized bioinformatics programs are used to identify possible biomarkers in the samples. The end product shows which genes are over-expressed. Scientists hope to create improved and more specific chemical or genetic tests for prostate cancer that will identify the more aggressive forms of the cancer.

This discovery stage will be followed by what researchers call validation, which is as challenging as the discovery stage in new drug development. Validation is a gene-by-gene confirmation of the discoveries they made. It is then that researchers can move the process from the laboratory to clinical trials to confirm how well such a method works in patients with prostate cancer.

Obesity Team:

Obesity Team: Catherine Kotz, Ph.D., University of Minnesota; James Levine, M.D., Mayo Clinic

Non-Volitional Activity in Obesity Resistance: Role of the Brain

Recent studies show that more than half of Minnesotans are overweight and one in five are clinically obese. Minnesota healthcare costs related to obesity are estimated at $1.4 billion. Annually in the United States, more than 300,000 deaths are linked to obesity. This Partnership team is exploring how chemicals in the brain may make an individual naturally resistant to obesity.

Eating habits, metabolism, and exercise do not account for the obesity epidemic in the United States. Mayo Clinic researchers have found that the energy we burn up in daily activities, not the calories used while exercising, is far more important in weight control than traditional exercise. They've termed this factor NEAT - non-exercise physical activity thermogenesis. How individuals react to NEAT can mean as much as a 1,000 daily calorie difference from person to person. "Our research shows that NEAT is far more important than calorie-burning through exercise. Thus being a "weekend warrior" is not as effective as walking up stairs instead of taking the elevator, parking farther away from one's workplace, and standing rather than sitting in controlling your weight." says Dr. Levine. Researchers from the University of Minnesota have found that NEAT is likely regulated through a central mechanism, such that NEAT is activated with over-feeding and suppressed with under-feeding.

To further investigate NEAT, this Partnership team is studying neuro-chemicals in the brain that may signal when to eat or to move. Their work is beginning to shed light on the role of a protein called neuropeptide, orexin A, in NEAT. Orexin A stimulates physical activity in animals and humans, which is directly linked to NEAT, suggesting that NEAT is biologically regulated. Dr. Kotz notes "these observations imply that we can identify biologic factors that may account for variance in NEAT, and that NEAT is important to obesity."

Deciphering the role of NEAT may lead to a better understanding of the origin the pathology behind obesity, which could enable medical researchers to develop novel approaches to prevent and treat obesity in Minnesota. Still, much remains to be learned about NEAT, begging questions such as: Can we learn to burn more? Can we learn to work and live in ways that promote nonexercise activity? Are there biological mechanisms that can be modified, by drugs or other means, to produce healthier lives for people now struggling with obesity? This team's work is progressing toward answers to these and other questions.