Douglas C. Wallace, a founder of the field of human mitochondrial genetics, has received a $2.25 million award from the Doris Duke Charitable Foundation to study how metabolic disorders may be triggered by genetic changes in the mitochondria, the power plants of human cells.
Using DNA samples from patients of Chinese heritage living in Taiwan and in Southern California, the study may lead to a greater understanding of the metabolic syndrome -- the risk factors behind diabetes, obesity, hypertension, high cholesterol and cardiovascular disease -- and provide new approaches to their diagnosis and treatment. Illnesses associated with these disorders have reached epidemic proportion, affecting more than 50 million Americans and creating an acute need for effective diagnostics and therapeutics.
"Our receipt of this prestigious Doris Duke Charitable Foundation award is the direct consequence of UCI's vision of becoming a world leader for the new biomedical discipline of mitochondrial medicine," said Wallace, director of the Center for Molecular and Mitochondrial Medicine and Genetics (MAMMAG) at UC Irvine and National Academy of Sciences member.
Mitochondrial medicine offers innovative new perspectives and approaches for addressing the common age-related diseases associated with the metabolic syndrome as well as with forms of blindness, deafness, movement disorders and dementias -- clinical problems that remain elusive to traditional biomedical concepts and approaches.
With the Doris Duke Clinical Interfaces Award -- which will provide funding for five years -- Wallace will lead a multidisciplinary team of UCI researchers, which include physicians Dr. Ping Wang, Dr. Lee-Ming Chuang and Dr. Jay Gargus; biomedical engineer Bruce Tromberg, director of the Beckman Laser Institute; and atmospheric chemists Donald Blake and F. Sherwood Rowland, who received the Nobel Prize in Chemistry in 1995.
The team will study genetic variation in the DNA of mitochondria and its association with the various symptoms of the metabolic syndrome. Wang, Chuang and Gargus will collect mitochondrial samples from metabolic syndrome patients of Chinese heritage in Taiwan and in Southern California. Wallace's team at MAMMAG then will conduct extensive molecular and biochemical studies of these samples to see if variations in mitochondrial DNA as well as environmental factors affect individual predisposition to the clinical symptoms of metabolic syndrome.
At the same time, Gargus and Wallace will work with Blake, Rowland and Tromberg to develop rapid, non-invasive methods to diagnose metabolic syndrome. Atmospheric chemists Blake and Rowland will use their expertise with breaking down the components of gasses to perfect a breath-analysis system that can evaluate changes in the breath chemistry of mitochondrial metabolic syndrome patients. Tromberg is working on an infrared laser system that can evaluate certain aspects of mitochondrial physiology by shining light directly into the skin.
"By correlating the results of these cutting-edge technologies with those of MAMMAG's molecular and biochemical analyses, our consortium hopes to not only extend our knowledge of the role of mitochondrial defects in the metabolic syndrome but to perfect simple non-invasive diagnostic tools that will permit the rapid identification of mitochondrial patients within the doctor's office," Wallace said.
Mitochondrial samples from Southern California patients of Chinese heritage will be taken at UCI Medical Center in Orange. Wallace's group is one of three teams in the U.S. to receive the 2005 Doris Duke Clinical Interfaces Award, and was chosen from more than 100 proposals. For more information on metabolic syndrome from the American Heart Association, go to www.americanheart.org.
Wallace, the Donald Bren Professor of Biological Sciences and Molecular Medicine and one of the world's leading geneticists, has worked in the field of human mitrochondrial genetics since the 1970s. He is the author of more than 230 research papers, many of which have appeared in leading journals. Highly honored for his research, he received in 1994 the William Allan Award, the American Society of Human Genetics' highest recognition for contributions to human genetics. He also has shared the 2000 Passano Award for mitrochondrial genetics and received the 2000 Metropolitan Life Foundation Research Award for Medical Research in Alzheimer's Disease.
Derived from early bacteria living in the first plant and animal cells, mitochondria are found in human cells and generate most of our energy. They contain their own DNA, which contains key blueprints for maintaining these cellular power plants. Defects in the power-plant blueprints result in the cellular equivalent of a brownout, thus creating systemic energy deficiency that leads to localized functional failures. These blueprints are inherited exclusively from the mother.
Wallace and his associates have already linked mitochondrial defects to a wide range of age-related disease symptoms and have shown that mild alterations in the mitochondrial DNA blueprints were critical for our ancient ancestors to adapt to their to colder northern latitudes as they moved out of Africa into temperate and arctic Eurasia. Today the same adaptive variants are affecting how individuals manage and utilize the calories in our food, thus affecting predisposition to the symptoms of the metabolic syndrome.
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About MAMMAG: The Center for Molecular and Mitochondrial Medicine and Genetics brings together basic scientists, clinical investigators and patients at UCI to determine the causes of the common degenerative diseases, cancer and aging, with special emphasis on the role of mitochondria in these diseases' processes. The result is a uniquely integrated, multidisciplinary research and clinical program that intends to expand the horizons of medical understanding. For more information, call (949) 824-3490 or e-mail firstname.lastname@example.org.
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