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Ronald M. Evans

 

Ronald M. Evans

Ronald M. Evans

Professor and March of Dimes Chair in Molecular and Developmental Biology
Gene Expression Laboratory

"Our lab is interested in understanding the molecular genetics of metabolic disease and inflammation, including atherosclerosis and diabetes as well as cancer, and using this information to devise cures for their treatment. By tinkering with a metabolic program in muscle, we stumbled upon 'exercise in a pill.'"

Previous work with genetically engineered mice in the Evans lab had revealed that permanently activating a genetic switch known as PPAR delta turned mice into indefatigable marathon runners. In addition to their super-endurance, the altered mice were resistant to weight gain, even when fed a high-fat diet that caused obesity in ordinary mice. On top of their lean and mean physique, their response to insulin improved, lowering levels of circulating glucose. Wondering whether a drug specific for PPAR delta could have the same effect, Evans and his colleagues began testing an investigational PPAR delta compound only known as GW1516.

When they fed the substance to laboratory mice, fatty acid and blood glucose levels started to drop, yet there was absolutely no change in exercise performance. Undeterred, they put mice on treadmills and then gave them GW1516. After only four weeks, the exact same drug that had shown no effect in sedentary animals improved endurance by 77 percent over exercise alone. This stunning result gave rise to a vexing question: Why is exercise so important? Exercise depletes muscles' energy store, a chemical known as ATP, activating AMPK, a metabolic master regulator. AMPK then directs the muscle to burn sugar and fat to replenish ATP. The researchers' experiments revealed that some exercise-activated AMPK molecules slip into the nucleus. There they physically interact with PPAR delta and increase its ability to turn on the genetic network that increases endurance. In the ultimate couch potato experiment, they asked if a drug known to activate AMPK could actually mimic exercise. After only four weeks, the treated mice got up and ran 44 percent longer than untreated, untrained mice.

In addition to their allure for endurance athletes, drugs that mimic the effects of exercise have therapeutic potential in treating certain muscle diseases, such as wasting and frailty, obesity, and a slew of associated metabolic disorders where exercise is known to be beneficial, as well as aiding hospital patients unable to exercise and veterans and others with disabilities.

Lab Photo

Left to right:
1st Row/standing: Li Tai, Ann Atkins, Sungsoon Fang, Emi Embler 1st Row /seated: Han Cho, Sally Ganley, Samantha Kaufman, Katja Lamia, Erin Dunn, Yuhua Zou, Thomas Sternsdorf 2nd Row: Jackie Moran, Yungqiang Yin, Yihong Wang, Liming Pei, Ming XiaoHe, Xuan Zhao, Tao Li, Ankang Li, Hans Jonker, Ron Evans, Ruth Yu, Lita Ong, Michael Downes, Jackie Alvarez, Elena Caceres, ChungLi Zhang, Xiaoyong Yang, Ester Banayo 3rd Row: Henry Juguilon, Sukhyon Hong, Kazuko Kawamura, Corrine Ocampo, Shigeki Sugii, Grant Barish, Vihang Narkar, Colin Phillips, Jaime Whyte, Jesse Dixon, Russell Nofsinger, Mike Nelson

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Ronald M. Evans

Faculty

Ronald M. Evans

Ronald M. Evans

Professor and March of Dimes Chair in Molecular and Developmental Biology
Gene Expression Laboratory

Ronald M. Evans, a professor in the Gene Expression Laboratory, is the March of Dimes Chair in Developmental and Molecular Biology. Evans is an authority on hormones, both their normal activities and their roles in disease. A major achievement in Evans' lab was the discovery of a large family of molecules, named receptors, that respond to various steroid hormones, Vitamin A and thyroid hormones. These hormones help control sugar, salt, calcium and fat metabolism; thus, they impact on our daily health as well as treatment of disease. The receptors Evans discovered are primary targets in the treatment of breast cancer, prostate cancer and leukemia, as well as osteoporosis and asthma.

In addition, Evans' studies led to a new hormone that appears to be the molecular trigger controlling the formation of fat cells. This hormone and its chemical derivatives represent one of the newest and most important advances in understanding problems arising from excess weight and obesity and the potential treatment of adult onset diabetes (Type II diabetes).

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